In the second Jurassic Park movie (1), rich industrialist John Hammond (Richard Attenborough) tells Ian Malcom (Jeff Goldblum), that he has learned his lesson – you cannot control Nature (played by CG dinosaurs) with electric fences and technology. However, in the next breath he reports that he has a second island populated by these amazingly intelligent, doorknob-turning dinosaurs, and he has hatched a brilliant plan to send people there. Anyone who has watched this scene knows what is eventually going to unfold, and in the back of your mind you think “No way would people make that kind of mistake in real life”.
Unfortunately, I have seen the same type of folly played-out, in medicine and nutrition, when observational data documents an association between a nutrition factor and some disease-state, followed immediately by the press and popular opinion implying that the nutritional factor is the cause/cure for the disease-state. In the 1980’s it was beta-carotene and cancer, in the 1990’s it was vitamin E and heart disease, and in the early 2000’s it was folic acid-homocysteine and cardiovascular disease. Unfortunately, randomized data demonstrated that supplemental beta-carotene and vitamin E were more often harmful than helpful, while lowering homocysteine did very little in most circumstances.
When the observational data about vitamin D and, well, everything (cancer, cardiovascular disease, diabetes, critical illness, etc,….) was published, I was astounded that so many professionals immediately started supplementing large numbers of patients with very large doses of vitamin D without a single randomized study investigating safety and effectiveness. Considering the long list of nutrients that had demonstrated harmful effects with large supplemental doses since 1985, in contrast to the observational data, jumping on the vitamin D bandwagon felt as short-sighted as adopting a pet velociraptor shortly after narrowly escaping from Jurassic Park. The recent disappointing evidence from randomized studies (2-5) of vitamin D is again reminding us that observational studies should never, ever be used to infer cause and effect, and that clinical decisions should be based on adequate randomized data.
In the nutrition support arena, there are multiple observational studies since the 1980’s documenting an association between patients with poor outcomes and decreased nutrition intake. Distressingly, this is often suggested to imply that the inadequate nutrition was the cause of the compromised patient outcome (6-7). In contrast, the available randomized data demonstrate that modest calorie deficits in the early part of an ICU admission do not seem to cause negative patient outcomes (8-9). Additionally, attempts to enforce full nutrition delivery in the early phase of critical illness appear to increase length of stay, and may even increase mortality (10-13). Regrettably, some papers and editorials have not only made the case for causality based on observational data, but have directly compared the observational data with randomized studies, which is in opposition to every medical professional’s training. I think it is important that we do not let our desire to help malnourished and critically ill people, coupled with market forces and the need to fund research, cause us to forget what we have repeatedly learned the hard way: that making clinical decisions based on observational data can hurt people. Yes, to avoiding massive nutrition deficits and malnutrition, but we need better data before forcing in full calories in the earliest stages of critical illness.
“Oh, yeah…. Oooh, ahhh, ..that’s how it always starts. Then later there’s running and um, screaming.”
– Ian Malcolm, The Lost World: Jurassic Park (1997)
“Some of the worst things imaginable have been done with the best intentions.”
– Dr. Alan Grant, Jurassic Park III (2001)
1. The Lost World: Jurassic Park (1997), Universal Pictures.
2. Hansen KE, Johnson RE, Chambers KR, et al. Treatment of Vitamin D Insufficiency in Postmenopausal Women: A Randomized Clinical Trial. JAMA Intern Med. 2015;175(10):1612-1621.
3. Baron JA, Barry EL, Mott LA, et al. A Trial of Calcium and Vitamin D for the Prevention of Colorectal Adenomas. N Engl J Med. 2015 Oct 15;373(16):1519-30.
4. Amrein K, Schnedl C, Holl A, et al. Effect of high-dose vitamin D3 on hospital length of stay in critically ill patients with vitamin D deficiency: the VITdAL-ICU randomized clinical trial. JAMA. 2014;312(15):1520-1530.
5. Bischoff-Ferrari HA, Dawson-Hughes B, Orav EJ, et al. Monthly High-Dose Vitamin D Treatment for the Prevention of Functional Decline: A Randomized Clinical Trial. JAMA Intern Med. 2016 Feb 1;176(2):175-183
6. Wischmeyer PE. Ensuring Optimal Survival and Post-ICU Quality of Life in High-Risk ICU Patients: Permissive Underfeeding Is Not Safe! Crit Care Med. 2015;43(8):1769-1772.
7. Yeh DD, et al. Adequate Nutrition May Get You Home: Effect of Caloric/Protein Deficits on the Discharge Destination of Critically Ill Surgical Patients. JPEN 2016;40(1):37-44
8. Arabi YM, Aldawood AS, Haddad SH, et al. Permissive Underfeeding or Standard Enteral Feeding in Critically Ill Adults. N Engl J Med. 2015;372(25):2398-2408.
9. The National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network. Initial Trophic vs. Full Enteral Feeding in Patients with Acute Lung Injury: The EDEN Randomized Trial. 2012;307(8):795-803.
10. Sheean PM, Peterson SJ, Zhao W, et al. Intensive medical nutrition therapy: methods to improve nutrition provision in the critical care setting. J Acad Nutr Diet. 2012;112(7):1073-1079.
11. Braunschweig CA, Sheean PM, Peterson SJ, et al. Intensive Nutrition in Acute Lung Injury: A Clinical Trial (INTACT). JPEN 2015;39(1):13-20.
12. Taylor B, Brody, Denmark R, et al. Improving Enteral Delivery Through the Adoption of the “Feed Early Enteral Diet Adequately for Maximum Effect (FEED ME)” Protocol in a Surgical Trauma ICU: A Quality Improvement Review. Nutr Clin Pract. 2014; 29(5):639-648.
13. Haskins IN, Baginsky M, Gamsky N, et al. A Volume-Based Enteral Nutrition Support Regimen Improves Caloric Delivery but May Not Affect Clinical Outcomes in Critically Ill Patients. JPEN 2015 Nov 12[epub ahead of print]