Physician skepticism common as patients increasingly turn to nutrient- or botanical-based remedies
When Florida physician Bernd Wollschlaeger, MD, asked an elderly female CKD patient to tell him all the medications she was taking, she listed four or five. When he asked her to bring her medications to her next visit, however, she brought in a shoebox filled with 84 different supplements. He asked her why she had not mentioned these at the previous visit, and she responded, “Well, these aren't medications; they're supplements, so I didn't think they mattered.” As Dr. Wollschlaeger relates, she did not realize that using just one of these compounds could potentially interact with her prescription medications or otherwise cause a health setback.
As chairman of both the medical advisory board and the CME committee of the American Nutraceutical Association and coauthor of the American Botanical Council's The ABC Clinical Guide to Herbs, Dr. Wollschlaeger knows just how common the use of vitamins, supplements, herbs, botanicals (plants or plant-derived substances), functional foods (such as tomatoes, for their lycopene content), and medicinal foods (such as health bars with added medication) has become.
“This is happening a lot in patients with chronic kidney disease, diabetes, hypertension—chronic diseases that affect the kidney,” says Dr. Wollschlaeger, clinical assistant professor of family medicine at the University of Miami and owner of Aventura Family Health Center in North Miami Beach, Fla.
Estimates put the U.S. dietary supplements industry at $23 billion in sales. This is largely driven by the ever-expanding population of chronically ill individuals who are self-prescribing their way to potentially greater energy, regained muscle, and relief from the side effects of the multiple medications in the regimen they take every day.
Patients searching for options
“It's important to understand that the desire to seek out alternatives for feeling better is initiated from the patient side,” affirms Cathy M. Goeddeke-Merickel, MS, RD, LD, managing editor of the Renal Nutrition Forum of the Renal Dietitians Dietetic Practice Group. “The chronically ill population is looking for options to feel better or lessen the side effects of the long list of prescribed medications.”
By Goeddeke-Merickel's estimates, awareness and acknowledgment of nutraceutical and botanical use has soared over the years, especially in the past five years, a trend that has been addressed by the National Kidney Foundation (NKF) and the American Dietetic Association (ADA). For example, “the NKF has recognized the increased utilization of these products in its patient population and is providing more patient-education materials. This area is a significant topic of interest at the national NKF meetings.”
Meanwhile, nutraceuticals meet with widespread skepticism among physicians, who believe, perhaps, that the use of nutrient-based supplements is not supported by strong evidence. This skepticism is not new. Consider this comment on medicinal foods that appeared in The Journal of the American Medical Association 101 years ago:
The facts in regard to so-called medicinal foods—their failure to measure up fully to what has been and is claimed for them, their great relative cost, their dangerous alcohol content, and the likelihood that some physician following blindly the optimistic suggestions of those commercially interested will do his patients harm—these facts are now public, and every intelligent physician who becomes familiar with these facts may be counted on to take the necessary steps to guard himself and his patients against placing more confidence in these articles than they deserve (JAMA. 1907;48:1681).
The seeds of doubt may be planted as early as medical school, where the topic of nutraceuticals rarely is on the curriculum. Some practitioners are put off simply by the unfamiliar term, which was coined in 1989 by Stephen L. DeFelice, MD, founder of the nonprofit Foundation for Innovation in Medicine (www.fimdefelice.org) in Cranford, N.J. He shared his definition with Renal & Urology News: “A nutraceutical is a food or part of a food that has a medical or health benefit, including the prevention and treatment of disease. It can be a whole natural food, a processed food, a pill, or a liquid.”
Other experts and organizations have put their own spin on what the field of nutraceuticals encompasses, but generally speaking, a nutraceutical is a bioactive chemical or compound with medicinal or health benefits that is isolated from a food source and concentrated in a supplement form, to be used at higher concentrations than could be obtained solely from dietary sources.
Do they work?
For many clinicians, the biggest problem lies in whether the scientific evidence supports the use of these compounds in CKD. “The question of when nutrients or even drugs are beneficial is very difficult to answer,” notes Joel Kopple, MD, professor of medicine and public health at the David Geffen School of Medicine at the University of California in Los Angeles. As a nephrologist with a long-standing interest in nutrition, Dr. Kopple has published hundreds of papers addressing nutrition in renal disease and has served as president of the American Society for Parenteral and Enteral Nutrition and Metabolism as well as the International Society for Renal Nutrition.
“Nephrologists as a group tend to be rather skeptical of therapeutic nutritional management,” he said, “but since the 1990s it has become very apparent that protein-wasting malnutrition is associated with very poor outcomes, increased morbidity, increased mortality, and decreased quality of life.”
One obstacle to nutraceutical acceptance is the gray area between a nutrient and a real drug, but some nutraceuticals are available only by prescription. Coenzyme Q10, which can be deficient in people with diabetes, is a registered pharmaceutical in some countries outside the United States.
Another ingredient straddling the nutrient/pharmaceutical line is calcitriol, which is commonly prescribed to prevent or treat low calcium levels, hyperparathyroidism, and bone disease in people with impaired kidney function. Calcitriol is the most active naturally occurring form of vitamin D, but the FDA defines it as a drug.
Dr. Kopple agrees with imposing careful regulation on a substance that can so easily be ingested at toxic levels. In fact, he would not classify calcitriol as a nutraceutical because it has been chemically modified, but he points out that calcitriol “is simply a compound that has been only slightly modified from what you eat in food. The difference between 1,25-dihydroxycholecalciferol (calcitriol) and the vitamin D you'll eat or make from sunlight is just two hydroxyl groups added at different parts of the compound.
“When it comes to compounds like vitamin D or some of the newer modifications that I use in kidney disease,” he adds, “I don't think there's a nephrologist alive who wouldn't agree that these can be very, very valuable agents for people to take.”
Unrealistic expectations
Conclusive evidence supporting or rejecting the usefulness of any given nutraceutical is hard to come by. For example, although vitamin E, an antioxidant, has been shown to reduce endothelial dysfunction in CKD patients, it also has been implicated in increasing all-cause mortality.
“The studies and evidence are always evolving,” says Rebecca Wright, editor of Nutraceuticals World, an industry magazine. “Some of these ingredients have been around for 5,000 years. Not everything can be considered in terms of double-blind, placebo-controlled trials—especially in the case of these products.”
The research knife can cut two ways, making someone less of a believer rather than a stronger one. At one time, Dr. Kopple advocated use of the amino acid-derived l-carnitine, which had received a lot of scientific support as a useful nutraceutical in CKD. He has published several papers on the nutrient, reporting on his own short-term trials that have often yielded benefits. Long-term clinical trials of carnitine treatment in renal failure patients, however, have produced ambiguous results at best. “There has never been a reproducible clear benefit with carnitine as there is with, say, furosemide.”
Those rare individuals with genetic defects involving the carnitine-synthesis apparatus become severely deficient in carnitine—a lethal situation. Carnitine can be a lifesaving substance for them. “So for these rare cases, carnitine could be considered a quintessential nutraceutical,” Dr. Kopple said.
As a clinical consultant and nephrology dietitian for both pre-dialysis and hemodialysis patients, Goeddeke-Merickel has seen patients respond favorably to carnitine and cites clinical studies in which dialysis patients have reported improved quality of life during l-carnitine administration.
Negativity not helpful
CKD patients, in particular, are prone to use nutritional supplements and any other OTC product that promises to help them rebuild muscle and feel more energetic. Therefore, it is imperative for physicians to screen patients for such usage and try to do so with an open mind.
A dismissive attitude from the doctor will not discourage patients from using these products; it may only prompt them to be more secretive about doing so. During hospital admissions for CKD patients, surgeons sometimes see increased bleeding times. Only later do they find out that this may be linked with a nutraceutical or botanical the patient has taken but has not acknowledged to the doctor beforehand, Goeddeke-Merickel says.
Dangerous mixtures possible
The patient may be consuming supplements that contain a dangerous mixture of products. A Chinese herb mixture, for example, can include licorice powder, black pearl, or artemisia (wormwood), all of which can be nephrotoxic. Single-ingredient herbal extracts may be a safer choice, but any ingredient must be reviewed by a doctor, pharmacist, or dietitian, Goeddeke-Merickel says.
To decrease sodium levels, CKD patients may think they should ingest agents with diuretic properties, such as juniper, celery seed, or horsetail. These can be toxic to the kidneys and otherwise harmful.
Furthermore, CKD patients often have other maladies that they may try to relieve with nutraceuticals, such as glucosamine and chondroitin for osteoarthritis. “Just be-cause a nutraceutical isn't specific to CKD doesn't mean that CKD patients aren't using it,” Goeddeke-Merickel cautions.
For example, she often is asked about the safety of fish-oil supplements. Although their cardiovascular benefits have been legitimized by research, these products can potentiate dangerous bleeding problems in CKD patients.
A Physician Who Founded a Nutraceutical Company
PHYSICIANS WHO question the credibility of nutraceutical manufacturers might have their doubts quelled by Seth J. Baum, MD, a cardiologist in Boca Raton, Fla. He also is the head and founder of Vital Remedy MD (www.vitalremedymd.com), a maker of renal and cardiovascular vitamins and supplements since 2002.
“I'm on both sides of the fence here because I've got one foot on the industry side and one foot heavily steeped in the conservative medicine side,” Dr. Baum said.
Dr. Baum, who formulates all of his company's products himself, said he understands why his medical colleagues might be worried about products marketed by some of his industry associates. “Unfortunately, you have a lot of charlatans out there who are promoting products that have no evidence behind them,” he says. “But then there is a large segment that does have evidence [of nutraceutical efficacy], perhaps just not the standard that we'd like to see in the world of evidence-based medicine, because of the expense of doing trials.”
Doctors who flatly dismiss nutraceuticals should “have the confidence as physicians to try something and not be terrified that they'll hurt a patient with a nutraceutical, unless there's some real evidence of risk. We need to return to the foundation of medicine as art for physicians. We need to read as much as possible, learn as much as possible, and then put the picture together as best as we can and make recommendations based upon our knowledge and our experience.”
l-Carnitine May Reduce LVH in Dialysis Patients, Study Finds
l-CARNITINE supplementation decreases left ventricular mass in hemodialysis patients, according to investigators at the Kidney Center of Shinrakuen Hospital in Niigata, Japan.
In a study, 10 patients received 10 mg/kg of oral l-carnitine three times per week over 12 months immediately following their dialysis sessions. Tai Sakurabayashi, MD, and colleagues used echocardiography to measure left ventricular fractional shortening (LVFS) and left ventricular mass index (LVMI) before and after the study period.
l-Carnitine treatment increased serum free creatinine from 28.4 to 58.5 mmol/L in patients. LVFS remained unchanged among both the treated patients and a control group of 10 untreated patients, according to investigators. LVMI fell significantly in the treated group from 151.8 to 134.0 g/m2. No significant LVMI change was observed in the untreated group.
“Supplementation with l-carnitine induced regression of left ventricular hypertrophy in patients on hemodialysis, even for those with normal systolic function,” the researchers concluded in Circulation Journal (2008;72:926-931).
In addition, l-carnitine supplementation also was associated with a 31% reduction in erythropoietin requirements but did not change hematocrit or BP levels during the course of the study.