Preliminary Observations

Short term hypercholesterolemic effects of oral L. sporogenes therapy (360 million spores/day in tablet form) Were studied in 17
patients with type II hyperlipidemia in an open label fixed dose trial. Total serum cholesterol (330 ±55mg/dl vs 226 ±46 mg/dl, P<
0.001), LDL-cholesterol (267± 58 mg/dl vs 173±54 mg/dl, (P< 0.001) and total cholesterol to HDL cholesterol and LDL-
cholesterol to HDL- cholesterol ratios (P< 0.001) were reduced significantly over a period of three months. HDL cholesterol was
marginally increased (43.6±7 mg/dl vs 46.8±8.9 mg/dl, P <0.05); however there was no change in serum triglyceride levels.

Primary hypercholesterolemia imposes a significantly enhanced risk of morbidity and mortality from coronary artery disease.
The most recent primary prevention trials 1,2 demonstrated that pharmacological intervention can significantly lower this risk by
modifying serum lipoproteins. Search for a safe, effective and inexpensive pharmacological agent continues. Bile salt
sequestrants have been frequently used in the treatment of hyperlipidemia by interfering with the enterohepatic circulation of the
bile salts3. However, bile salt binding resins are expensive, unpalatable and frequently cause gastric upsets. Implantation of a
large number of non-pathogenic Lactobacilli in the proximal small intestine to facilitate deconjugation of bile salts and
degradation of free cholesterol by the bacterial enzymes is an attractive alternative method for this purpose. Lactobacillus
sporogenes, spore-forming gram positive aerobe, germinates into the vegetative form in the proximal small intestine bypassing
the gastric acid when taken orally in tablet form. This study was undertaken to test the hypothesis that implantation of these
non-pathogenic normal flora in large numbers could be an effective and safe method of treating patients with primary
dyslipidemia.

Materials & Methods
A total of 20 patients with primary hyperlipidemia were enrolled for this study, of whom 17 completed the trial. These included 15
men and two women aged 32-61 yr. (mean 45.6 yr.). Inclusion criteria were (i) total serum cholesterol > 240 mg/dl; (ii)
LDL-cholesterol >200 mg/dl; and (iii) three months trials with non-pharmacological treatment without apparent decrease in
serum lipids. The study design involved an open label, non-randomised fixed dose trial. The active drug was administered orally
in a dose of two tablets (60 million spores tablet) three a day. Detailed serum lipid estimation was done in a central laboratory,
twice during initial screening period and later after 0, 4, 8 and 12 wk of therapy. The methods employed4 have already been
validated in our laboratory. The coefficients of variation of the two samples drawn in the initial screening phase for all the
patients were 6.6 % for total cholesterol, 4.3% for HDL-cholesterol and 1.7% for triglycerides. At each 4-weekly visit, the patients
underwent physical and routine biochemical examination and were asked about adverse effects and drug compliance.

Results & Discussion
Serum lipid levels before and after treatment are shown in the Table. There was a highly significant reduction in total and
LDL-cholesterol levels (31.5% and 35.2% respectively, P<0.001) following therapy. A small but significant increase was
observed in HDL-cholesterol (7.2%, P<0.05). There was no change in serum triglyceride levels. Atherogenic lipid ratios were
also decreased following treatment (total/HDL-cholesterol by 24% and LDL/HDL cholesterol by 33.4%, P<0.001; Fig.). No
adverse effects were noted except constipation in one patient.

L. sporogenes therapy proved an effective hypolipidemic agent in this preliminary short term trial. The study however, had the
following limitations (i) it is a preliminary study in a small number of patients followed for three months only; (ii) it is also an
open, non-randomised trial without control; (iii) no attempt has been made to elucidate the mechanism of action; and (iv)
bio-chemical methods used in this study for lipid estimation are known to have some inherent limitations. Further studies are
necessary to establish the mechanism of action and efficacy in larger number of patients before it is accepted as an alternative
mode of treatment of patients with hyperlipidemias.

Acknowledgement
The authors thank Dr. Triloki Nath of the Biochemistry Department of this hospital for carrying out lipid analysis. The financial
assistance and supply of Sporlac tablets by Uni Sankyo, is acknowledged.

References
Lipid Research Clinics Program: The lipid research clinics coronary primary prevention trial II. The relationship of reduction in
incidence of coronary heart disease to cholesterol lowering JAMA 251 (1984) 365.
Frick, M.H., Elo, O., Haapa, K., Heinonen, O.P. Heinsalmi, P., Manninen, V., Maenpaa, H., Malkoned, H., Manttari, M., Norola, S.,
Pasternack, A., Pikkarained, J., Romo, M., Sjoblom, T. and Nikkila, E.A. Hensink Heart Study: primary prevention trial with
gemfibroz in middle-aged men with dyslipidemia. Safety of treatment, changes in risk factors and incidence of coronary heart
disease. N Engl J Med 317 (1987) 1237.
Brensike, J.F., Levy, R.I., Kelsey, S.F., Passamani, E.R., Richardson, J.M., Loh, I.K., Stone, N.J., Aldrich, R.F., Battaglini, J.W.,
Moriarty, D.J., Fisher, M.R., Friedman, L., Friedewald, W., Detre, K.M. and Epstein, S.E. Effects of therapy with cholestyramine on
progression of coronary atheriosclerosis: results of the NHLBI type II coronary intervention study. Circulation 69 (1984) 313.
Haux, P. and Natelson, S. Microprocedure. Microbet. J16 (1971) 68.

J.C Mohan, R. Arora &M. Khalilullah
Department of Cardiology, G.B. Pant Hospital, New Delhi

Accepted June 19, 1990

<<< BACK TO LIBRARY