Effect of baseline plasma fatty acids on eicosapentaenoic acid levels in individuals supplemented with alpha-linolenic acid.

We previously reported a >50% increase in mean plasma eicosapentaenoic acid levels in a general medicine clinic population after supplementation with alpha-linolenic acid. In the current analysis, we evaluate the variability of changes in eicosapentaenoic acid levels among individuals supplemented with alpha-linolenic acid and evaluated the impact of baseline plasma fatty acids levels on changes in eicosapentaenoic acid levels in these individuals. Changes in eicosapentaenoic acid levels among individuals supplemented with alpha-linolenic acid ranged from a 55% decrease to a 967% increase. Baseline plasma fatty acids had no statistically significant effect on changes in eicosapentaenoic levels acid after alpha-linolenic acid supplementation. Changes in eicosapentaenoic acid levels varied considerably in a general internal medicine clinic population supplemented with alpha-linolenic acid. Factors that may impact changes in plasma eicosapentaenoic acid levels after alpha-linolenic acid supplementation warrant further study.

Managing dyslipidemia in chronic kidney disease.

The incidence of chronic kidney disease (CKD) in the U.S. continues to increase, and now over 10% of the U.S. population has some form of CKD. Although some patients with CKD will ultimately develop renal failure, most patients with CKD will die of cardiovascular disease before dialysis becomes necessary. Patients with CKD have major proatherogenic lipid abnormalities that are treatable with readily available therapies. The severe derangements seen in lipoprotein metabolism in patients with CKD typically results in high triglycerides and low high-density lipoprotein (HDL) cholesterol. Because of the prevalence of triglyceride disorders in patients with CKD, after treating patients to a low-density lipoprotein goal, non-HDL should be calculated and used as the secondary goal of treatment. A review of the evidence from subgroup analysis of several landmark lipid-lowering trials supports treating dyslipidemia in mild to moderate CKD patients with HMG-CoA reductase inhibitors. The evidence to support treating dyslipidemia in hemodialysis patients, however, has been mixed, with several outcome trials pending. Patients with CKD frequently have mixed dyslipidemia and often require treatment with multiple lipid-lowering drugs. Although statins are the cornerstone of therapy for most patients with CKD, differences in their pharmacokinetic properties give some statins a safety advantage in patients with advanced CKD. Although most other lipid-lowering agents can be used safely with statins in combination therapy in patients with CKD, the fibrates are renally metabolized and require both adjustments in dose and very careful monitoring due to the increased risk of rhabdomyolysis. After reviewing the safety and dose alterations required in managing dyslipidemia in patients with CKD, a practical treatment algorithm is proposed.

Flaxseed oil supplementation does not affect plasma lipoprotein concentration or particle size in human subjects.

alpha-Linolenic acid (ALA) is a major dietary (n-3) fatty acid. Some clinical trials with ALA supplementation have shown reduced cardiovascular risk; however the specific cardioprotective mechanism is not known. We studied the effects of daily supplementation with ALA derived from flaxseed oil on concentrations of plasma LDL cholesterol, HDL cholesterol, intermediate density lipoprotein cholesterol, and lipid particle sizes. In a randomized double-blind trial, 56 participants were given 3 g/d of ALA from flaxseed oil in capsules (n = 31) or olive oil containing placebo capsules (n = 25) for 26 wk. Changes in plasma HDL cholesterol, LDL cholesterol, and triglyceride concentrations did not differ between the 2 groups at 26 wk. The adjusted plasma total cholesterol concentration at 26 wk was 0.45 mmol/L higher in the flaxseed oil group (5.43 +/- 0.03 mmol/L) compared with the olive oil group (5.17 +/- 0.07 mmol/L) (P = 0.026). ALA did not affect LDL, HDL, or IDL particle size; however, the concentrations of the large, less atherogenic LDL1 (P = 0.058) and LDL2 (P = 0.083) subfractions tended to be greater in the ALA group. In conclusion, ALA does not decrease CVD risk by altering lipoprotein particle size or plasma lipoprotein concentrations.

Flaxseed oil increases the plasma concentrations of cardioprotective (n-3) fatty acids in humans.

Alpha-linolenic acid (ALA) is a major dietary (n-3) fatty acid. ALA is converted to longer-chain (n-3) PUFA, such as eicosapentaenoic acid (EPA) and possibly docosahexaenoic acid (DHA). EPA and DHA are fish-based (n-3) fatty acids that have proven cardioprotective properties. We studied the effect of daily supplementation with 3 g of ALA on the plasma concentration of long-chain (n-3) fatty acids in a predominantly African-American population with chronic illness. In a randomized, double-blind trial, 56 participants were given 3 g ALA/d from flaxseed oil capsules (n = 31) or olive oil placebo capsules (n = 25). Plasma EPA levels at 12 wk in the flaxseed oil group increased by 60%, from 24.09 +/- 16.71 to 38.56 +/- 28.92 micromol/L (P = 0.004), whereas no change occurred in the olive oil group. Plasma docosapentaenoic acid (DPA) levels in the flaxseed oil group increased by 25% from 19.94 +/- 9.22 to 27.03 +/- 17.17 micromol/L (P = 0.03) with no change in the olive oil group. Plasma DHA levels did not change in either group. This study demonstrates the efficacy of the conversion of ALA to EPA and DPA in a minority population with chronic disease. ALA may be an alternative to fish oil; however, additional clinical trials with ALA are warranted.

Usefulness of omega-3 fatty acids and the prevention of coronary heart disease.

Clinical trial evidence exists that supports a role for the omega-3 polyunsaturated fatty acids in coronary heart disease prevention. However, the results from these clinical trials have varied and were conducted in diverse population groups using several different types of omega-3 polyunsaturated fatty acids, including eicosapentaenoic acid, docosahexaenoic acid, and alpha-linolenic acid (ALA). Thus, we systematically reviewed previously published reports assessing the different types of omega-3 polyunsaturated fatty acid interventions and cardiovascular outcomes. Fourteen randomized clinical trials were included in the review. Six trials were included with fish oil, with 1 large trial (10,000 patients) dominating the analysis. In aggregate, the fish oil trials demonstrated a reduction in total mortality and sudden death without a clinically significant reduction in nonfatal myocardial infarction. The 6 trials with ALA supplements or an ALA-enriched diet were of poorer design than the fish oil trials and had limited power. Many of the trials with ALA involved other changes in dietary components. In aggregate, the ALA trials demonstrated possible benefits in reducing sudden death and nonfatal myocardial infarction, but with wider confidence intervals than in the fish oil trials. In conclusion, the evidence suggests a role for fish oil (eicosapentaenoic acid, docosahexaenoic acid) or fish in secondary prevention because recent clinical trial data have demonstrated a significant reduction in total mortality, coronary heart disease death, and sudden death. The data on ALA have been limited by studies of smaller sample size and limited quality.

Beyond the Mediterranean diet: the role of omega-3 Fatty acids in the prevention of coronary heart disease.

Evidence from epidemiologic and clinical secondary prevention trials suggest that the omega-3 polyunsaturated fatty acids (n-3 PUFAs) may have a significant role in the prevention of coronary heart disease. Dietary sources of n-3 PUFAs include fish oils, rich in eicosapentaenoic acid and docosahexaenoic acid, along with plants rich in a-linolenic acid. Randomized secondary prevention clinical trials with fish oils (eicosapentaenoic acid, docosahexaenoic acid) and a-linolenic acid have demonstrated reductions in risk that compare favorably to those seen in landmark secondary prevention trials with lipid-lowering drugs. Several mechanisms explaining the cardioprotective effect of the n-3 PUFA have been suggested including antiarrhythmic and antithrombotic roles. Although official US guidelines for the dietary intake of n-3 PUFA are not available, several international guidelines have been published. Fish is an important source of the n-3 PUFA in the US diet; however, vegetable sources including grains and oils offer an alternative source for those who are unable to regularly consume fish.