Mrs. M presented with a list of 20 natural supplements that she was taking to boost her immune system and fight off a lingering fatigue attributed to Lyme disease. She was in nephrology clinic to evaluate a 30% decline in kidney function over the recent 3 months.
She got straight to the point. “Are the supplements hurting my kidneys?” The best answer I could come up with was: “Maybe”. Which led to a discussion about why side effects can happen with herbal or other dietary supplements:
- Metabolism of any drug or supplement involves several enzymatic pathways. Due to genetic variability, an individual may not be able to metabolize a certain supplement, and accumulation of byproducts leads to off-target effects. As an example, the “Asian flush” after alcohol intake is due to deficiency of acetaldehyde dehydrogenase, a key enzyme needed to break down booze in the body. The resulting acetaldehyde accumulation causes facial redness, headache, and heart palpitations.
- Supplements contain more than just the pure natural product. Excipients (inactive ‘other ingredients’) are added to serve as filler, flavoring, coating, preservative, etc.1 The inactive ingredients would typically pose little to no health risk, however, again due to genetic variability some people experience side effects. For example, potassium sorbate is sometimes used to prolong the shelf life of herbal products; sensitivity to this compound induces nausea and stomach cramps.
- The optimal beneficial dose of many natural supplements is unknown. Any supplement taken in excess will overwhelm metabolic pathways and result in toxicity. Of note, many herbal products evolved as plant defenses against being eaten by insects or animals,2 thus large amounts can be viewed as natural poisons.
- In the setting of liver or kidney disease, byproducts can accumulate and cause adverse effects.
- Interactions with prescribed medications can be problematic. One example is St. John’s wort which is consumed for its anti-anxiety and anti-inflammatory properties; this herb is known to inhibit warfarin and thus increases clotting risk in patients on warfarin anticoagulation.
The use of herbal supplements is growing. In a national U.S. survey of approximately 26,000 people, more than one-third of respondents reported using herbal supplements.3 Older age and higher education were associated with higher use of herbal supplements.
Even vitamins or minerals, when over-supplemented, can cause problems. The recommended daily vitamin C intake is 90 mg for men and 75 mg for women; these needs are easily met by a balanced diet. Many people take vitamin C (usually 1000 mg daily) to boost the immune system. Vitamin C supplementation in men is associated with increased kidney stones,4 likely due to increased urine levels of oxalate (a metabolite of vitamin C) and formation of calcium oxalate stones. Vitamin D calcium combination supplements, commonly taken for prevention of bone fractures, are also associated with increased risk of kidney stones5 as high body calcium levels leads to high urine calcium. It is interesting to note that the prevalence of kidney stones in the U.S. increased from 1 in 20 persons to 1 in 11 persons in the past 2 decades (NHANES data from 1994 and 2007-2010).6 One wonders if this trend is partly driven by use of vitamin and mineral supplements.
Research is ongoing to examine how natural supplements can be used to derive health benefits without causing harm. For example, our group and other researchers are investigating the antioxidant effects of curcumin derivatives (from the spice turmeric) in kidney disease.7 Studies in cancer cell lines discovered that curcumin at high concentrations has a paradoxical effect of increasing oxidative stress (overwhelming the antioxidant benefits), emphasizing the importance of correct dosing to avoid harm.
So what is the best approach if you have decided to take a natural supplement? Definitely let your doctor know so that the medication list is checked for potential interactions and blood tests can be monitored (if necessary). Avoid taking amounts in excess of the manufacturer’s instructions. If you have chronic kidney disease, herbal supplements should be avoided per National Kidney Foundation recommendations8 (until more data is available) given concerns for high potassium or phosphorus content, diuretic effects, or direct kidney toxicity.
In the case of Mrs. M, she decided to quit the 20 natural supplements and her kidney function returned to normal a few weeks later.
1. Natural Healthy Concepts blog on inactive ingredients in supplements (2014).
2. Advances in Nutrition review paper about herbal extracts that evolved as plant defenses against herbivores and insects (2011).
3. Journal of Patient Experience report on prevalence of herbal supplements use in the U.S. (2017).
4. JAMA Internal Medicine report of increased kidney stones in Swedish men taking vitamin C supplements (2013).
5. JAMA meta-analysis noting increased incidence of kidney stones in persons taking vitamin D with calcium (2018).
6. European Urology article reporting increasing occurrence of kidney stones in the U.S. from analysis of National Health and Nutrition Examination Survey data (2012).
7. PubMed list of published research papers about curcumin effects in kidney disease (as of April 2018).
8. National Kidney Foundation website advising against use of herbal supplements in chronic kidney disease patients (2015).
Wei Ling Lau, MD is Assistant Professor in Nephrology at University of California-Irvine, where she studies vascular calcification and brain microbleeds in chronic kidney disease. She is currently funded by an AHA Innovative Research Grant, and has been a speaker for CardioRenal University and the American Society of Nephrology.