To the Editor: Ashen and Blumenthal (Sept. 22 issue)1 statethat caution is recommended with the use of high-dose niacinin patients with diabetes, because niacin may increase glucoselevels. However, the Arterial Disease Multiple InterventionTrial (ADMIT)2 showed that niacin can be used safely in patientswith diabetes. Levels of glycosylated hemoglobin were unchangedfrom baseline in patients with diabetes who were assigned toreceive niacin therapy. In fact, there were no differences inniacin discontinuation, niacin dosage, or hypoglycemic therapyin patients with diabetes who received niacin, as compared withbaseline.
Previous reports of niacin-induced glucose intolerance are derivedlargely from uncontrolled case reports involving small numbersof subjects. Since niacin is effective in treating the dyslipidemia(low levels of high-density lipoprotein [HDL] cholesterol andelevated triglyceride levels) that is commonly seen in patientswith diabetes, this medication should not be withheld becauseof concern about glycemic control.
Marc S. Itskowitz, M.D. Allegheny General Hospital Pittsburgh, PA 15212 mitskowi{at}wpahs.org
References
Ashen MD, Blumenthal RS. Low HDL cholesterol levels. N Engl J Med 2005;353:1252-1260. [Free Full Text]
Elam MB, Hunninghake DB, Davis KB, et al. Effect of niacin on lipid and lipoprotein levels and glycemic control in patients with diabetes and peripheral arterial disease: the ADMIT study: a randomized trial. JAMA 2000;284:1263-1270. [Free Full Text]
To the Editor: Ashen and Blumenthal do not mention a potentiallyimportant ocular side effect of niacin therapy. Niacin has beenlinked to a loss of central vision owing to the developmentof a form of cystoid macular edema.1,2,3 The cystoid macularalterations in niacin maculopathy appear to be biomicroscopicallyidentical to those seen in cystoid macular edema after cataractextraction.2 Cystoid macular edema is usually seen in men betweenthe ages of 30 and 60 years.3 The edema usually resolves whenniacin therapy is stopped.2 Prompt recognition of the associationof visual loss with niacin in patients taking this drug is critical.
Jeffrey L. Pollock, M.D. Hahnemann University Hospital Philadelphia, PA 19102
References
Gass JD. Nicotinic acid maculopathy. Am J Ophthalmol 1973;76:500-510. [Medline]
Fraunfelder FW, Fraunfelder FT, Illingworth DR. Adverse ocular effects associated with niacin therapy. Br J Ophthalmol 1995;79:54-56. [Free Full Text]
Fraunfelder FW. Ocular side effects from herbal medicines and nutritional supplements. Am J Ophthalmol 2004;138:639-647. [Medline]
To the Editor: Ashen and Blumenthal do not correctly describethe effects of dietary fat on low-density lipoprotein (LDL)cholesterol and on HDL cholesterol. HDL cholesterol levels indeeddecline when fat intake is reduced, but when the fat that isreduced is unsaturated, LDL cholesterol levels do not go downbut, rather, go up.1 Such unsaturated fats make up more than60 percent of the fat in the U.S. diet. Moreover, the beneficialeffects of vegetable oils on HDL cholesterol are not specificallydue to their n–3 fatty acid content but to the monounsaturatedfatty acids and n–6 polyunsaturated fatty acids that makeup the bulk of most vegetable oils. The effects of n–3polyunsaturated fatty acids on HDL cholesterol do not differfrom those of other unsaturated fats2; therefore, the high HDLcholesterol levels in Alaskan populations must be due to otherfactors. Finally, the alleged beneficial effect of carbohydrateswith a low glycemic index on HDL cholesterol is only tentativeand still needs to be confirmed in additional randomized trials.
Martijn B. Katan, Ph.D. Wageningen Centre for Food Sciences 6703 HD Wageningen, the Netherlands
References
Mensink RP, Zock PL, Kester ADM, Katan MB. Effects of dietary fatty acids and carbohydrates on the ratio of serum total to HDL cholesterol and on serum lipids and apolipoproteins: a meta-analysis of 60 controlled trials. Am J Clin Nutr 2003;77:1146-1155. [Free Full Text]
Harris WS. n-3 Fatty acids and serum lipoproteins: human studies. Am J Clin Nutr 1997;65:Suppl:1645S-1654S. [Free Full Text]
To the Editor: Ashen and Blumenthal suggest in their illustrationof reverse cholesterol transport that the large intestine isa relevant source of lipid-poor, apolipoprotein A-I–containingpre- HDL cholesterol. Although there is certainly evidence thatcell lines in the fetal human colon1 and in some colon-cancercell lines2 synthesize and secrete apolipoprotein A-I, to ourknowledge there are no data that demonstrate this capacity inthe normal adult colon. Avian species such as chickens synthesizeand secrete apolipoprotein A-I from a variety of extrahepatic,extraintestinal tissues,3 including the colon, but even in chickens,intestinal expression of apolipoprotein A-I messenger RNA ispredominantly restricted to the small intestine. The synthesisof intestinal apolipoprotein A-I in mammals4,5 and, as a corollary,the secretion of pre- HDL cholesterol should be viewed as virtuallyexclusively confined to enterocytes of the small intestine.
Yan Xie, M.D. Nicholas O. Davidson, M.B., B.S., D.Sc. Washington University School of Medicine St. Louis, MO 63110 nod{at}wustl.edu
References
Basque JR, Levy J, Beaulieu J-F, Menard D. Apolipoproteins in human fetal colon: immunolocalization, biogenesis, and hormonal regulation. J Cell Biochem 1998;70:354-365. [CrossRef][Web of Science][Medline]
Reisher SR, Hughes TE, Ordovas JM, Schaefer EJ, Feinstein SI. Increased expression of apolipoprotein genes accompanies differentiation in the intestinal cell line Caco-2. Proc Natl Acad Sci U S A 1993;90:5757-5761. [Free Full Text]
Blue ML, Ostapchuk P, Gordon JS, Williams DL. Synthesis of apolipoprotein AI by peripheral tissues of the rooster: a possible mechanism of cellular cholesterol efflux. J Biol Chem 1982;257:11151-11159. [Free Full Text]
Davidson NO, Glickman RM. Apolipoprotein A-I synthesis in rat small intestine: regulation by dietary triglyceride and biliary lipid. J Lipid Res 1985;26:368-379. [Abstract]
Naganawa S, Ginsberg HN, Glickman RM, Ginsburg GS. Intestinal transcription and synthesis of apolipoprotein AI is regulated by five natural polymorphisms upstream of the apolipoprotein CIII gene. J Clin Invest 1997;99:1958-1965. [Web of Science][Medline]
The authors reply: With regard to niacin therapy: we agree withDr. Itskowitz that such therapy is effective in treating dyslipidemiaand may be used safely in patients with diabetes, as demonstratedin ADMIT. However, we continue to recommend caution in the useof niacin therapy in patients with diabetes, according to therecommendations of the American Diabetes Association,1 as citedin our article. Niacin therapy can result in hyperglycemia andshould be used with caution. Dr. Pollock notes a very importantocular side effect of this therapy — namely, cystoid macularedema. Prompt recognition of visual loss in men between theages of 30 and 60 years who are receiving niacin therapy isof critical importance.
In response to Dr. Katan: we agree that the effects of n–3polyunsaturated fatty acids do not differ from those of otherunsaturated fats and that the high HDL cholesterol levels inAlaskan populations may be due to other factors. We are alsoin agreement that although the dietary glycemic load is negativelycorrelated with HDL cholesterol levels, as mentioned in ourarticle, this relationship needs to be confirmed in additionalrandomized trials.
In response to Drs. Xie and Davidson: we agree that the diagramin our article misrepresents the actual relevant source of lipid-poor,apolipoprotein A-I–containing pre- HDL; it should indicatethe small intestine rather than the large intestine. This wasan oversight on our part. The figure legend indicates "intestinalmucosa" but should more accurately indicate "mucosa of the smallintestine."
Dominique Ashen, Ph.D., C.R.N.P. Roger S. Blumenthal, M.D. Johns Hopkins Ciccarone Center for the Prevention of Heart Disease Baltimore, MD 21287 rblument{at}jhmi.edu
References
Haffner SM. Management of dyslipidemia in adults with diabetes. Diabetes Care 2003;26:Suppl 1:S83-S86.
Correction
to
Ashen and Blumenthal, 
HDL cholesterol. Although there is certainly evidence that cell lines in the fetal human colon1 and in some colon-cancer cell lines2 synthesize and secrete apolipoprotein A-I, to our knowledge there are no data that demonstrate this capacity in the normal adult colon. Avian species such as chickens synthesize and secrete apolipoprotein A-I from a variety of extrahepatic, extraintestinal tissues,3 including the colon, but even in chickens, intestinal expression of apolipoprotein A-I messenger RNA is predominantly restricted to the small intestine. The synthesis of intestinal apolipoprotein A-I in mammals4,5 and, as a corollary, the secretion of pre-
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