Davis W, Rockway S, Kwasny M. Effect of a combined therapeutic approach of intensive lipid management, omega-3 fatty acid supplementation, and increased serum 25(OH) vitamin D on coronary calcium scores in asymptomatic adults. Am J Ther. 2009;16(4):326-332.
Unblinded retrospective analysis of data from clinical interventions
Forty-five adults with coronary calcium scores (CCS) ≥50
Study Medication and Dosage
Participants were encouraged to eat a low saturated‒fat, high-fiber, low glycemic‒index diet. Statin doses were individually tailored to reduce low-density lipoprotein (LDL) levels to a maximum of 60 mg/dL. (To meet this criterion, all female subjects and 77% of male subjects required at least some use of statins.) Most subjects also received time-release niacin at unspecified doses.
Additional supplementation consisted of 2,000 IU per day vitamin D3 initially, increased as needed to achieve 25(OH)D3 serum levels between 50 and 60 ng/mL (average dose of vitamin D: 3,590 IU/d). Fish oil was supplemented in varying doses (4 g-10 g/d; average dose: 4.8 g/d) to lower triglycerides (TG) to ≤60 mg/dL. Fish oil supplements contained a minimum of 30% omega-3 fatty acids. A mean of 18 months passed between the initial and final computed tomography (CT) scan reports.
Primary Outcome Measures
Total cholesterol (TC), LDL, high-density lipoprotein cholesterol (HDL), TG, and CCS (as calculated from before-and-after CT scans of the heart) were measured at baseline and at the completion of the trial.
As a function of the combined use of statins plus supplements, TC declined by 24%, LDL declined by 41%, TG declined by 42%, and HDL increased by 19%. Except for the increase in HDL observed in female subjects (11 mg/dL), these changes attained statistical significance.
After 18 months, 20 of the 45 participants experienced an average CCS decline (improvement) of 14.5%, and all but 3 of the remaining subjects experienced either no change in CCS or a relatively slow rate of progression (averaging 12%). A substantial decline in CCS occurred in 44% of subjects and a slowed plaque growth occurred in an additional 49%. These changes in CCS were statistically significant when participants were divided into 3 subgroups based upon the rate of change in CCS: “typical” progression (>29% progression/y), “slowed” progression (<29% progression/y), and the combination of subjects showing no progression and those experiencing actual regression.
Increasingly, researchers are accepting CCS as an indicator of coronary risk and more specifically atherosclerotic progression. When administered alone, statin drugs lower cholesterol but have not been found to reduce CCS or even slow its progression, suggesting that these drugs may not be halting atherosclerotic plaque formation. Despite this limitation, statin therapy has been shown to reduce both the incidence of myocardial infarction and death from coronary artery disease. Nonetheless, the apparent inability of statins to improve CCS suggests that their therapeutic effect may not be optimal.
And what triggered the inclusion of these particular nutritional supplements? Vitamin D was added because the principal investigator had previously observed that supplementation with vitamin D improved insulin sensitivity while reducing C-reactive protein and TG (unpublished data). Related findings have also been reported by other researchers. Fish oil was added primarily because of its proven ability to lower TG levels. Niacin is known to lower TC and LDL while raising HDL. Niacin has also been reported to reduce coronary disease morbidity and mortality.
We still lack firm proof that improvements in CCS that appear to result from the addition of niacin, vitamin D, and fish oil would translate into reductions in myocardial infarction rates or cardiovascular mortality beyond those expected to occur when statins are used as standalone therapy. That said, however, the intriguing findings of the new report suggest that such may well be the case.
These new findings do not tell us which component or components (niacin, fish oil, and/or vitamin D) are key to halting the progression of atherosclerosis. Given that heart disease remains the leading killer of Americans and that improvements in CCS appear likely to reduce cardiovascular disease risk, until we know more, healthcare practitioners may wish to consider administration of this combined-therapy approach in the treatment of patients with risk factors for (or a history of) cardiovascular disease.