The following hypothesis is suggested from classic studies of starvation done in chronically fasted obese individuals [27,28]. The brain's metabolism requires 100 grams of glucose per day. In the early phase of starvation, glycogen stores are rapidly reduced, so the requirement for glucose, is met by gluconeogenesis. Approximately 15–20 grams are available from glycerol production due to lipolysis, but fatty acid oxidation generally cannot be used to produce glucose. Therefore, protein breakdown must supply the rest of substrate for conversion to glucose in the early phases of starvation. By 6 weeks of starvation, ketone bodies plus glycerol can replace 85% of the brain's metabolic needs, the remainder still arising from gluconeogenesis due to protein. It should be mentioned that, since the fundamental role of ketones is to spare protein, it might be expected that the reliance on protein would actually decrease with time, perhaps relating to the anecdotal observation of "hitting the wall" on weight loss diets.
Very low carbohydrate diets, in their early phases, also must supply substantial glucose to the brain from gluconeogenesis. For example, the early phase of the popular Atkins or Protein Power diet restricts dieters to about 20–30 grams of carbohydrate per day, leaving 60–65 grams to be made up from protein-originated gluconeogenesis. One hundred grams of an "average" protein can supply about 57 grams of glucose so 110 grams protein would be needed to provide 60–65 grams glucose. Increased gluconeogenesis has been directly confirmed using tracer studies on day 11 of a very low carbohydrate diet (approx 8 grams/day) [29]. If indeed, 110 grams of endogenous protein is broken down for gluconeogenesis and re-synthesized, the energy cost, at 4–5 kcal/gram could amount to as much as 400–600 kcal/day. This is a sizable metabolic advantage. Of course, the source of protein for gluconeogenesis may be dietary rather than endogenous. Whereas endogenous protein breakdown is likely to evoke energetically costly re-synthesis in an organism in homeostasis, dietary protein may conserve energy. The source of protein for the observed gluconeogenesis [29] remains an open question, but there is no a priori reason to exclude endogenous rather than dietary sources. This is therefore a hypothesis that would need to be tested. The extent to which the protein for gluconeogenesis is supplied by endogenous protein would explain very high-energy costs. It should be noted, however, that even if limited to breakdown of dietary protein sources, there would be some energy cost associated with gluconeogenesis.
สมมติฐานต่อไปนี้เป็นการแนะนำจากศึกษาคลาสสิกของความอดอยากในคนอ้วนเชื่อโรคเรื้อรัง [27,28] เผาผลาญของสมองต้องการน้ำตาลกลูโคสวันละ 100 กรัม ในระยะเริ่มต้นของความอดอยาก เก็บไกลโคเจนได้อย่างรวดเร็วลดลง เพื่อตอบสนองความต้องการน้ำตาลกลูโคส การสร้างกลูโคส ประมาณ 15 – 20 กรัมได้กลีเซอรผลิตเนื่องจากการผลิตระหว่างประเทศ แต่เกิดออกซิเดชันของกรดไขมันโดยทั่วไปไม่สามารถใช้ในการผลิตกลูโคส ดังนั้น แบ่งโปรตีนต้องใส่ส่วนเหลือของพื้นผิวสำหรับการแปลงให้กลูโคสในระยะแรก ๆ ของความอดอยาก สัปดาห์ที่ 6 ของความอดอยาก คีโตนบอดีส์และกลีเซอรสามารถแทน 85% ต้องการเผาผลาญของสมอง ส่วนเหลือยังคง เกิดจากการสร้างกลูโคสจากโปรตีน มันควรจะกล่าวว่า เนื่องจากบทบาทพื้นฐานของคีโตนจะอะไหล่โปรตีน จึงคาดหมายได้ว่า พึ่งโปรตีนจะจริงลดเวลา อาจจะเกี่ยวข้องกับการสังเกตเล็ก ๆ ของ "ตีผนัง" ในอาหารลดน้ำหนักVery low carbohydrate diets, in their early phases, also must supply substantial glucose to the brain from gluconeogenesis. For example, the early phase of the popular Atkins or Protein Power diet restricts dieters to about 20–30 grams of carbohydrate per day, leaving 60–65 grams to be made up from protein-originated gluconeogenesis. One hundred grams of an "average" protein can supply about 57 grams of glucose so 110 grams protein would be needed to provide 60–65 grams glucose. Increased gluconeogenesis has been directly confirmed using tracer studies on day 11 of a very low carbohydrate diet (approx 8 grams/day) [29]. If indeed, 110 grams of endogenous protein is broken down for gluconeogenesis and re-synthesized, the energy cost, at 4–5 kcal/gram could amount to as much as 400–600 kcal/day. This is a sizable metabolic advantage. Of course, the source of protein for gluconeogenesis may be dietary rather than endogenous. Whereas endogenous protein breakdown is likely to evoke energetically costly re-synthesis in an organism in homeostasis, dietary protein may conserve energy. The source of protein for the observed gluconeogenesis [29] remains an open question, but there is no a priori reason to exclude endogenous rather than dietary sources. This is therefore a hypothesis that would need to be tested. The extent to which the protein for gluconeogenesis is supplied by endogenous protein would explain very high-energy costs. It should be noted, however, that even if limited to breakdown of dietary protein sources, there would be some energy cost associated with gluconeogenesis.
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