Brain More Resistant to Energy Restriction Than Body: A Systematic Review

Abstract

The gluco-lipostatic theory and its modern variants assume that blood glucose and energy stores are controlled in closed-loop feedback processes. The Selfish Brain theory is based on the same assumptions, but additionally postulates that the brain, as an independent energy compartment, self-regulates its energy concentration with the highest priority. In some clinical situations these two theories make opposite predictions. To investigate one of these situations, namely caloric restriction, we formulated a hypothesis which, if confirmed, would match the predictions of the Selfish Brain theory—but not those of the gluco-lipostatic theory. Hypothesis: Calorie restriction causes minor mass (energy) changes in the brain as opposed to major changes in the body. We conducted a systematic review of caloric-restriction studies to test whether or not the evaluated studies confirmed this hypothesis. We identified 3,157 records, screened 2,804 works by title or abstract, and analyzed 232 by full text. According to strict selection criteria (set out in our PROSPERO preregistration, complying with PRISMA guidelines, and the pre-defined hypothesis-decision algorithm), 8 papers provided enough information to decide on the hypothesis: In animals, high-energy phosphates were measured by 31P-nuclear magnetic resonance, and organ and total body weights were measured by scales, while in humans organ sizes were determined by magnetic resonance imaging. All 8 decidable papers confirmed the hypothesis, none spoke against it. The evidence presented here clearly shows that the most accurate predictions are possible with a theory that regards the brain as independently self-regulating and as occupying a primary position in a hierarchically organized energy metabolism.

Proximal Disruption of Brain Energy Supply Raises Systemic Blood Glucose: A Systematic Review

“…In all, the current work confirms the second major prediction of the Selfish-Brain theory that relates to a proximal bottleneck of the cerebral supply chain, cerebral artery occlusion. Its first major prediction relates to a distal supply bottleneck, caloric restriction, and is fulfilled as shown by our previous work, whereas the prediction of the long held gluco-lipostatic theory, which sees the brain as only passively supplied, is violated (Sprengell et al, 2021 ). The crucial point was that caloric restriction elicits smaller changes in mass (energy) in the brain than in the body.…”

“…We included only interventional studies that were standardized laboratory experiments or clinical trials and that examined two groups, an interventional group undergoing cerebral artery occlusion and a non-exposed, sham-operated control group. Since we had included clinical trials in our first systematic review (Sprengell et al, 2021 ), we did the same here for the sake of consistency, but of course did not expect to identify clinical trials, since cerebral artery occlusion in humans is not ethically defensible. We only included studies that measured blood glucose concentration.…”

“…The first one deals with a distal bottleneck, i.e. caloric restriction, and is already published (Sprengell et al, 2021 ); the second one, the current work, deals with a proximal bottleneck, i.e. cerebral artery occlusion.…”

“…caloric restriction ( Figure 2A ). We found that with caloric restriction, the mass (energy) changes in the brain were particularly small (Sprengell et al, 2021 ). Thus, peripheral energetic intervention has little effect on the central nervous system.…”

“…Rival positions include the long-held gluco-lipostatic theory (Kennedy, 1953 ; Mayer, 1953 ) and its modern variants (Chaput and Tremblay, 2009 ; Schwartz et al, 2017 ), which all view the brain as only passively supplied. Our first systematic review showed that caloric restriction causes only minor mass (energy) changes in the brain [of the order of −4%] as opposed to major changes in the body [of about −30%] (Sprengell et al, 2021 ). This finding completely fulfilled the predictions of the Selfish-Brain theory, while those of the gluco-lipostatic theory and its variants were violated.…”