Focal Segmental Glomerulosclerosis: A Naturopathic Perspective
by Dr. Jenna C. Henderson
(Appeared in our June 2013 issue)
Dr. Henderson's response follows Dr. Hecht's letter.
Letter to the Editor
RE: 'Focal Segmental Glomerulosclerosis: A Naturopathic Perspective'
by Dr. Steven Hecht
To Dr. Jenna C. Henderson:
In the Townsend Letter June 2013 issue (page 18), Dr. Collin comments: " … patients having transplants must not be given herbal therapies." I was quite surprised to see that kind of global statement from Dr. Collin. As it turns out, he was giving a brief synopsis of your article ("Focal Segmental Glomerulosclerosis: A Naturopathic Perspective") in the same issue, wherein on page 65 you state: "Please note that Ganoderma is not safe for transplanted kidneys and all herbal medications should be presumed unsafe for transplants until proved otherwise." (my emphasis) While on the face of it this is an appropriately cautious stance, I am concerned that its generically prohibitive tone will favor interpretations – as it did in Dr. Collin's case – to an unnecessarily restrictive practice among physicians. (I realize that your article was not intended to focus on natural therapies for transplant recipients.)
Although I do not treat transplant patients as a chiropractic physician, I have 30 years of experience using herbs and supplements with my own successful kidney transplants. Having closely monitored my transplants through laboratory tests over that time, I have never seen an adverse reaction from any of the herbal/nutritional therapies that I've used – and I've used many. (I do not use medicinal mushrooms.) Having said that, an N of one doesn't mean very much. But, given proper monitoring of immunosuppressant medication levels, kidney function, and liver enzymes, I don't see the justification for saying that all herbal therapies must not be used or should be presumed unsafe for transplant recipients.
In our correspondence, you stated, "Most of the herbs I've researched will increase Il-2 with a few exceptions like garlic and green tea which decrease Il-2. As transplant medications work by downregulating Il-2, herbal preparations have the potential to undo the immunosuppression." Yet in their 2006 review article, Spelman et al. found that a majority of the herbs studied depressed Il-2 activity.1 These studies are still in their infancy. As you know, herbs often work as multifunctional immune modulators rather than unidirectional immune stimulators or depressors. For instance, Agaricus blazei Murill has such strong immune-stimulating properties that it is used to treat HIV/AIDS, but also anti-inflammatory properties so that it is also used to treat arteriosclerosis and hepatitis. I am concerned that early isolated studies looking only at the effect of a particular herb on a particular cytokine may present a misleading picture of the herb's full range of immunological effects. It would be unusual for an herb to affect only one cytokine; individual herbs in Spelman's article are found to increase or decrease both pro- and anti-inflammatory cytokines. I think we need to be careful when designating any single herb as "pro-" or "anti-inflammatory"; it seems that most herbs will have a bilateral effect and will sustain their immunological effects through modulation and systemic balancing rather than through unilateral stimulation or depression.
There is also the issue of physiological strength. Back in the early 1980s at NCNM, we were given a rough algorithm that reflected generic physiological potency levels: pharmaceuticals>herbs>foods. Because a multifunctional, multiconstituent herb is found to stimulate a certain pro-inflammatory cytokine, how much do I need to worry about intake of that herb if I'm on an intensive immunosuppressive regimen of mycophenolate mofetil, tacrolimus, and prednisone targeted to suppress pro-inflammatory cytokine activity? In my opinion, it would be like trying to light a match in a rainstorm. (If we presume that herbs and supplements have roughly the same degree of physiological potency as do pharmaceuticals, then we must agree to submit them to the same FDA protocols used to establish safety and efficacy before marketing them.) My hypothesis is that patients with glomerulonephritis in their native kidneys who are not on immunosuppression are at greater risk from imbibing pro-inflammatory herbs and foods than are transplant patients taking powerful immunosuppressants.
Many transplant patients suffer from comorbidities such as (pre-)diabetes and hypertension and could benefit from using herbs instead of pharmaceuticals to ameliorate those conditions – and many patients would prefer to do so. Diseases such as hypertension and diabetes are known to increase the likelihood of chronic rejection and should be treated in the safest and most effective way possible – and these safe and effective treatments often include herbal medicines. As you know, there is always a cost-benefit analysis to be done for each medicine given the patient's overall situation.
There is the issue of acute vs. chronic rejection. As best as I can tell, most of the research involving cytokine activity and transplantation has been done in the context of acute rejection in animal models. As you know, acute and chronic rejection are very different immunologically speaking. Because there are so many nonimmunological factors involved in late-stage loss of kidney transplant function, the term chronic allograft nephropathy is now in vogue to replace rejection, which is immunologically based. Acute rejection is characterized by a relatively narrow range of direct immunological pathways (including prevalence of cytokine activity), while chronic "rejection" involves a much broader range of factors, embracing indirect immunological and nonimmunological causation. The relevant point here is that herbs which stimulate Il-2 production (for instance) are probably more potentially dangerous during year 1 posttransplant than in years 5 or 10.
I don't think there is a scientific basis for saying, "patients having transplants must not be given herbal therapies," as Dr. Collin has done. As for your warning that "all herbal medications should be presumed unsafe for transplants until proved otherwise," I think that this amount of caution, though well intentioned, is too broad and too extreme. If we wait for this iron-clad proof to appear, we shall be waiting a very long time. Who is going to do the expensive clinical research with transplant patients? Certainly not herbal medicine manufacturers. In the meanwhile, the known benefits of those herbs would not be available to transplant recipients, and they will be subjected to the side effects of pharmaceuticals used in their place. Benefits include preserving graft function by safely ameliorating the harmful effects of comorbidities such as diabetes and hypertension. Well-trained NDs and holistic MDs should be able to weigh the risks and benefits of each medicine used given the health challenges of their patient by using regular lab testing for relevant markers. In the case of transplant recipients, the cost of abiding by a generic prohibition or discouragement for all herbal therapies discounts their potential for benefit.
Dr. Steven Hecht
1. Spelman K, Burns JJ, Nichols D, Winters N, Ottersberg S, Tenborg M. Modulation of cytokine expression by traditional medicines: a review of herbal immunomodulators. Alt Med Rev. 2006;11(2):141.
Dr. Henderson Responds
I would definitely agree that natural medicine has much to offer transplant recipients. The side effects of antirejection drugs are very hard to live with. Most people perceive this as a happy ending and don't think about the consequences of turning down the immune system.
In writing my doctoral thesis, I looked at about 50 herbs and very few of them were favorable. There are many good studies looking at specific herbs and transplantation with both animal models and humans, which can help guide naturopathic doctors into making safe choices.
One study in a murine model showed that transplanted kidneys lasted 30% longer with green tea in addition to transplant medications than transplant medications alone.1 Green tea is directly antibacterial, antifungal, and antiviral, which is important for an immune suppressed patient. Green tea also helps prevent skin cancer, which is the #1 cancer in the transplant population. Unfortunately, many transplant patients are needlessly cautioned against the use of green tea.
Some people disqualify herbs because they lower levels of the transplant medications, but I don't think that it's necessarily the case. Green tea lowered the calcineurin inhibitors, but in spite of that, the in vivo model showed that it increased graft survival. As long as the patient keeps to a consistent routine, it's easy to adjust the transplant medications as they're measured with each visit to the transplant doctor. For this reason, I'm not against pomegranate, as long as the patient begins it slowly and stays consistent.
It can be hard to quantify immune-modulating herbs and that can make it difficult to determine the safety with transplantation. It may raise Il-2 and lower another cytokine. However, Il-2 is only one aspect of immunity; but as all transplant medications work by lowering Il-2, it is by far the most important parameter. Ginseng raised the leukocyte count but they were less reactive. That may be part of its action as an adaptogen, which brings immunity up when you need to be up and down when you need to be down. But its adaptive qualities are not tailored to the needs of a transplant patient. I still wouldn't use it with a transplant, as you're asking the body to do something against its natural inclination.
Some of the herbs that my colleagues use concern me quite a bit. I can't stress enough that transplantation is a branch of medicine that is not welcoming to an integrative approach. My personal experience as a patient was that when anything went wrong with my transplant, my transplant doctors, knowing what I do for a living, were always quick to say, "It's an herb. Stop taking those herbs." Even when it was very clearly the medications at fault, the herbs were always perceived to be at fault. My transplant was only expected to last a few months due to recurrent FSGS, but using herbs and other supplements, I kept it going for 6 years. You'd think that they'd be curious as to what I was doing and why I wasn't following the typical course, but they weren't.
I play it very defensive with transplant patients and always give citations to studies in case they want to present them to their transplant doctors. I'm always ready for an angry transplant nephrologist to come knocking on my door. (And this does happen!) Often when a transplant fails, someone is made to take the blame and naturopathic doctors should be aware of this. Even the best patient rapport can turn sour when family, friends, and the transplant surgeon are against the use of naturopathic medicine.
Among the herbs that were proved safe for transplants, I found help for GI distress, infection, blood sugar regulation, bone density, and cancer prevention. There really is a lot that we can do with what has been tested so far. I also found coenzyme Q10 and L-carnitine very helpful to kidney transplant patients. It's not that naturopaths can't treat transplant patients, but we should use empirical research and not rely on data for the general population.
Dr. Jenna C. Henderson
1. Bayer J, Gomer A, Yilmaz D, Amano H, Kish D, Fairchild R, et al. Effects of green tea polyphenols on murine transplant-reactive T cell immunity. Clin Immunol. 2004 Jan;110(1):100–108.