LP(a) and Vitamin C

[Dolev]

Owen or anyone. Please comment on this study, which found no effect of ascorbate on LP(a) levels.

Pharmacotherapy. 1995 Jul-Aug;15(4):458-64.

The effect of high-dose ascorbate supplementation on plasma lipoprotein(a) levels in patients with premature coronary heart disease.
Bostom AG, Hume AL, Eaton CB, Laurino JP, Yanek LR, Regan MS, McQuade WH, Craig WY, Perrone G, Jacques PF.

Department of General Internal Medicine, Rhode Island Hospital, Providence, USA.

Abstract
STUDY OBJECTIVE: To determine the efficacy of high-dose ascorbate supplementation in lowering lipoprotein(a) [Lp(a)] levels in patients with premature coronary heart disease (CHD). DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Outpatient clinic. PATIENTS: Forty-four patients with documented premature CHD, defined as confirmed myocardial infarction and/or angiographically determined stenosis of 50% or greater in at least one major coronary artery before age 60 years. INTERVENTIONS: Patients were block randomized on the basis of age, gender, and screening Lp(a) concentrations to receive ascorbate 4.5 g/day or placebo for 12 weeks. MEASUREMENTS AND MAIN RESULTS: High-dose ascorbate was well tolerated and produced a marked elevation in mean plasma ascorbate levels (+1.2 mg/dl; p < 0.001). Multiple linear regression analysis revealed no significant effect of supplementation on postintervention Lp(a) levels (p = 0.39) in a model that included treatment group assignment, and baseline Lp(a) levels. CONCLUSIONS: Our findings do not support a clinically important lowering effect of high-dose ascorbate on plasma Lp(a) in patients with premature CHD.

PMID: 7479198 [PubMed - indexed for MEDLINE

[ofonorow]

It is funny, I have in my files (somewhere) my email correspondence with Dr. Bostom after that study (or a very similar one in JAMA) was published. (The salient point is that he was willing to respond.) I do not remember the particulars, but I may have asked how they measured Lp(a). Clearly, if his results are accurate and fairly reported, then Lp(a) is not generally affected by a reasonable dose of vitamin C for 12 weeks (4 months). I wish they had allowed the study to continue. Also, I believe these were heart patients and therefore on a myriad of drugs, whereas most of our experience is with people weaning themselves from their heart drugs.

Here is another study in which Bostom partipated.

Bostom AG; Cupples LA; Jenner JL; Ordovas JM; Seman LJ; Wilson PW; Schaefer EJ; Castelli WP (1996). Elevated plasma lipoprotein(a) and coronary heart disease in men aged 55 years and younger. A prospective study. Framingham Study, Epidemiology and Biometry Program, Framingham, Mass, USA. JAMA 1996 Aug 21;276(7):544-8.

Abstract

OBJECTIVE: To establish whether elevated lipoprotein(a) [Lp(a)], detected as a sinking pre-beta-lipoprotein band on electrophoresis of fresh plasma, is an independent risk factor for the development of premature coronary heart disease (CHD) in men. DESIGN AND SETTING: Prospective study of the Framingham offspring cohort. PARTICIPANTS: A total of 2191 men aged 20 to 54 years old who were free of cardiovascular disease when they were examined between 1971 and 1975. MAIN OUTCOME MEASURES: Incident CHD (myocardial infarction, coronary insufficiency, angina pectoris, or sudden cardiac death) occurring by age 55 years. RESULTS: After a median follow-up of 15.4 years, there were 129 CHD events. The relative risk (RR) estimates (with 95% confidence intervals [CIs]) for premature CHD derived from a proportional hazards model that included age, body mass index, and the dichotomized risk factor covariables elevated plasma Lp(a) level, total cholesterol level of 6.2 mmol/L (240 mg/dL) or more, high-density lipoprotein (HDL) level less than 0.9 mmol/L (35 mg/dL), smoking, glucose intolerance, and hypertension were as follows: elevated Lp(a) level, RR, 1.9 (95% CI, 1.2-2.9), prevalence, 11.3%; total cholesterol level of 6.2 mmol/L or more, RR, 1.8 (95% CI, 1.2-2.7), prevalence, 14.3%; HDL level of less than 0.9 mmol/L, RR, 1.8 (95% CI, 1.2-2.6), prevalence 19.2%; smoking, RR 3.6 (95% CI, 2.2-5.5), prevalence, 46.7%; glucose intolerance, RR, 2.7 (95% CI, 1.4-5.3), prevalence, 2.6%; hypertension, RR, 1.2 (95% CI, 0.8-1., prevalence, 26.3%. CONCLUSIONS: Elevated plasma Lp(a) is an independent risk factor for the development of premature CHD in men, comparable in magnitude and prevalence (ie, attributable risk) to a total cholesterol level of 6.2 mmol/L (240 mg/dL) or more, or an HDL level less than 0.9 mmol/L (35 mg/dL).

p.s. and my memory is coming back. Our decade long our observations are not generally that vitamin C alone lowers Lp(a), at least not for a long while, and probably not even vitamin C and lysine. However, anecdotally, when proline is added, Lp(a) does decline. I remember the New York medical school professor who began measuring his own Lp(a) and ran a controlled experiment on himself. His elevated Lp(a) dropped about 30% in six months on vitamin C and lysine, which was encouraging, but after he added proline - 14 months later - his Lp(a) was zero. That is when he called me, and I remember that proline can interfere with the production of Lp(a) in the liver by inhibiting the binding of the sticky apo(a) to LDL cholesterol molecules.

[ofonorow]

Also, ran across http://www.ncbi.nlm.nih.gov/pubmed/12052486
Lipoprotein (a) as a predictor of coronary heart disease: the PRIME Study.

Lp(a) appeared a significant risk factor (P<0.0006) in the whole cohort without between-population interaction, even if the association was not statistically significant in the Belfast sample. The relative risk (RR) of CHD events in subjects with Lp(a) levels in the highest quartile was 1.5 times that of subjects in the lowest quartile (RR: 1.56; 95% confidence intervals (CIs): 1.10-2.21). A high Lp(a) level was a risk for MI, coronary death and angina pectoris. A significant interaction term between Lp(a) and LDL-cholesterol levels, however, was found. The relative CHD risk associated with a Lp(a) level > or =33 mg/dl in comparison with Lp(a) <33 mg/dl increasing gradually from 0.82 (95% CI: 0.28-2.44) in men with LDL-cholesterol in the lowest quartile (<121 mg/dl) to 1.58 (95% CI: 1.06-2.40) in the highest quartile (>163 mg/dl). In conclusion, Lp(a) increased the risk for MI and angina pectoris, especially in men with a high LDL-cholesterol level. This study which analyzed Lp(a) level using a measurement independent of apolipoprotein (a) size on fresh plasma, has confirmed utility of Lp(a) as a predictor of CHD.