Schoeller, Dale A.

Abstract Medical nutrition therapy for long‐chain fatty acid oxidation disorders (LC‐FAODs) currently emphasizes fasting avoidance, restricted dietary long‐chain fatty acid intake, supplementation with medium chain triglycerides, and increased carbohydrate intake. We hypothesize that increasing dietary protein intake relative to carbohydrate intake would preserve metabolic control yet induce physical benefits including reduced hepatic lipogenesis. Therefore, we compared two dietary approaches with similar fat intake but different carbohydrate to protein ratios in participants diagnosed with LC‐FAODs. Thirteen participants were enrolled and randomized into either a high‐protein (PRO) or a high‐carbohydrate (CHO) diet for 4 months. Baseline and 4‐month assessments included body composition, ectopic lipid deposition, and resting energy expenditure. End of study assessments also included total energy expenditure, metabolic responses to oral feedings, and whole‐body fatty acid oxidation capacity. At the end of the dietary intervention, both groups had similar energy expenditure, fat and glucose oxidation rates, and glucolipid responses to mixed meal and oral glucose loads. Neither dietary group experienced worsening symptoms related to their LC‐FAOD. Compared to the CHO group, the PRO group exhibited increased blood levels of short‐chain acylcarnitines, reduced intrahepatic lipid content, and maintained lean body mass while the CHO group lost lean mass. In patients with LC‐FAODs, increasing protein intake maintained metabolic control, reduced liver fat without risk of metabolic decompensation, and helped preserve lean body mass. We propose that a modest increase in dietary protein along with fasting avoidance and fat restriction may improve body composition and energy expenditure in patients with LC‐FAODs.

Objective Little is known about long‐term metabolic (energy expenditure) adaptation after bariatric surgery. Methods Resting metabolic rate under basal conditions (RMR), total daily energy expenditure (TDEE), and body composition were measured in 25 participants in the Longitudinal Assessment of Bariatric Surgery‐2. Results Six months after surgery, BMI (±SD) decreased (47 ± 6 kg/m 2 to 37 ± 5 kg/m 2 ), body fat went from 48% ± 6% to 40% ± 6% fat, and fat‐free mass went from 67 ± 9 kg to 60 ± 9 kg. In absolute terms, RMR and TDEE both decreased significantly (1,730 ± 278 kcal/d vs. 1,430 ± 200 kcal/d and 2,879 ± 544 kcal/d vs. 2,369 ± 304 kcal/d), and the achieved energy balance was −1,293 ± 355 kcal/d. Sixteen of these participants underwent repeated measures at ∼24 months; TDEE decreased 6 months postoperatively (2,957 ± 540 kcal/d to 2,423 ± 324 kcal/d; P = 0.0003), but at ∼24 months, TDEE (2,602 ± 471 kcal/d) was not significantly different compared with month 6. The average negative energy balance from baseline to month 24 was −379 ± 131 kcal/d. Conclusions RMR and TDEE fall precipitously in the first 6 months after bariatric surgery, but these adaptive changes were no longer significant after 2 years.

The development of insulin resistance has been associated with impaired mitochondrial fatty acid oxidation (FAO), but the exact relationship between FAO capacity and glucose metabolism continues to be debated. To address this controversy, patients with long-chain 3-hydroxy acyl-CoA dehydrogenase (LCHAD) deficiency underwent an oral glucose tolerance test (OGTT) and measurement of energy expenditure, body composition, and plasma metabolites. Compared with controls, patients with LCHAD deficiency had a trend toward higher total body fat and extramyocellular lipid deposition but similar levels of intramyocelluar and intrahepatic lipids. Resting energy expenditure was similar between the groups, but respiratory quotient was higher and total energy expenditure was lower in LCHAD-deficient patients compared with controls. High-molecular-weight (HMW) adiponectin levels were lower and plasma long-chain acylcarnitines were higher among LCHAD-deficient patients. Fasting and post-OGTT levels of glucose, insulin, and ghrelin, along with estimates of insulin sensitivity, were the same between the groups. Despite decreased capacity for FAO, lower total energy expenditure and plasma HMW adiponectin, and increased plasma acylcarnitines, LCHAD-deficient patients exhibited normal glucose tolerance. These data suggest that inhibition of the FAO pathway in humans is not sufficient to induce insulin resistance.