This is a summary of a talk I heard at the National Kidney Foundation Spring Clinical Meeting in May of 2024.
Speakers: Calvin Meaney PharmD, Ben Redan PhD, Desiree de Wall RD
Objectives:
- Drug and herb interactions
- Pharmacology of commonly used herbal supplements in nephrology
- Evidence-based resources to identify herb-drug interactions
Of note, KDIGO 2024 recommends avoidance of herbal products.
How do herbs interact in the body?
If two drugs or a drug and herb combine then this can impact how both substances behave.
Example: The medication cyclosporine is absorbed in the gut and couples with p-glucoprotein. It then travels to liver where it interacts with CYP-3A4 and is pumped out systemically. St-Johns wort increases p-glucoprotein and CYP-3A4 action. This dramatically increases the systemic exposure of cyclosporine and can lead to organ rejection.
Other known interaction examples:
- Apixaban + ginko biloba = increased bleeding.
What other considerations may be needed for herbal supplements?
Some supplements can be higher in potassium and phosphorus. Products that tend be leaf based (e.g. dandelion leaf) can be very high in potassium.
What is one of the most problematic herbal supplements?
One of the highest herbal supplements that post risk for herb-drug interactions is St. John’s Wort. St- John’s Wort has been used for antidepressant, anxiolytic, insomnia and menopause. It’s mechanism of action is augmentation of both CYP3A4 and p-glycoporteins. MANY MANY drugs also use this pathway.
What is the concern with herbs that have diuretic properties?
Herbs that have diuretic effects can act synergistically with medications for diuretics and could induce dehydration and AKI.
What bleeding risk related herbs should we be aware of?
Can use the 5G pneumonic: Ginseng, ginger, Gingko biloba, Garlic and Grapefruit. These five herbs are known to be high risks for inducing bleeding risks.
What safety concerns have been reported with regards to herbal products?
- There have been reports of microbial contamination of some herbal products
- 50% of products contained ingredients that weren’t on the label
- Some herbal products were found to contain heavy metals
Is there something we can recommend to help keep our patients safe if they want to take herbal supplements?
A key thing to encourage patients is to look for products with a third party verification. Third party verification means that a third party has reviewed the products for:
- Confirmation that what is listed on the label is true
- Doesn’t contain contaminants
- Will be absorbed
- Made inline with good manufacturing practices
There are two bodies in the US that offer third party verification. In Canada, I think of this as akin to recommending a product which carries an NPN (or natural product number).
What resources can we use to look up information about herbal products?
- Memorial Sloan Kettering Database – About Herbs Database. Initially created for cancer however it can also be used in kidney care
- Natural Medicines Database
- National Center for Complementary and Integrative Health
- This one wasn’t mentioned in the talk, but if you are Canadian, this is another database I like to use: The Natural Health Product Database (Canadian Government Database)
What regulations are in effect for dietary supplements (in the USA)?
Dietary supplements were first covered under an act in 1994. The point of this law was ensure consumers would have access to safe products. Dietary supplements are regulated under a category of foods, vs medications which are under pharmaceutical.
What are companies making supplements obligated to do?
Under law, companies that make supplements are required to:
- Registration facility
- Notify the FDA of new dietary ingredient
- Comply with labeling laws
- Produce products inline with established good manufacturing practices
- Report adverse events
Though it is important to note that the onus of compliance is on the company and not the FDA.
How are dietary supplements identified?
If a product is being marketed as a dietary supplement, it must state that it is. It must include a dietary supplement facts label.
What is not a dietary supplement?
Conventional foods (e.g. protein powder – will then have a nutrition facts label) or OTC drug products (e.g. acetaminophen – will then have a drugs facts label)
What claims can dietary supplements make?
- Structure or function claims – These are claims on how it augments normal body functions. There is no FDA approval for this claim and they must include a disclaimer about this. However companies must submit a claim notification to the FDA. The literature supporting this claim is not investigated by the FDA
- Health Claims – the relationship between a substance and its ability to reduce disease risk. This is reviewed by the FDA and requires scientific evidence. An example is claims on calcium which can claim that it reduces the risk of osteoporosis.
- Disease Claims – these do not fall under the provisions of the dietary supplement act. For example a product can not make a claim that it protects against the development of lung cancer. These types of claims are not permitted on dietary supplements. This is because this type of claim would fall under the jurisdiction of a drug.
- For example, one firm had on their website that celery seed could help with kidney failure. In this case a warning letters was issued from the FDA.
Is there anything that can be done if see a product that may be making a disease claim?
Healthcare professionals or consumers can contact the FDA to let them know about these claims. The FDA will then investigate this.
How many people are using supplements?
According to NHANEs 57% of people take supplements. Women are more likely to use them then men. 70% of Adults over the age of 60 use 1 or more supplements. And a third of those are taking 4 or more.
Less than 40% of the general population meets their micronutrient requirements, including those who live with kidney disease. People who use supplements are more likely to be seeking wellness and are interested in doing something beneficial to their health.
Are renal vitamins still recommended?
Latest evidence does not support routine use of renal vitamins in the CKD population (Wang et al AJKD 2023; 83:3). There is very little research on supplements in the CKD population.
