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Providing perspectives on recent research into vitamins and nutritionals


Why Conduct Nutrition RCTs without Nutrition Assessment?

By Michael McBurney

When conducting randomized controlled studies (RCTs), a BIG challenge is that study participants often conceal information. Participants will lie to get into clinical trials. People are known to conceal health problems, deny use of prescription medications, and exaggerate symptoms to qualify for a study. This is a problem.

Nutrition RCTs are particularly difficult because a true placebo treatment does not exist. Everybody eats. Everybody has some level of nutritional status ranging across the spectrum of deficient, insufficient, and adequate.

As an example, epidemiologic data that cereal fiber protects against colorectal cancer led to a RCT testing the effect of increasing wheat-bran fiber intake (13.5 vs 2 g daily) on recurrence of colorectal adenomas. A dietary supplement of wheat-bran fiber did not protect against recurrent colorectal adenomas. A similar null effect on polyp recurrence was observed in the Polyp Prevention Trial (PPT) with a high-fiber, high fruit-and-vegetable, low-fat diet. Clearly, the lack of a fiber-polyp relationship wasn’t confined to dietary supplementation. What could be the explanation?

In the PPT, baseline fiber intakes were 18g/1000 kcal, well above the average intake of 14.8g for males and females over 1y of age. The reality is that participants in these two fiber and colorectal cancer RCTs were not typical American adults; they were eating more fiber (average intake ~19-22g/d) than most American adults. The epidemiological evidence associating dietary fiber intake with cancer risk was based primarily on intakes ranging between 8 and 23g daily, not increasing intake from a baseline intake of 20g daily.

Increasing nutrient intake affects health when people are not adhering to nutrient recommendations to maintain nutritional status. Involving participants at the upper end of nutrient status distribution in RCTs constructed to test epidemiological evidence does not generate data relevant to the majority of the population, and certainly not for the less fortunate.

Without assessing nutritional status of participants, eg. biological measures of calcium and vitamin D status, it is impossible to understand nutrient-health relationships.

Main Citation

Baron JA, Barry EL, Mott LA, Rees JR, Sandler RS, Snover DC, Bostick RM, Ivanova A, Cole BF, Ahnen DJ, Beck GJ, Bresalier RS, Burke CA, Church TR, Cruz-Correa M, Figueiredo JC, Goodman M, Kim AS, Robertson DJ, Rothstein R, Shaukat A, Seabrook ME, Summers RW. A trial of calcium and vitamin D for the prevention of colorectal adenomas. 2015 NEJM doi: 10.1056/NEJM011500409

Other Citations

Devine EG, Waters ME, Putnam M, Surprise C, O’Malley K, Richambault C, Fishman RL, Knapp CM, Patterson EH, Sarid-Segal O, Colanari L, Cirualo DA. Concealment and fabrication by experienced research subjects. 2013 Clin Trials doi: 10.1177/1740774513492917

Alberts DS, Martinez ME, Roe DJ, Gullen-Rodriguez JM, Marshall JR, van Leeuwen B, Reid ME, Ritenbaugh C, Vargas PA, Bhattacharyya AB, Earnest DL, Parish D, Koonce K, Fales L, Sampliner RE, and the Phoenix Colon Cancer Prevention Physicians’ Network. Lack of effect of a high-fiber cereal supplement on the recurrence of colorectal adenomas 2000 NEJM doi: 10.1056/NEJN200004203421602

Lanza E, Schatzkin A, Daston C, Corle D, Freedman L, Ballard-Barbash R, Caan B, Lance P, Marshall J, Iber F, Shike M, Weissfield J, Slattery M, Paskett E, Mateski D, Albert P, and the PPT Study Group. 2001 Am J Clin Nutr 74(3):387-401

Jacobs ET, Lanza E, Alberts DS, Hsu C-H, Jiang R, Schatzkin A, Thompson PA, Martinez ME. Fiber, sex, and colorectal adenoma: results of a pooled analysis. 2006 Am J Clin Nutr 83(2):343-349

Park Y, Hunter DJ, Spiegelman D, Bergkvist L, Berrino F, van den Brandt P, Buring JE, Colditz GA, Freudenheim JL, Fuchs CS, Giovannucci E, Goldbohm A, Graham S, Harnack L, Hartman AM, Jacobs DR, Kato I, Krogh V, Leitzmann MF, McCullough ML, Miller AB, Pietinen P, Rohan TE, Schatzkin A, Willett WC, Wolk A, Zeleniuch-Jacquotte A, Zhang SM, Smith-Warner SA. Dietary fiber intake and risk of colorectal cancer: A pooled analysis of prospective cohort studies. 2005 JAMA doi: 10.1001/jama.294.22.2849