Well ok it’s fruit flies but still.
Interesting paper, thanks! With luck I’ll liver forever or at least longer than a fruit fly. I’ve been mixing my salt with mineral citrates of magnesium, potassium, sodium, calcium and a little bit of zinc and maganese. When I shifted to eating higher protein and cutting back on fruit and veg my urine got too acidic and I leaked a little protein. I also had a dip in bone density. Swapping in the mineral citrates for much of my salt fixed those issues and also surprisingly mostly stopped my episodes of puffy feet and ankles for which over several years I’ve found many things would make a little better or worse but nothing else has brought this much improvement. Eating higher protein also tanked my ketones despite a significant drop in my daily carbs. The citrates also seem to have mildly boosted my ketones but they still aren’t as high as when I ate moderate protein.
Ditto - for finding this! Thanks.
If possible, I’d prefer to get citrate from food rather than supplements, although I’m not against citrate salts. Anyway, I found this:
… it’s recommended that you consume at least 3.5 grams of potassium citrate and other potassium salts each day in order to keep your body healthy.
… Animal sources of potassium citrate include fish, chicken, and beef.
@RightNOW From the paper you linked. Curiously, the links included in this discussion
all link to the paper, not the supposed citation. Don’t know what that’s about. Figured it out! The links work only when selected within the article itself: they display in a sidebar to to the right of the main text. Within that sidebar are links that work to the various cited papers.
Our genetic experiments in flies reveal an important role for ketogenesis in mediating citrate-induced lifespan extension. Dietary βOHB administration in our fly experimental model consistently resulted in an increased lifespan, similar to what was observed in C . elegans (Edwards et al., 2014). Another striking finding involving ketone body-associated longevity regulation is the lifespan-extending effect of ketogenic diets demonstrated in recent mouse studies (Newman et al., 2017; Roberts et al., 2017). Our results in mice detail the health benefits of βOHB supplementation, similar to findings of previous reports, including body weight loss, increased energy expenditure, and improved glucose hemostasis, but with a significantly reduced food intake (Kashiwaya et al., 2010; Srivastava et al., 2012). Although the inhibitory effect of βOHB on food intake is well-documented, the underlying cellular and molecular mechanisms are not fully understood. A previous study suggests that local production of βOHB by astrocytes is essential for βOHB-induced appetite suppression, through its action on fatty acid-sensing neurons in the ventromedial hypothalamus (Le Foll et al., 2014). This raised the possibility that βOHB as a dietary supplement may act directly on neurons to suppress feeding, while supplementary citrate may require further metabolic steps to initiate ketogenesis. This discrepancy might explain why dietary supplementation of citrate did not induce an obvious feeding suppression such as that seen in mice receiving supplementary βOHB. Lower body weight in βOHB-treated mice also contributes to improved motor learning and motor control, which are commonly seen in animals under DR (Ingram et al., 1987).
In addition to their role as an alternative energy resource during carbohydrate deprivation, some evidence suggests that ketone bodies may act as signaling molecules. βOHB has been shown to bind and inhibit the activity of class I histone deacetylases (Riggs et al., 1977; Shimazu et al., 2013), possibly accounting for the observation of histone hyperacetylation in cells treated with βOHB both in vitro and in vivo , and βOHB treatment also leads to transcriptional changes in genes associated with cell survival and oxidative stress responses (Shimazu et al., 2013). Two recent studies invoked a similar mechanism in showing that βOHB-induced expression of brain-derived neurotrophic factor (BDNF) in cortical and hippocampal neurons, both in cell culture and in mice (Marosi et al., 2016; Sleiman et al., 2016). Further, βOHB-induced BDNF expression could play an important role in regulation of the synaptic plasticity that contributes to increased spine formation and improved memory performance observed in this study. Our recent work and a previous report point out that deletion of the mammalian citrate transporter Indy in mice can induce improved metabolic health, memory performance, and increased ketogenesis (Birkenfeld et al., 2011; Fan et al., 2021). These observations further support our hypothesis of a biphasic effect of citrate in the regulation of physiology. Interestingly, both citrate supplementation and mammalian Indy knockout mice display improved performance in memory tests, but not in the other tests of cognitive function examined in this study. Higher expression levels of mammalian Indy in the cerebral cortex and hippocampus could be a possible explanation for this discrepancy, though the expression pattern of the other citrate transporters in the brain has not been fully investigated (Fan et al., 2021). Further experiments will be helpful in dissecting the interaction of citrate supplementation and the various citrate transporters in cognitive regulation.
I’m no fruit fly…
Nor rodent, nor nematode… yet studies using these animals because of their relatively short lifespans have enabled scientists to learn a lot about human metabolism, health and disease. Sure, you have to realize that studies of these and other animals may or may not be directly applicable to humans - and you have to look carefully at the study parameters - but don’t dismiss studies as irrelevant just because they are/were not controlled, double-blind, crossover studies of human subjects. I think we can learn more from a good nutritional study of drosophila than a nutritional epidemiological study of humans that uses a ‘what did you eat and how much’ questionaire.