[Skip to Content]
[Skip to Content Landing]
Article
May 1961

Treatment of Hypercholesteremia by Nicotinic Acid: Progress Report with Review of Studies Regarding Mechanism of Action

Author Affiliations
MADISON, WIS.
Jackson Clinic and Foundation.
Arch Intern Med. 1961;107(5):639-652. doi:10.1001/archinte.1961.03620050005002
Abstract

Introduction  The use of nicotinic acid in large doses has gained wide recognition as a means of reducing serum cholesterol levels without dietary restriction.1,2 The greatest reduction occurs in the β-lipoprotein cholesterol fraction, with an increase in the α1-lipoprotein cholesterol fraction.3,4 Both free and esterified cholesterol fractions are reduced.5 Total lipids, fatty acids, and triglycerides decrease in the same manner as cholesterol.3,5-8 Fatty acids and triglycerides are reduced.5,6,8 Phospholipids are reduced perhaps proportionately less than other lipids.3,5It is well to emphasize that there is no definite evidence that reduction in serum cholesterol levels in humans will result in retardation of atherogenesis or in removal of existing atheromata. However, it seems reasonable to study any method of reducing serum cholesterol levels to determine its efficacy, its safety, and its ultimate effect on the arteries. Studies of toxicity must include not only the

References
1.
I am grateful for statistical consultation by Dr. Klaus Patau of the University of Wisconsin.
2.
Aluminum nicotinate was supplied by the Walker Laboratories, Mount Vernon, N.Y.
3.
Ahrens, E. H., Jr., et al.:  Symposium on Significance of Lowered Cholesterol Levels, American Medical Association, Council on Foods and Nutrition ,  J.A.M.A. 170:2198-2203 ( (Aug. 29) ) 1959.Crossref
4.
Portman, O. W., and Stare, F. J.:  Dietary Regulation of Serum Cholesterol Levels ,  Physiol. Rev. 39:407-442 ( (July) ) 1959.
5.
Parsons, W. B., Jr.; Achor, R. W. P.; Berge, K. G.; McKenzie, B. F., and Barker, N. W.:  Changes in Concentration of Blood Lipids Following Prolonged Administration of Large Doses of Nicotinic Acid to Persons with Hypercholesterolemia ,  Proc. Mayo Clin. 31:377-390 ( (June 27) ) 1956.
6.
Parsons, W. B., Jr., and Flinn, J. H.:  Reduction of Serum Cholesterol Levels and Beta-Lipoprotein Cholesterol Levels by Nicotinic Acid ,  A.M.A. Arch. Intern. Med. 103:783-790 ( (May) ) 1959.Crossref
7.
Gurian, H., and Adlersberg, D.:  The Effect of Large Doses of Nicotinic Acid on Circulating Lipids and Carbohydrate Tolerance ,  Amer. J. Med. Sci. 237:12-22 ( (Jan.) ) 1959.Crossref
8.
DeSoldati, L.; Stritzler, G., and Balassanian, S.:  Acción del ácido nicotinico sobre les lipidos de la sangre en pacientes arterioscleróticos ,  Prensa Med. Argent. 44:3286-3292 ( (Nov. 8) ) 1957.
9.
Galbraith, P. A.; Perry, W. F., and Beamish, R. E.:  Effect of Nicotinic Acid on Serum Lipids in Normal and Atherosclerotic Subjects ,  Lancet 1: 222-223 ( (Jan. 31) ) 1959.Crossref
10.
Miller, O. N.; Hamilton, J. G., and Goldsmith, G. A.:  Investigation of the Mechanism of Action of Nicotinic Acid on Serum Lipid Levels in Man ,  Amer. J. Clin. Nutr. 8:480-490 ( (July) -Aug.) 1960.
11.
Parsons, W. B., Jr., and Flinn, J. H.:  Reduction in Elevated Blood Cholesterol Levels by Large Doses of Nicotinic Acid ,  J.A.M.A. 165: 234-238 ( (Sept. 21) ) 1957.Crossref
12.
Sperry, W. M., and Webb, M.:  A Revision of the Schoenheimer-Sperry Method for Cholesterol Determination ,  J. Biol. Chem. 187:97-106 ( (Nov.) ) 1950.
13.
Zak, B.; Dickennian, R. C.; White, E. G.; Burnett, H., and Cherney, P. J.:  Rapid Estimation of Free and Total Cholesterol ,  Amer. J. Clin. Path. 24:1307-1315 ( (Nov.) ) 1954.
14.
Altschul, R.:  Die Beeinflussung des Blutcholesterinspiegels und der experimentellen Atherosklerose durch Nikotinsäure ,  Z. Kreislaufforsch. 45:573-576 ( (Aug.) ) 1956.
15.
Cava, E. E.; Achor, R. W. P.; Berge, K. G.; Wakim, K. G.; Edwards, J. E.; McKenzie, B. F., and Barker, N. W.:  Effect of Nicotinic Acid on Experimental Atheromatosis of Rabbits ,  Proc. Mayo Clin. 34:502-509 ( (Oct. 14) ) 1959.
16.
Merrill, J. M., and Lemley-Stone, J.:  Effects of Nicotinic Acid on Serum and Tissue Cholesterol in Rabbits ,  Circulat. Res. 5:617-619 ( (Nov.) ) 1957.Crossref
17.
Achor, R. W. P.: Personal communication to the author.
18.
Adlersberg, D.: Personal communication to the author.
19.
O'Reilly, P. O.:  Some Clinical Aspects of Nicotinic Acid Therapy in Hypercholesterolaemia ,  Canad. Med. Ass. J. 78:402-405 ( (March 15) ) 1958.
20.
Parsons, W. B., Jr.:  Use of Aluminum Nicotinate in Hypercholesterolemia ,  Curr. Ther. Res. 2:137-143 ( (May) ) 1960.
21.
Parsons, W. B., Jr.:  Activation of Peptic Ulcer by Nicotinic Acid: Report of 5 Cases ,  J.A.M.A. 173:1466-1470 ( (July 30) ) 1960.Crossref
22.
Ruiter, M., and Meyler, L.:  Huidveranderingen na therapeutische toediening van nicotinezuur in hoge dosering ,  Ned. T. Geneesk. 104:1114-1116 ( (June) ) 1960.
23.
Parsons, W. B., Jr.: Studies of Nicotinic Acid Use in Hypercholesteremia: Changes in Hepatic Function, Carbohydrate Tolerance, and Uric Acid Metabolism, this issue, page 653.
24.
Weiner, M.; deCrinis, K.; Redisch, W., and Steele, J. M.:  Influence of Some Vasoactive Drugs on Fibrinolytic Activity ,  Circulation 19:845-848 ( (June) ) 1959.Crossref
25.
Weiner, M.; Redisch, W., and Steele, J. M.:  Occurrence of Fibrinolytic Activity Following Administration of Nicotinic Acid ,  Proc. Soc. Exp. Biol. Med. 98:755-757 ( (Aug.) -Sept.) 1958.Crossref
26.
Wilson, W. L., and Fostiropoulos, G.:  Observations on the Use of Nicotinic Acid to Induce in Vivo Fibrinolytic Activity ,  Amer. J. Med. Sci. 238:591-597 ( (Nov.) ) 1959.Crossref
27.
Parsons, W. B., Jr.:  Production of Fibrinolysin Following Administration of Nicotinic Acid in Humans ,  Circulation , to be published.
28.
Duncan, C. H., and Best, M. M.:  Lack of Nicotinic Acid Effect on Cholesterol Metabolism of the Rat ,  J. Lipid Res. 1:159-163 ( (Jan.) ) 1960.
29.
Friedman, M., and Byers, S. O.:  Evaluation of Nicotinic Acid as an Hypocholesteremic and Anti-Atherogenic Substance ,  J. Clin. Invest. 38: 1328-1333 ( (Aug.) ) 1959.Crossref
30.
Gaylor, J. L.; Hardy, R. W. F., and Baumann, C. A.:  Effects of Nicotinic Acid and Related Compounds on Sterol Metabolism in the Chick and Rat ,  J. Nutr. 70:293-301 ( (March) ) 1960.
31.
Hardy, R. W. F.; Gaylor, J. L., and Baumann, C. A.:  Biosynthesis of Sterols and Fatty Acids as Affected by Nicotinic Acid and Related Compounds ,  J. Nutr. 71:159-167 ( (June) ) 1960.
32.
Nath, N.; Harper, A. E., and Elvehjem, C. A.:  Diet and Cholesteremia: IV. Effects of Carbohydrate and Nicotinic Acid ,  Proc. Soc. Exp. Biol. Med. 102:571-574 ( (Dec.) ) 1959.Crossref
33.
Kritchevsky, D.; Whitehouse, M. W., and Staple, E.:  Oxidation of Cholesterol-26-C14 by Rat Liver Mitochondria: Effect of Nicotinic Acid ,  J. Lipid Res. 1:154-156 ( (Jan.) ) 1960.
34.
Perry, W. F.:  Effect of Nicotinic Acid and Nicotinamide on Incorporation of Acetate into Cholesterol, Fatty Acids and CO2 by Rat Liver Slices ,  Metabolism 9:686-689 ( (July) ) 1960.
35.
Norcia, L. N.; Brown, H. J., and Furman, R. H.:  Non-Hypocholesterolaemic Action of Nicotinic Acid in Dogs ,  Lancet 1:1255 ( (June 13) ) 1959.Crossref
36.
Grande, F., and Amatuzio, D. S.:  Nicotinic Acid and Serum Cholesterol in the Dog ,  Fed. Proc. 19:237, 1960.
37.
Comesana, F.; Nova, A.; Fishleder, B. L., and Sodi-Pallares, D.:  The Hypocholesterolemic Effect of Nicotinic Acid ,  Amer. Heart J. 55: 476-480 ( (March) ) 1958.Crossref
38.
Parsons, W. B., Jr.: Unpublished observations.
39.
Olson, R. E.: Personal communication to the author.
40.
Schade, H., and Saltman, P.:  The Influence of Nicotinic Acid on Hepatic Cholesterol Synthesis in Rabbits ,  Proc. Soc. Exp. Biol. Med. 102:265-267 ( (Nov.) ) 1959.Crossref
41.
Hardy, R. W. F.; Gaylor, J. L., and Baumann, C. A.: Unpublished observations.
42.
Kraupp, O., and Schnetz, E.:  Der Einfluss des Heparins auf die hypocholesterinämische Wirkung der Nicotinsäure ,  Naunyn Schmiedeberg Arch. Exp. Path. 235:103-112, 1959.
43.
Kraupp, O.; Schnetz, E., and Stormann, H.:  Untersuchungen über den Mechanismus der hypocholesterinämischen Wirkung der Nikotinsäure ,  Z. Ges. Exp. Med. 129:601-614, 1958.Crossref
44.
Altschul, R.; Hoffer, A., and Stephen, J. D.:  Influence of Nicotinic Acid on Serum Cholesterol in Man ,  Arch. Biochem. 54:558-559 ( (Feb.) ) 1955.Crossref
×