SMOFLipid and resolution of cholelithiasis: Chance, and chance alone

Abstract

In a recent issue of Clinical Nutrition, Diamanti et al. reported an observation of the resolution of cholelithiasis, as documented by ultrasound in one patient and a modest decrease in estimated gallstone size in another patient following the substitution of SMOFLipid™ for conventional lipid emulsion. 1 Diamanti A, Papa RE, Panetta F. Disappearance of the gallstones under SMOFlipid: true or coincidental association? Clin Nutr;152(13):150–1. Google Scholar They propose a mechanism wherein biliary cholesterol saturation is decreased in association with increased dietary N-3 unsaturated fatty acid intake, and on this basis suggest the use of SMOFLipid™ for the prevention of gallstones in essentially all patients that receive long-term PN since by definition, all those patients with short bowel syndrome and motility disorders that also involve the biliary tract are at risk for development of biliary stasis, followed by cholelithiasis. This hypothesis was expounded upon by Klek in an accompanying letter/editorial. 2 Klek S. Reply to the letter to editor: disappearance of the gallstones under SMOFlipid: true of coincidental association?. Clin Nutr. 2013; 13: 152 Abstract Full Text Full Text PDF Scopus (2) Google Scholar That may be all well and good for a free-living, nutritionally autonomous individual, but both authors fail to realize the metabolism of orally consumed nutrients may differ substantially from intravenously infused nutrients. More importantly however, is that there is seemingly little relevance for patients that receive PN. The reason is because gallstones in these patients are not predominately cholesterol. On the contrary, they are predominately pigmented stones. 3 O'Brien C.B. Berman J.M. Fleming C.R. et al. Total parenteral nutrition gallstones contain more calcium bilirubinate than sickle cell gallstones. Gastroenterology. 1986; 90: 1752 Google Scholar , 4 Muller E.L. Grace P.A. Pitt H.A. The effect of parenteral nutrition on biliary calcium and bilirubin. J Surg Res. 1986; 40: 55-62 Abstract Full Text PDF PubMed Scopus (40) Google Scholar Further evidence strongly suggests gallstones appear to follow biliary sludge formation, 5 Messing B. Bories C. Kunstlinger F. Bernier J.J. Does total parenteral nutrition induce gallbladder sludge formation and lithiasis?. Gastroenterology. 1983; 84: 1012-1019 PubMed Google Scholar , 6 Doty J.E. Pitt H.A. Porter-Fink V. DenBesten L. The effect of intravenous fat and total parenteral nutrition on biliary physiology. J Parenter Enteral Nutr. 1984; 8: 263-268 Crossref PubMed Scopus (48) Google Scholar , 7 Matos C. Avni E.F. Van Gansbeke D. Pardou A. Struyven J. Total parenteral nutrition (TPN) and gallbladder diseases in neonates. Sonographic assessment. J Ultrasound Med. 1987; 6: 243-248 PubMed Google Scholar which is largely a suspension of pigment precipitates in bile, and is at least in part calcium bilirubinate as noted by Allen et al. 8 Allen B. Bernhoft R. Blanckaert N. Svanvik J. Filly R. Gooding G. Way L. Sludge is calcium bilirubinate associated with bile stasis. Am J Surg. 1981; 141: 51-56 Abstract Full Text PDF PubMed Scopus (106) Google Scholar Furthermore, conventional lipid emulsions do not alter the lithogenic index of bile. 6 Doty J.E. Pitt H.A. Porter-Fink V. DenBesten L. The effect of intravenous fat and total parenteral nutrition on biliary physiology. J Parenter Enteral Nutr. 1984; 8: 263-268 Crossref PubMed Scopus (48) Google Scholar Therefore, the proposed mechanism to explain the observation of Dianabti is not plausible, and I suggest their single patient observation may be a chance phenomenon and nothing more. The decreased size of the stone in the second patient could easily be related to the orientation of the stone in reference to the ultrasound probe as it is a three-dimensional structure being viewed in a single dimension. In fact, the infusion of low amounts of conventional lipid emulsion such as Intralipid™ may actually be a risk factor for development of PN-associated cholelithiasis. 9 Komura J. Yano H. Tanaka Y. Tsuru T. Increased incidence of cholestasis during total parenteral nutrition in children – factors affecting stone formation. Kurume Med J. 1993; 40: 7-11 Crossref PubMed Scopus (16) Google Scholar Finally, I will note that the observations by Klek that his and “many” other clinical studies have "proven" SMOFLipid beneficial for the liver as he indicated, are at best, gross exaggerations. If anything, SMOF may have been shown to be safe for the liver, although given the small number of patients in these reports, even that cannot be assumed proven. There are many more things in nutritional science that are unproven than proven, and this is one of those.