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Begin at the Beginning
Arch Fam Med. 2000;9:39.
The journey that led to the article, "Effect of Calcium Supplementation on Serum Cholesterol and Blood Pressure" in this issue of the ARCHIVES1 began with my lifelong interest in the origins and evolution of humans. This interest was maintained and strengthened during my 9 years of private practice in family medicine, seeing persons suffering with and dying of chronic diseases that seemed to be preventable. I wondered, what is it that we eat, do, etc, that is discordant with our evolutionary heritage that is causing these chronic diseases that appear to be diseases of modern civilization?
In 1985 an article2 appeared in the New England Journal of Medicine that proved to be the precipitating factor for a major change in my career and life. The article, "Paleolithic Nutrition," was an exciting work that provided estimates of the nutritional composition of the Paleolithic diet, the diet of our genus Homo from the transition of Homo erectus to Homo sapiens, through the refinement of archaic Homo sapiens to Homo sapiens sapiens, to the agricultural revolution. Estimates of differences in the nutritional composition between Paleolithic diets and those of modern Americans were remarkable. Many were already well known, such as the consumption of animal fat, which is known to be associated with serum cholesterol levels and ischemic heart disease. But other, less well-known differences struck my eye. The consumption of calcium by our Paleolithic ancestors was estimated to be 1500 to 2000 mg/d compared with our modern average intake of 740 mg/d. What implications might such a difference have for modern diseases? Osteoporosis seemed a logical, but not original hypothesis. But might there be other health consequences?
The same week that I read "Paleolithic Nutrition," I read a review of calcium supplements in a now forgotten source. A bit of information in the review caught my eye: on average, only about 30% of ingested calcium is absorbed, the rest is excreted in the feces. With the information from the article on Paleolithic nutrition still on my mind, I reasoned that humans apparently evolved under conditions of high free calcium levels in the gut. I wondered: could our current lifelong conditions of low gut calcium permit mechanisms leading to colon cancer, a disease of modern civilization? (I know my article is about heart disease, not colon cancer, but bear with me a while longer.)
To make a long story short, I uprooted my family and moved from Beaufort, SC, to Minneapolis, Minn, to begin a fellowship at the University of Minnesota with the aim of pursuing my question. My literature review revealed that if we eat an amount of calcium in excess of absorptive needs and what it takes to bind free phosphate in the gut, there will be free calcium in the gut that will bind bile acids (which are the result of fat intake), sparing the colon epithelium from their damaging effects.3 The intake of calcium required to bind the average amount of bile acids in the colon of the average American: 1500 to 2000 mg/d! Furthermore, the equivalent of such amounts reduced epithelial cell damage and tumorigenesis in the colons of rodents.
To make another long story short, I subsequently conducted analyses, wrote grant applications, and conducted studies to investigate calcium as a possible protective agent against colon cancer. My work included a prospective cohort study analysis of calcium and incidence of colon cancer4; a case-control study of calcium and colon adenoma5; a pilot randomized, controlled clinical trial of calcium and colorectal epithelial cell proliferation (a putative early marker of risk for colon cancer)6; then the follow-up full-scale trial of calcium and colorectal epithelial cell proliferation7 that provided the vehicle for the article in this issue of the ARCHIVES.1 Happily, these investigations and those of others provided support for my hypothesis.
In conducting these investigations, I kept recalling: binding of bile acids, that's what cholestyramine and colestipol do to lower cholesterol and reduce risk of ischemic heart disease. I wondered: can calcium intake at 1500 to 2000 mg/d lower cholesterol levels and reduce the risk of ischemic heart disease? A literature review revealed that the equivalent of these doses does do these things in laboratory animals (it also affects blood pressure). This led me to a prospective cohort study analysis of calcium and ischemic heart disease mortality in women (higher calcium intake was associated with reduced risk),8 and a grant application to study cholesterol and blood pressure along with colorectal epithelial cell proliferation in the full-scale randomized, controlled clinical trial noted above. The results of this investigation are presented in this issue.1
In the beginning I did not anticipate the journey that I have taken. Eleven years ago I was a family physician in full-time private practice who liked to read about human origins. Today, I am, to my knowledge, the first family physician associate director for a cancer center. I continue to reflect on the beginnings of our species and the problems I encounter in my panel of patients at the University of South Carolina. I have enjoyed my journey, and look forward to its continuance.
My advice to an aspiring new researcher: as the good witch of the North told Dorothy on how to get to Oz, "just begin at the beginning," then, "just follow the yellow brick road." Enjoy your journey!
Roberd ("Robin") M. Bostick, MD, MPH
Columbia, SC
REFERENCES
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1. Bostick RM, Fosdick L, Grandits GA, Grambsch P, Gross M, Louis TA. Effect of calcium supplementation on serum cholesterol and blood pressure: a randomized, double-blind, placebo-controlled clinical trial. Arch Fam Med. 2000;9:31-39.
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2. Eaton SB, Konner M. Paleolithic nutrition: a consideration of its nature and current implications. N Engl J Med. 1985;312:283-289.
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3. Bostick RM. Human studies of calcium supplementation and colorectal epithelial cell proliferation. Cancer Epidemiol Biomarkers Prev. 1997;6:971-980.
ABSTRACT
4. Bostick RM, Potter JD, Sellers TA, McKenzie DR, Kushi LH, Folsom AR. Relation of calcium, vitamin D, and dairy food intake to incidence of colon cancer among older women: The Iowa Women's Health Study. Am J Epidemiol. 1993;137:1302-17.
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5. Bostick RM, Potter JD, Grandits GA, et al. Calcium and vitamin D intakes and risk for adenomatous polyps [abstract]. Proc Am Assoc Cancer Res. 1997;38:109.
6. Bostick RM, Potter JD, Fosdick L, et al. Calcium and colorectal epithelial cell proliferation: a preliminary randomized, double-blinded, placebo-controlled clinical trial. J Natl Cancer Inst. 1993;85:132-141.
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7. Bostick RM, Fosdick L, Wood JR, et al. Calcium and colorectal epithelial cell proliferation in sporadic adenoma patients. J Natl Cancer Inst. 1995;87:1307-1315.
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8. Bostick RM, Kushi LH, Wu Y, Meyer K, Sellers TA, Folsom AR. Relation of calcium, vitamin D, and dairy food intake to ischemic heart disease mortality among postmenopausal women. Am J Epidemiol. 1999;149:151-161.
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RELATED ARTICLE
Effect of Calcium Supplementation on Serum Cholesterol and Blood Pressure: A Randomized, Double-blind, Placebo-Controlled, Clinical Trial
Roberd M. Bostick, Lisa Fosdick, Greg A. Grandits, Patricia Grambsch, Myron Gross, and Thomas A. Louis
Arch Fam Med. 2000;9(1):31-38.
ABSTRACT
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