Low HDL Cholesterol Levels
http://www.100md.com
《新英格兰医药杂志》
To the Editor: Ashen and Blumenthal (Sept. 22 issue)1 state that caution is recommended with the use of high-dose niacin in patients with diabetes, because niacin may increase glucose levels. However, the Arterial Disease Multiple Intervention Trial (ADMIT)2 showed that niacin can be used safely in patients with diabetes. Levels of glycosylated hemoglobin were unchanged from baseline in patients with diabetes who were assigned to receive niacin therapy. In fact, there were no differences in niacin discontinuation, niacin dosage, or hypoglycemic therapy in patients with diabetes who received niacin, as compared with baseline.
Previous reports of niacin-induced glucose intolerance are derived largely from uncontrolled case reports involving small numbers of subjects. Since niacin is effective in treating the dyslipidemia (low levels of high-density lipoprotein cholesterol and elevated triglyceride levels) that is commonly seen in patients with diabetes, this medication should not be withheld because of concern about glycemic control.
Marc S. Itskowitz, M.D.
Allegheny General Hospital
Pittsburgh, PA 15212
mitskowi@wpahs.org
References
Ashen MD, Blumenthal RS. Low HDL cholesterol levels. N Engl J Med 2005;353:1252-1260.
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.
To the Editor: Ashen and Blumenthal do not mention a potentially important ocular side effect of niacin therapy. Niacin has been linked to a loss of central vision owing to the development of a form of cystoid macular edema.1,2,3 The cystoid macular alterations in niacin maculopathy appear to be biomicroscopically identical to those seen in cystoid macular edema after cataract extraction.2 Cystoid macular edema is usually seen in men between the ages of 30 and 60 years.3 The edema usually resolves when niacin therapy is stopped.2 Prompt recognition of the association of 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.
Fraunfelder FW, Fraunfelder FT, Illingworth DR. Adverse ocular effects associated with niacin therapy. Br J Ophthalmol 1995;79:54-56.
Fraunfelder FW. Ocular side effects from herbal medicines and nutritional supplements. Am J Ophthalmol 2004;138:639-647.
To the Editor: Ashen and Blumenthal do not correctly describe the effects of dietary fat on low-density lipoprotein (LDL) cholesterol and on HDL cholesterol. HDL cholesterol levels indeed decline when fat intake is reduced, but when the fat that is reduced is unsaturated, LDL cholesterol levels do not go down but, rather, go up.1 Such unsaturated fats make up more than 60 percent of the fat in the U.S. diet. Moreover, the beneficial effects of vegetable oils on HDL cholesterol are not specifically due to their n–3 fatty acid content but to the monounsaturated fatty acids and n–6 polyunsaturated fatty acids that make up the bulk of most vegetable oils. The effects of n–3 polyunsaturated fatty acids on HDL cholesterol do not differ from those of other unsaturated fats2; therefore, the high HDL cholesterol levels in Alaskan populations must be due to other factors. Finally, the alleged beneficial effect of carbohydrates with a low glycemic index on HDL cholesterol is only tentative and 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.
Harris WS. n-3 Fatty acids and serum lipoproteins: human studies. Am J Clin Nutr 1997;65:Suppl:1645S-1654S.
To the Editor: Ashen and Blumenthal suggest in their illustration of reverse cholesterol transport that the large intestine is a relevant source of lipid-poor, apolipoprotein A-I–containing pre- 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- HDL cholesterol should be viewed as virtually exclusively 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@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.
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.
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.
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.
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.
The authors reply: With regard to niacin therapy: we agree with Dr. Itskowitz that such therapy is effective in treating dyslipidemia and may be used safely in patients with diabetes, as demonstrated in ADMIT. However, we continue to recommend caution in the use of niacin therapy in patients with diabetes, according to the recommendations of the American Diabetes Association,1 as cited in our article. Niacin therapy can result in hyperglycemia and should be used with caution. Dr. Pollock notes a very important ocular side effect of this therapy — namely, cystoid macular edema. Prompt recognition of visual loss in men between the ages of 30 and 60 years who are receiving niacin therapy is of critical importance.
In response to Dr. Katan: we agree that the effects of n–3 polyunsaturated fatty acids do not differ from those of other unsaturated fats and that the high HDL cholesterol levels in Alaskan populations may be due to other factors. We are also in agreement that although the dietary glycemic load is negatively correlated with HDL cholesterol levels, as mentioned in our article, this relationship needs to be confirmed in additional randomized trials.
In response to Drs. Xie and Davidson: we agree that the diagram in our article misrepresents the actual relevant source of lipid-poor, apolipoprotein A-I–containing pre- HDL; it should indicate the small intestine rather than the large intestine. This was an oversight on our part. The figure legend indicates "intestinal mucosa" but should more accurately indicate "mucosa of the small intestine."
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@jhmi.edu
References
Haffner SM. Management of dyslipidemia in adults with diabetes. Diabetes Care 2003;26:Suppl 1:S83-S86.
Previous reports of niacin-induced glucose intolerance are derived largely from uncontrolled case reports involving small numbers of subjects. Since niacin is effective in treating the dyslipidemia (low levels of high-density lipoprotein cholesterol and elevated triglyceride levels) that is commonly seen in patients with diabetes, this medication should not be withheld because of concern about glycemic control.
Marc S. Itskowitz, M.D.
Allegheny General Hospital
Pittsburgh, PA 15212
mitskowi@wpahs.org
References
Ashen MD, Blumenthal RS. Low HDL cholesterol levels. N Engl J Med 2005;353:1252-1260.
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.
To the Editor: Ashen and Blumenthal do not mention a potentially important ocular side effect of niacin therapy. Niacin has been linked to a loss of central vision owing to the development of a form of cystoid macular edema.1,2,3 The cystoid macular alterations in niacin maculopathy appear to be biomicroscopically identical to those seen in cystoid macular edema after cataract extraction.2 Cystoid macular edema is usually seen in men between the ages of 30 and 60 years.3 The edema usually resolves when niacin therapy is stopped.2 Prompt recognition of the association of 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.
Fraunfelder FW, Fraunfelder FT, Illingworth DR. Adverse ocular effects associated with niacin therapy. Br J Ophthalmol 1995;79:54-56.
Fraunfelder FW. Ocular side effects from herbal medicines and nutritional supplements. Am J Ophthalmol 2004;138:639-647.
To the Editor: Ashen and Blumenthal do not correctly describe the effects of dietary fat on low-density lipoprotein (LDL) cholesterol and on HDL cholesterol. HDL cholesterol levels indeed decline when fat intake is reduced, but when the fat that is reduced is unsaturated, LDL cholesterol levels do not go down but, rather, go up.1 Such unsaturated fats make up more than 60 percent of the fat in the U.S. diet. Moreover, the beneficial effects of vegetable oils on HDL cholesterol are not specifically due to their n–3 fatty acid content but to the monounsaturated fatty acids and n–6 polyunsaturated fatty acids that make up the bulk of most vegetable oils. The effects of n–3 polyunsaturated fatty acids on HDL cholesterol do not differ from those of other unsaturated fats2; therefore, the high HDL cholesterol levels in Alaskan populations must be due to other factors. Finally, the alleged beneficial effect of carbohydrates with a low glycemic index on HDL cholesterol is only tentative and 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.
Harris WS. n-3 Fatty acids and serum lipoproteins: human studies. Am J Clin Nutr 1997;65:Suppl:1645S-1654S.
To the Editor: Ashen and Blumenthal suggest in their illustration of reverse cholesterol transport that the large intestine is a relevant source of lipid-poor, apolipoprotein A-I–containing pre- 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- HDL cholesterol should be viewed as virtually exclusively 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@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.
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.
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.
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.
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.
The authors reply: With regard to niacin therapy: we agree with Dr. Itskowitz that such therapy is effective in treating dyslipidemia and may be used safely in patients with diabetes, as demonstrated in ADMIT. However, we continue to recommend caution in the use of niacin therapy in patients with diabetes, according to the recommendations of the American Diabetes Association,1 as cited in our article. Niacin therapy can result in hyperglycemia and should be used with caution. Dr. Pollock notes a very important ocular side effect of this therapy — namely, cystoid macular edema. Prompt recognition of visual loss in men between the ages of 30 and 60 years who are receiving niacin therapy is of critical importance.
In response to Dr. Katan: we agree that the effects of n–3 polyunsaturated fatty acids do not differ from those of other unsaturated fats and that the high HDL cholesterol levels in Alaskan populations may be due to other factors. We are also in agreement that although the dietary glycemic load is negatively correlated with HDL cholesterol levels, as mentioned in our article, this relationship needs to be confirmed in additional randomized trials.
In response to Drs. Xie and Davidson: we agree that the diagram in our article misrepresents the actual relevant source of lipid-poor, apolipoprotein A-I–containing pre- HDL; it should indicate the small intestine rather than the large intestine. This was an oversight on our part. The figure legend indicates "intestinal mucosa" but should more accurately indicate "mucosa of the small intestine."
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@jhmi.edu
References
Haffner SM. Management of dyslipidemia in adults with diabetes. Diabetes Care 2003;26:Suppl 1:S83-S86.