A Diet Rich in Medium-Chain Fatty Acids Improves Systolic Function and Alters the Lipidomic Profile in Patients With Type 2 Diabetes: A Pilot Study.

CONTEXT: Excessive cardiac long-chain fatty acid (LCFA) metabolism/storage causes cardiomyopathy in animal models of type 2 diabetes. Medium-chain fatty acids (MCFAs) are absorbed and oxidized efficiently. Data in animal models of diabetes suggest MCFAs may benefit the heart. OBJECTIVE: Our objective was to test the effects of an MCFA-rich diet vs an LCFA-rich diet on plasma lipids, cardiac steatosis, and function in patients with type 2 diabetes. DESIGN: This was a double-blind, randomized, 2-week matched-feeding study. SETTING: The study included ambulatory patients in the general community. PATIENTS: Sixteen patients, ages 37-65 years, with type 2 diabetes, an ejection fraction greater than 45%, and no other systemic disease were included. INTERVENTION: Fourteen days of a diet rich in MCFAs or LCFAs, containing 38% as fat in total, was undertaken. MAIN OUTCOME MEASURES: Cardiac steatosis and function were the main outcome measures, with lipidomic changes considered a secondary outcome. RESULTS: The relatively load-independent measure of cardiac contractility, S', improved in the MCFA group (P < .05). Weight-adjusted stroke volume and cardiac output decreased in the LCFA group (both P < .05). The MCFA, but not the LCFA, diet decreased several plasma sphingolipids, ceramide, and acylcarnitines implicated in diabetic cardiomyopathy, and changes in several sphingolipids correlated with improved fasting insulins. CONCLUSIONS: Although a diet high in MCFAs does not change cardiac steatosis, our findings suggest that the MCFA-rich diet alters the plasma lipidome and may benefit or at least not harm cardiac function and fasting insulin levels in humans with type 2 diabetes. Larger, long-term studies are needed to further evaluate these effects in less-controlled settings.

Acute Dietary Nitrate Intake Improves Muscle Contractile Function in Patients With Heart Failure: A Double-Blind, Placebo-Controlled, Randomized Trial.

BACKGROUND: Skeletal muscle strength, velocity, and power are markedly reduced in patients with heart failure, which contributes to their impaired exercise capacity and lower quality of life. This muscle dysfunction may be partially because of decreased nitric oxide (NO) bioavailability. We therefore sought to determine whether ingestion of inorganic nitrate (NO3 (-)) would increase NO production and improve muscle function in patients with heart failure because of systolic dysfunction. METHODS AND RESULTS: Using a double-blind, placebo-controlled, randomized crossover design, we determined the effects of dietary NO3 (-) in 9 patients with heart failure. After fasting overnight, subjects drank beetroot juice containing or devoid of 11.2 mmol of NO3 (-). Two hours later, muscle function was assessed using isokinetic dynamometry. Dietary NO3 (-) increased (P<0.05-0.001) breath NO by 35% to 50%. This was accompanied by 9% (P=0.07) and 11% (P<0.05) increases in peak knee extensor power at the 2 highest movement velocities tested (ie, 4.71 and 6.28 rad/s). Maximal power (calculated by fitting peak power data with a parabola) was therefore greater (ie, 4.74±0.41 versus 4.20±0.33 W/kg; P<0.05) after dietary NO3 (-) intake. Calculated maximal velocity of knee extension was also higher after NO3 (-) ingestion (ie, 12.48±0.95 versus 11.11±0.53 rad/s; P<0.05). Blood pressure was unchanged, and no adverse clinical events occurred. CONCLUSIONS: In this pilot study, acute dietary NO3 (-) intake was well tolerated and enhanced NO bioavailability and muscle power in patients with systolic heart failure. Larger-scale studies should be conducted to determine whether the latter translates into an improved quality of life in this population. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01682356.

Effect of acute dietary nitrate intake on maximal knee extensor speed and power in healthy men and women.

Nitric oxide (NO) has been demonstrated to enhance the maximal shortening velocity and maximal power of rodent muscle. Dietary nitrate (NO3(-)) intake has been demonstrated to increase NO bioavailability in humans. We therefore hypothesized that acute dietary NO3(-) intake (in the form of a concentrated beetroot juice (BRJ) supplement) would improve muscle speed and power in humans. To test this hypothesis, healthy men and women (n = 12; age = 22-50 y) were studied using a randomized, double-blind, placebo-controlled crossover design. After an overnight fast, subjects ingested 140 mL of BRJ either containing or devoid of 11.2 mmol of NO3(-). After 2 h, knee extensor contractile function was assessed using a Biodex 4 isokinetic dynamometer. Breath NO levels were also measured periodically using a Niox Mino analyzer as a biomarker of whole-body NO production. No significant changes in breath NO were observed in the placebo trial, whereas breath NO rose by 61% (P < 0.001; effect size = 1.19) after dietary NO3(-) intake. This was accompanied by a 4% (P < 0.01; effect size = 0.74) increase in peak knee extensor power at the highest angular velocity tested (i.e., 6.28 rad/s). Calculated maximal knee extensor power was therefore greater (i.e., 7.90 ± 0.59 vs. 7.44 ± 0.53 W/kg; P < 0.05; effect size = 0.63) after dietary NO3(-) intake, as was the calculated maximal velocity (i.e., 14.5 ± 0.9 vs. 13.1 ± 0.8 rad/s; P < 0.05; effect size = 0.67). No differences in muscle function were observed during 50 consecutive knee extensions performed at 3.14 rad/s. We conclude that acute dietary NO3(-) intake increases whole-body NO production and muscle speed and power in healthy men and women.