The paper is a super fascinating read, and lines up with several key features I've noticed in both of my professionally diagnosed autistic children (good luck getting access to a competent diagnostician who understands how the ASD criteria manifest in passing adults). It's really enlightening to see the association between Xanthine, one of the end-stage products of eATP metabolization, and the anxiety that is so prevalent within my own family.
From the Discussion[1] section of the paper:
> These self-calming connections in metabolism failed to develop in ASD. The natural consequence of the loss of these metabolic safeguards to overexcitation is for children with ASD to seek sameness to avoid the anxiety produced by change91, and to be more sensitive to environmental changes across many sensory domains.
And a bit further on:
> In the current study, xanthine was the purine that gained the most stimulatory (+r) correlations in 5-year-olds with ASD. Xanthine is one of the end-products of eATP metabolism97. Xanthine is known to trigger a cascade of events that leads to mitochondrial network fragmentation, reactive oxygen species and reactive nitrogen species (ROS and RNS), eicosanoid (e.g., leukotriene, HETE, and prostaglandin) signaling, immune activation, anxiety-associated behaviors, and consolidates long-term aversive memories that make the animal hypersensitive to future environmental changes that warn of environmental danger, cause fear, and trigger anxiety in mice, and is elevated in the blood of adults with anxiety disorders98. Anxiety is a common but under-recognized problem in autism99.
Another really important observation:
> A major result of this research was that the developmental differences observed in ASD were not the result of an increase or decrease of one causal metabolite, or an isolated change in the gut-brain axis, or neuroendocrine, autonomic, cytokine, or immunologic circuits. Instead, it was the interconnectedness and developmental state of the metabolic network that underlies all these systems that was fundamentally changed.
In the last year, the All Brains Belong VT organization has been working on a collection of information they call "All The Things" [2], which lines up with the paper's observation that there is an underlying metabolic network at play. As a side note, All Brains Belong VT is a fantastic organization that focuses heavily on validation and support in a healthcare industry which often feels incredibly invalidating for individuals who have been reporting symptoms across a wide variety of siloed physician specialties.
It's less a matter of making fructose into a good sugar, and more a matter of reducing the bioavailability of it. When you eat a piece of fruit, your body has to break it down in order to get at the fructose, and that takes enough time that you're now competing with your gut bacteria for access to that fructose. When you drink it in a soda, it's much easier to process and you have a significantly higher chance of absorbing it at soon at it enters your small intestine.
This reminds me of some other fascinating projects: The Clock[1] and The Tower[2]. Several years ago I thought about building a dead-bug style Christmas tree for a decoration competition. Projects like these continually remind me that when we're not optimizing for space, you really can make something functional _and_ beautiful.
The container was last watered twelve years after it was planted. Twelve years is plenty of time for most plants (especially something many people would consider a weed) to reach that size. At this point it's simply in maintenance mode - similar to a bonsai which never requires trimming.
From the Discussion[1] section of the paper:
> These self-calming connections in metabolism failed to develop in ASD. The natural consequence of the loss of these metabolic safeguards to overexcitation is for children with ASD to seek sameness to avoid the anxiety produced by change91, and to be more sensitive to environmental changes across many sensory domains.
And a bit further on:
> In the current study, xanthine was the purine that gained the most stimulatory (+r) correlations in 5-year-olds with ASD. Xanthine is one of the end-products of eATP metabolism97. Xanthine is known to trigger a cascade of events that leads to mitochondrial network fragmentation, reactive oxygen species and reactive nitrogen species (ROS and RNS), eicosanoid (e.g., leukotriene, HETE, and prostaglandin) signaling, immune activation, anxiety-associated behaviors, and consolidates long-term aversive memories that make the animal hypersensitive to future environmental changes that warn of environmental danger, cause fear, and trigger anxiety in mice, and is elevated in the blood of adults with anxiety disorders98. Anxiety is a common but under-recognized problem in autism99.
Another really important observation:
> A major result of this research was that the developmental differences observed in ASD were not the result of an increase or decrease of one causal metabolite, or an isolated change in the gut-brain axis, or neuroendocrine, autonomic, cytokine, or immunologic circuits. Instead, it was the interconnectedness and developmental state of the metabolic network that underlies all these systems that was fundamentally changed.
In the last year, the All Brains Belong VT organization has been working on a collection of information they call "All The Things" [2], which lines up with the paper's observation that there is an underlying metabolic network at play. As a side note, All Brains Belong VT is a fantastic organization that focuses heavily on validation and support in a healthcare industry which often feels incredibly invalidating for individuals who have been reporting symptoms across a wide variety of siloed physician specialties.
[1]: https://www.nature.com/articles/s42003-024-06102-y#Sec25
[2]: https://allbrainsbelong.org/all-the-things/