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THe paTH aHeaD
First Do No Harm
Joseph Pizzorno, ND, Editor in Chief
am very sure that clinicians reading this journal believe, as I do, that priority number one when dealing with patients is “do no harm.” In our work to help heal our patients, we are all very conscious of this wise adage from Hippocrates (although he did not exactly state it this way, his many writings are quite clear about intent). Many patients are harmed by conventional medicine, so it’s easy to throw rocks. I found quite interesting a recent study that found that while 10% of the healthcare dollar is spent on drugs, a remarkable 13% is spent on treating the adverse effects of drugs.1 In other words, we spend more on treating the damage done to patients by drugs than on the drugs themselves. Not all of this expense is surprising, since some seriously ill patients are being treated. Nonetheless, it is a huge burden on patients and the healthcare system and so much of it is unnecessary. Unfortunately, that does not mean that our therapies, no matter how natural, are not without risk of harm themselves. Yes, the medicines we use have a very good therapeutic index (the ratio between the toxic dose and the therapeutic dose), which makes them safer to use. However, adverse reactions do happen, such as direct toxicity at high dosages (eg, the vitamin-D poisoning that happened in Boston when a dairy apparently made mistakes with fortification),2 normally safe dosages toxic to those with specific susceptibility or disease (eg, 10 000 IU vitamin D in those with granulomatous disease3), or interaction with drugs that makes them more or less toxic by increasing or decreasing (eg, St John’s wort increasing the rate of clearance of cyclosporine4) drug metabolism and accentuating or inhibiting activity (eg, curcumin decreasing chemotherapy-induced apoptosis of cyclophosphamide5). So how do we minimize the risk of harming our patients? By being very knowledgeable about the dosage limits and early symptoms of toxicity. Following is a modified version of the table I created for a chapter I wrote for the upcoming 4th edition of the Textbook of Natural Medicine.6 It represents my current best understanding of the maximum safe dosages of supplemental nutrients and the possible toxicity symptoms to watch for. Note that I have added comments where I think there are additional factors to consider. The potential for toxicity is well documented in the research literature. But how often does an adverse drug reaction occur with a vitamin supplement and how serious is the event? It’s difficult to determine. The best data I could find is from the American Association of Poison Control Centers.7 (The data are quite complex, so I hope I have interpreted it accurately.) In 2009, there were 2 479 355 calls to poison-control centers for possible substance reactions. Of these, 72 768 were for “vitamins.” There were no deaths, but 17 incidents were considered major. There were 29 417 calls about ingestion of “dietary supplements/herbals/homeopathics.” One death and 24 major reactions were reported in the
category of “unknown dietary supplement.” For “electrolytes and minerals,” the number of calls was 34 083 with 2 deaths (one each sodium and iron) and 18 major events. The vast majority of calls, about 75%, for were children up to 5 years of age; therefore, most of the toxicity most likely occurred in children accessing these substances. Of the 1 564 773 calls for pharmaceutical ingestion, 497 ended in death and 7395 were considered major reactions. I suspect this underreports that actual incidence of reactions to dietary supplements but should be within the ballpark. Bottom line: Vitamin toxicity does not appear common. Rather, it appears that children having unintended access to supplements is the real danger. Nonetheless, the risk of adverse reactions is not zero and much more likely to occur at high dosages. In This Issue My friends Robert A. Ronzio, PhD, and Patricia A. Ronzio, MEd, provide us with an integrated model for understanding and addressing the stress factors that inhibit behavioral change. I really like their approach as they take us beyond the typical—and sadly limited—efficacy of traditional patient-education programs to the much more effective “insightful learning.” John Neustadt, ND, and Steve Pieczenik, MD, PhD, are frequent and welcome contributors to IMCJ, as their articles are always directly clinically relevant. In this issue, they discuss the use of vitamin K2 in the prevention and treatment of osteoporosis as well as bisphosphonate-related osteonecrosis of the jaw. While they prefer the MK4 form of vitamin K2, I think MK7 (as well as other long-chain vitamin K2) may be of equal importance due its much longer half-life in the body. Nonetheless, they make a very compelling case that MK4 is an extremely important nutrient for these serious conditions. A trend that I hope will continue is the increasing number of case histories and pilot studies we are receiving as article submissions. Renee P. Meyer, MD, and Terrence X. O’Brien, MD, MS, present us with a study detailing the use of an herbal/homeopathic medicine in the treatment of Veterans Administration patients with congestive heart failure. Good to see that our medicine is being adopted for an increasingly diverse range of patients. I am very excited to see John Weeks’s commentary that Washington state is now promoting midwifery as a safe, cost-effective alternative to expensive hospital births. My, how the times have changed! In the late 1970s, I had the privilege of providing women with the option of home births. I very much enjoyed welcoming new lives into the world surrounded by their families, and to this day, I still miss those special times (on the other hand, I certainly do not miss the middle-of-the-night calls). The cost-effectiveness of home births was powerfully brought to my attention by a patient whose first child I delivered. She had reluctantly opted for birth
Integrative Medicine • Vol. 11, No. 2 • Apr/May 2012
Pizzorno—The Path Ahead
Small GW.62(13):3868-3675. potentiation of anticoagulants. No. drowsiness. 1992. Phylloquinone (K1). even at large doses (250 mg/d). unlike menadione (K3). cramps. nausea. long bone growth retardation Anorexia. 2011 Jan 13. Caution with anticoagulant medications. But one disagreement Bill. nausea. flatulence Increased urinary oxalate and uric acid levels in rare cases No reported side effects from oral administration at therapeutic doses Abdominal distension. sleep disturbances. Jacob CH. vomiting Possible hepatotoxicity Sensory and motor neuropathy. blurred vision. To share or copy this article. Editor in Chief drpizzorno@innovisionhm. vomiting Premature epiphyseal bone closing.11:9. Dietary curcumin inhibits chemotherapy-induced apoptosis in models of human breast cancer. Judson MA. In press. Toxic Dosages. Green JL. 2010. is not associated with side effects when given orally. eg. by an obstetrician once her husband had a job with health insurance. headache. but very high dosages. He SM. BMC Health Serv Res. 2002. Edmund NA. natural childbirth at home does not just decrease healthcare costs. Health care use and costs of adverse drug events emerging from outpatient treatment in Germany: a modeling approach. 2001. Moore DT. Teirstein AS. Cao C. Joseph Pizzorno. hyperirritability. 3. fatigue. GA: Elsevier. Zhou SF. which may be due to contaminants introduced during synthesis. anemia Teratogenesis. Baughman RP. Shi YY. severe hepatic damage and enlargement. May pose increased cancer risk. To subscribe. Bill Benda. Shao Q. polydipsia Hypercalcemia: risk of soft tissue calcification at lower dosages in those deficient in vitamin K. loss of hair. synthetic form is a risk for heavy smokers or asbestos-exposed patients not taking other antioxidants Anorexia. Curr Drug Metab. [Epub ahead of print] 5. Clin Toxicol (Phila). et al. That was until the couple found out that the birth-coverage deductible was higher than my fee! For healthy. low-risk women. 11. Contraindicated in granulomatous disease. 2. 5g/d may lead to cobalt poisoning. Very interesting to see naturopathic and conventional medical students talking together. vomiting. I suspect this ADR is due to concurrent vitamin D deficiency.com http://twitter. Sneed KB. muscular stiffness and pain. polyuria.326(18):1173-1177. Cancer Res. Leidl R.com Table. Hypervitaminosis D associated with drinking milk. No toxic effects have been reported for oral administration No toxic effects have been reported for oral administration No toxic effects have been reported for oral administration. Infants: 75-300 000 IU Adults: 2-5 million IU Infants: 18 000-60 000 IU/d Adults: 100 000 IU/d Pregnant women: 10 000 IU/d Vitamin D Short-term: Long-term: Vitamin E 1000-3000 IU/kg >40 000 IU/d Long-term: 1200 IU/d Vitamin K Water-soluble Vitamins Ascorbic acid Short-term: Long-term: Biotin Folic acid Niacin Niacinamide Pyridoxine Riboflavin Thiamin Vitamin B12 Long-term: none >10 g/d >3 g/d Long-term: >10 mg/d Long-term: 15 mg/d Short-term: 100 mg/d Long-term: 2000 mg/d Long-term: 300 mg/d Long-term Long-term Long-term Nausea. Cantilena LR Jr. Rumack BH. bleeding lips. Holick MF. Giffin SL. 2009 Annual Report of the American Association of Poison Control Centers’ National Poison Data System (NPDS): 27th Annual Report. exacerbation of hypertension. as near as I can tell. visit imjournal. Murray M. 6. ND.com. nausea. In: Pizzorno J. 2012 Jan 18. Bronstein AC. 4th ed. Transient flushing. bulging fontanels. diarrhea..com/drpizzorno Pizzorno—The Path Ahead Integrative Medicine • Vol. Chen XW. Orlowski RZ. cracking and peeling skin. Clinical characteristics of patients in a case control study of sarcoidosis. 7. Stark RG.48(10):979-1178. John J. diarrhea. it is a special bonding experience for the whole family. Am J Respir Crit Care Med. eds. Textbook of Natural Medicine. finishes this issue with his usual provocative insights. headache. Vitamin toxicities and therapeutic Monitoring. vomiting Headache. 2 • Apr/May 2012 11 . anorexia. Pizzorno J. 4. Severe weakness.164(10 Pt 1):18851889. headache. Use ISSN#1543953X. Spyker DA.This article is protected by copyright. and Symptoms of Commonly Prescribed Vitamins Vitamin Fat-soluble Vitamins Carotene Vitamin A Short-term Long-term Toxic dosage Long-term: none Toxic Signs and Symptoms (Comments) No apparent toxicity. please visit copyright. indeed. Atlanta. MD. you are consistently demonstrating that you do. N Engl J Med. Somasundaram S. Anorexia. still have the time and energy to change the world! REFERENCES 1. nausea. Herb-drug interactions and mechanistic and clinical considerations. Alpha-tocopherol used alone may increase cardiovascular disease risk due to competition with gamma form. Signs.
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