Logo of jcinvestThe Journal of Clinical InvestigationCurrent IssueArchiveSubscriptionAbout the Journal
J Clin Invest. May 1979; 63(5): 858–867.
PMCID: PMC372026

Effects of Nicotinic Acid Therapy on Plasma High Density Lipoprotein Subfraction Distribution and Composition and on Apolipoprotein A Metabolism


This report describes the effects of pharmacologic doses (3 g/d) of nicotinic acid on the plasma distribution and chemical composition of the high density lipoprotein (HDL) subfractions HDL2 and HDL3 and examines the influence of the drug on the metabolism of the major HDL apoproteins, apolipoproteins A-I (ApoA-I) and A-II (Apo-II).

The drug lowered plasma cholesterol (15%, P < 0.05) and triglyceride (27%, P < 0.01); the former effect a result of a fall in the amount of cholesterol associated with very low density lipoproteins (31%, P < 0.02) and low density lipoproteins (36%, P < 0.02). Conversely, it raised plasma HDL cholesterol (23%, P < 0.05) and increased (by 345%) the plasma HDL2:HDL3 ratio. The latter derived from an absolute increment (646%) in circulating HDL2, coupled with a fall (47%) in HDL3. This change was not associated with major alterations in the overall cholesterol (free and esterified), triglyceride, phospholipid, or protein content of the subfractions; however, it was accompanied by substantial changes in their protein composition. In particular, the molar ratio of ApoA-I:ApoA-II in HDL3 declined from 2.7:1 to 2.1:1 during nicotinic acid treatment.

Significant perturbations of ApoA-I and ApoA-II metabolism accompanied the drug-induced HDL subfraction redistribution. Specifically, the plasma concentration of ApoA-I rose by 7% (P < 0.05) because of a decrease in its fractional catabolic rate. Moreover, whereas before treatment 6 and 94% of the plasma ApoA-I circulated with HDL2 and HDL3, after commencement of nicotinic acid therapy this distribution became 49 and 51% in HDL2 and HDL3, respectively. ApoA-II was found mainly in HDL3, both before and during nicotinic acid treatment. Administration of the drug caused a 14% reduction in its plasma concentration (P < 0.05), which derived principally from a fall (22%, P < 0.01) in its synthetic rate.

These data suggest that the effects of nicotinic acid on the HDL subfraction distribution may be mediated via (a) net transfer of ApoA-I from HDL3 to HDL2 and (b) a reduction in ApoA-II synthesis. Our present understanding of the association between HDL and atherosclerosis indicates that such changes may have prophylactic value in the prevention of coronary artery disease.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.3M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Miller NE, Thelle DS, Forde OH, Mjos OD. The Tromsø heart-study. High-density lipoprotein and coronary heart-disease: a prospective case-control study. Lancet. 1977 May 7;1(8019):965–968. [PubMed]
  • Gordon T, Castelli WP, Hjortland MC, Kannel WB, Dawber TR. High density lipoprotein as a protective factor against coronary heart disease. The Framingham Study. Am J Med. 1977 May;62(5):707–714. [PubMed]
  • Rhoads GG, Gulbrandsen CL, Kagan A. Serum lipoproteins and coronary heart disease in a population study of Hawaii Japanese men. N Engl J Med. 1976 Feb 5;294(6):293–298. [PubMed]
  • Castelli WP, Doyle JT, Gordon T, Hames CG, Hjortland MC, Hulley SB, Kagan A, Zukel WJ. HDL cholesterol and other lipids in coronary heart disease. The cooperative lipoprotein phenotyping study. Circulation. 1977 May;55(5):767–772. [PubMed]
  • KANNEL WB, KAGAN A, DAWBER TR, REVOTSKIE N. Epidemiology of coronary heart disease. Implications for the practicing physician. Geriatrics. 1962 Oct;17:675–690. [PubMed]
  • Cheung MC, Albers JJ. The measurement of apolipoprotein A-I and A-II levels in men and women by immunoassay. J Clin Invest. 1977 Jul;60(1):43–50. [PMC free article] [PubMed]
  • Miller GJ, Miller NE. Plasma-high-density-lipoprotein concentration and development of ischaemic heart-disease. Lancet. 1975 Jan 4;1(7897):16–19. [PubMed]
  • Blum CB, Levy RI, Eisenberg S, Hall M, 3rd, Goebel RH, Berman M. High density lipoprotein metabolism in man. J Clin Invest. 1977 Oct;60(4):795–807. [PMC free article] [PubMed]
  • Patsch JR, Yeshurun D, Jackson RL, Gotto AM., Jr Effects of clofibrate, nicotinic acid and diet on the properties of the plasma lipoproteins in a subject with type III hyperlipoproteinemia. Am J Med. 1977 Dec;63(6):1001–1009. [PubMed]
  • Kostner GM, Patsch JR, Sailer S, Braunsteiner H, Holasek A. Polypeptide distribution of the main lipoprotein density classes separated from human plasma by rate zonal ultracentrifugation. Eur J Biochem. 1974 Jun 15;45(2):611–621. [PubMed]
  • Shepherd J, Packard CJ, Patsch JR, Gotto AM, Jr, Taunton OD. Metabolism of apolipoproteins A-I and A-II and its influence on the high density lipoprotein subfraction distribution in males and females. Eur J Clin Invest. 1978 Jun;8(3):115–120. [PubMed]
  • Packard CJ, Third JL, Shepherd J, Lorimer AR, Morgan HG, Lawrie TD. Low density lipoprotein metabolism in a family of familial hypercholesterolemic patients. Metabolism. 1976 Sep;25(9):995–1006. [PubMed]
  • Shepherd J, Gotto AM, Jr, Taunton OD, Caslake MJ, Farish E. The in vitro interaction of human apolipoprotein A-I and high density lipoproteins. Biochim Biophys Acta. 1977 Dec 21;489(3):486–501. [PubMed]
  • Shepherd J, Packard CJ, Gotto AM, Jr, Taunton OD. A comparison of two methods to investigate the metabolism of human apolipoproteins A-I and and A-II. J Lipid Res. 1978 Jul;19(5):656–661. [PubMed]
  • MATTHEWS CM. The theory of tracer experiments with 131I-labelled plasma proteins. Phys Med Biol. 1957 Jul;2(1):36–53. [PubMed]
  • Shepherd J, Packard CJ, Patsch JR, Gotto AM, Jr, Taunton OD. Effects of dietary polyunsaturated and saturated fat on the properties of high density lipoproteins and the metabolism of apolipoprotein A-I. J Clin Invest. 1978 Jun;61(6):1582–1592. [PMC free article] [PubMed]
  • Patsch JR, Sailer S, Kostner G, Sandhofer F, Holasek A, Braunsteiner H. Separation of the main lipoprotein density classes from human plasma by rate-zonal ultracentrifugation. J Lipid Res. 1974 Jul;15(4):356–366. [PubMed]
  • LOWRY OH, ROSEBROUGH NJ, FARR AL, RANDALL RJ. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed]
  • BARTLETT GR. Phosphorus assay in column chromatography. J Biol Chem. 1959 Mar;234(3):466–468. [PubMed]
  • Havel RJ, Kane JP, Kashyap ML. Interchange of apolipoproteins between chylomicrons and high density lipoproteins during alimentary lipemia in man. J Clin Invest. 1973 Jan;52(1):32–38. [PMC free article] [PubMed]
  • ALTSCHUL R, HOFFER A, STEPHEN JD. Influence of nicotinic acid on serum cholesterol in man. Arch Biochem Biophys. 1955 Feb;54(2):558–559. [PubMed]
  • Carlson LA, Orö L, Ostman J. Effect of nicotinic acid on plasma lipids in patients with hyperlipoproteinemia during the first week of treatment. J Atheroscler Res. 1968 Jul-Aug;8(4):667–677. [PubMed]
  • Carlson LA, Olsson G, Ballantyne D. On the rise in low density and high density lipoproteins in response to the treatment of hypertriglyceridaemias in type IV and type V hyperlipoproteinaemias. Atherosclerosis. 1977 Apr;26(4):603–609. [PubMed]
  • Schaefer EJ, Jenkins LL, Brewer HB., Jr Human chylomicron apolipoprotein metabolism. Biochem Biophys Res Commun. 1978 Jan 30;80(2):405–412. [PubMed]
  • Bilheimer DW, Eisenberg S, Levy RI. The metabolism of very low density lipoprotein proteins. I. Preliminary in vitro and in vivo observations. Biochim Biophys Acta. 1972 Feb 21;260(2):212–221. [PubMed]
  • Eisenberg S, Bilheimer DW, Levy RI. The metabolism of very low density lipoprotein proteins. II. Studies on the transfer of apoproteins between plasma lipoproteins. Biochim Biophys Acta. 1972 Sep 7;280(1):94–104. [PubMed]
  • Shepherd J, Patsch JR, Packard CJ, Gotto AM, Jr, Taunton OD. Dynamic properties of human high density lipoprotein apoproteins. J Lipid Res. 1978 Mar;19(3):383–389. [PubMed]

Articles from The Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • Cited in Books
    Cited in Books
    PubMed Central articles cited in books
  • Compound
    PubChem Compound links
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...