‘Focal Segmental Glomerulosclerosis: A Naturopathic Perspective’

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 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.

Notes

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.