Back to Bloodletting?

Review of: Facchini, FS. The Iron Factor of Aging. Why Do Americans Age Faster? : Fenestra Books, 2002, pp 180. This book is a bold and imaginative discussion of the pathophysiology of aging, cancer, vascular disease, and diabetes mellitus (DM). It is fun to read, but its conclusions and recommendations will not make it into a compendium of evidence-based medicine. The author argues that free radicals are the root of all evil: that they oxidize proteins and promote protein glycosylation leading to the changes associated with aging, that they damage nucleic acids promoting cancer, and that they oxidize lipids promoting vascular disease. But free radicals are generated in vivo by the intermediary metabolism that maintains life. So what to do? Iron promotes the formation of free radicals (certainly in vitro, but not so certainly in vivo, where iron is bound to proteins like ferritin that limit its participation in free radical generation). The author argues that if in vivo iron stores were diminished, there would be less free radical formation and less cancer, vascular disease, and DM (the latter also linked to free radical generation and iron excess in the author’s exposition) and slower aging. The author’s principal remedy is to inhibit iron absorption with a diet that has iron-poor constituents and large amounts of phytates and tannins (both of which inhibit iron absorption; the latter, based on in-vitro studies, also inhibits glucose and galactose absorption). In the author’s own words, ‘‘a diet with a high tannin content and with low iron availability should be recommended forymales after 30 years of ageyfemales after 40.yThe main objectiveyis to increase the meal-time intake of tannins and calcium with the aim of lowering iron bioavailability and glycemic index of foods.yCardinal feature is to have a daily intake of 2 to 10 species of raw vegetables.yFresh fruit is not recommended.yJuices should be substituted byywine, tea, soy, sugar-free cocoa-based drinks, and other high tannin containing products.yBeverages high in tanninsyshould only be consumed throughout the meal. ’’ (If the author had his choice there would be more uncooked vegetable consumption, but this is as much as he thinks a middle-aged gastrointestinal tract could stand) The author’s arguments in support of this recommendation begin with the speculation that about 1 million years ago, our ancestors first discovered fire and began cooking. Before that, life was supported by a diet with limited iron availability; cooking diminishes the phytate content of food (phytates limit the absorption of the iron in food). Thus man graduated over the course of millennia from a healthier iron-poor state to a less-healthy iron-plenty state. The author further argues that the societies with least age-related disease are the Japanese (diet: low fat, high carbohydrate), the French (diet: red wine and creamy foods), and those bordering the Mediterranean (diet: cheese and olive oil). The common thread in each of these largely divergent dietary patterns is high intake of tannins and low dietary iron bioavailability. The author has the courage of his convictions. He has been a one-man army waging war on iron. In recent publications, he has demonstrated that ‘‘near iron deficiency’’ induced by phlebotomy puts gout into remission and decreases cardiac risk factors. He has also found that a diet with low iron bioavailability and high tannin contentFincluding abundant tea, red wine, white meat, and extra virgin olive oilFslows the progression of diabetic nephropathy (angiotensin-converting enzyme inhibitors given to control and experimental groups). This published experimental work is, to this reviewer, amazing, but the gout and vascular disease risk factor studies were not controlled, and the DM study was not blinded and awaits confirmation by other investigators. Problems arise because some of the supporting argument is uncritical. The author argues that DM may be secondary to oxidative damage promoted by iron because higher serum ferritins are associated with an increased frequency of DM. He does not point out, as the authors of the cited papers do, that serum ferritin is an acute phase reactant and the linkage between DM and higher serum ferritin may derive from a common etiology: inflammation. The author cites data showing positive health-related consequences from living on mountains; the incidence of DM and hypertension decreases with increasing altitude. From this the author argues that hypoxia is the commonality and that oxygen damage promoted by iron is inhibited by reducing the amount of oxygen in the environment. Can hypoxia be good for you? Some current beliefs would have seemed strange a generation ago. Nowadays starvation is thought Address correspondence to: Simeon Pollack, MD, Department of Medicine, Albert Einstein College of Medicine, 1300 Morris Park Ave. Bronx, NY 10461. E-mail: thepollackfam@earthlink.net From the Department of Medicine, Albert Einstein College of Medicine, Bronx, New York.