Prenatal molecular diagnosis of pyruvate dehydrogenase complex deficiency enables rapid initiation of ketogenic diet.

Pyruvate dehydrogenase complex deficiency (PDCD) is a mitochondrial disorder of carbohydrate oxidation characterized by lactic acidosis and central nervous system involvement. Knowledge of the affected metabolic pathways and clinical observations suggest that early initiation of the ketogenic diet may ameliorate the metabolic and neurologic course of the disease. We present a case in which first trimester ultrasound identified structural brain abnormalities prompting a prenatal molecular diagnosis of PDCD. Ketogenic diet, thiamine, and N-acetylcysteine were initiated in the perinatal period with good response, including sustained developmental progress. This case highlights the importance of a robust neurometabolic differential diagnosis for prenatally diagnosed structural anomalies and the use of prenatal molecular testing to facilitate rapid, genetically tailored intervention.

Quantifying the imprecision of energy intake of humans to compensate for imposed energetic errors: A challenge to the physiological control of human food intake.

To assess the precision of the biological control of energy intake we performed a systematic review of studies that measured acute changes in human food intake in response to energetic errors. The imposed errors were grouped into the following categories of studies: alternate day fasting, changes in diet composition, exercise, meal skipping, overfeeding, energy substitutes, underfeeding and changes in portion size. Seven hundred thirty-nine studies published between 1980 and 2017 were identified from which the data from 592 groups from 200 studies were extracted and subjected to analysis consisting of a total of 13,203 participants. For each category of imposing an energetic error, an Energetic Error was calculated as (Observed Mean Energy Intake - Expected Mean Energy Intake)/Expected Mean Energy Intake. In no category of studies was the Energetic Error equal to zero. In studies where participants were expected to increase energy intake, the increase was not sufficient to overcome the deficit. Similarly, in studies where a reduction in energy intake was expected, the reduction was insufficient to restore energy balance to zero. The average energetic error resulting from imposed energetic challenges is about twenty-four percent, a value sufficiently large to account for the increase in body weight observed in the U.S. population over the past 50 years.

Lack of negative autocorrelations of daily food intake on successive days challenges the concept of the regulation of body weight in humans.

According to most theories, the amount of food consumed on one day should be negatively related to intake on subsequent days. Several studies have observed such a negative correlation between the amount consumed on one day and the amount consumed two to four days later. The present study attempted to replicate this observation by re-examining data from a previous study where all food ingested over a 30-day observation period was measured. Nine male and seven female participants received a vegan diet prepared, dispensed, and measured in a metabolic unit. Autocorrelations were performed on total food intake consume on one day and that consumed one to five days later. A significant positive correlation was detected between the weight of food eaten on one day and on the amount consumed on the following day (r = 0.29, 95% CI [0.37, 0.20]). No correlation was found between weights of food consumed on one day and up to twelve days later (r = 0.09, 95% CI [0.24, -0.06]), (r = 0.11, 95% CI [0.26, -0.0.26]) (r = 0.02, 95% CI [0.15, -0.7]) (r = -0.08, 95% CI [0.11, -0.09]). The same positive correlation with the previous day's intake was observed at the succeeding breakfast but not at either lunch or dinner. However, the participants underestimated their daily energy need resulting in a small, but statistically significant weight loss. Daily food intake increased slightly (13 g/day), but significantly, across the 30-day period. An analysis of the previous studies revealed that the negative correlations observed by others was caused by a statistical artifact resulting from normalizing data before testing for the correlations. These results, when combined with the published literature, indicate that there is little evidence that humans precisely compensate for the previous day's intake by altering the amount consumed on subsequent days. Moreover, the small but persistent increase in food intake suggests that physiological mechanisms that affect food intake operate more subtly and over much longer periods of time than the meal or even total daily intake.

The Rise and Fall of Physiological Theories of the Control of Human Eating Behavior.

Kuhns was the first to suggest that theories in science do not develop in small increments but rather in major leaps to paradigms that examine the same question through very different perspectives. Theories on the mechanism responsible for control of human food intake fall into Kuhn's description. This article describes how the two major theories of the control of food intake in humans, the Glucostatic Theory, and the Lipostatic Theory, showed initial promise as explanations, but later deteriorated with the slow accumulation experimental data. The locus of theories considered eating behavior as a part of physiological system that regulates the storage of energy on the body. We challenge this fundamental belief with data which suggests that we must be ready to accept a major change in the way we think about eating behavior if we are ever to decrease the prevalence of obesity.