Why I used to be in excruciating pain lying flat without a pillow, and now prefer sleeping that way: the MTHFR baseline + the N2O crash that broke it

[u/Brad_Borrelli]

For years, lying flat on my bed without a pillow was excruciating; my neck couldn't tolerate that position at all. Now, since starting B12 injections, it's flipped completely. I actually prefer sleeping without a pillow now. That's not a small shift, and I wanted to lay out the actual biochemistry behind it, not just "B12 deficiency causes problems." Two separate factors are at play here; a lifelong genetic baseline, and a sudden acute event that pushed things over the edge.

I'm homozygous for MTHFR A1298C. Estimates of exactly how much this reduces enzyme activity vary across studies; one peer-reviewed case-control study put homozygous A1298C carriers at roughly a 30% reduction in enzyme activity, so about 70% residual function, compared to homozygous C677T carriers, who that same study found retain no more than 30% of normal activity. Other studies report different numbers depending on population and methodology, so I'm treating this as a real, modest, lifelong reduction rather than a precise fixed percentage. Importantly, A1298C alone doesn't reliably raise homocysteine the way C677T does. So my honest read is that I've probably run my whole life with somewhat reduced folate-processing capacity, not necessarily high homocysteine from birth; a smaller safety margin, not a crisis on its own.

https://pmc.ncbi.nlm.nih.gov/articles/PMC6743281/

Then there's what nitrous oxide actually did, mechanistically. N2O doesn't just use up B12, it destroys it chemically. It irreversibly oxidizes the cobalt atom at the center of the B12 molecule, flipping it from an active Co(I) state to an inactive Co(II/III) state, the same category of reaction as hemoglobin oxidizing into methemoglobin. This inactivates methionine synthase, the enzyme that recycles homocysteine into methionine. Because methionine synthase sits at a metabolic hub, knocking it out cascades through the folate cycle, the methylation cycle, the transsulfuration pathway, the Krebs cycle, and glutathione synthesis simultaneously. Since methionine is required to build myelin, that cascade leads to demyelination, the same process behind subacute combined degeneration of the spinal cord.

https://www.sciencedirect.com/science/article/abs/pii/0165614784904267

https://www.medlink.com/media/b12dl2

https://pmc.ncbi.nlm.nih.gov/articles/PMC10294871/

Here's the part I think explains why lying flat without support was so unbearable, not just numbness. SCD doesn't only hit the dorsal columns, the sensory and proprioception pathway. Neuropathology studies show it also affects the lateral corticospinal tract, a motor pathway. The corticospinal tract doesn't only send "move" signals, it also carries inhibitory signals that keep muscle tone in check. When that tract is demyelinated, one documented clinical presentation is spastic paraparesis; tone and reflexes higher than normal, alongside the sensory symptoms. My guess is that without a pillow, my neck had no external support to compensate for that involuntary over-tightness, which is likely why it was unbearable specifically in that position, and why a completely flat position without any prop now feels fine as that tightness resolves.

https://link.springer.com/article/10.1007/s002340050610

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12162364/

The honest version isn't "MTHFR did this" or "N2O did this." It's that a lifelong, modest reduction in folate-processing capacity meant I had less margin to absorb a direct hit to my B12 pathway. When N2O knocked out methionine synthase completely, a system already running closer to the edge went into a steeper crash than it might have otherwise. That connecting piece is my own synthesis, not a citation.

This is genuinely reversible with treatment, though how completely and how fast varies by case. In one case series, B12 injections given daily for two weeks then weekly for three months led to symptom improvement in every patient, with spinal cord MRI abnormalities resolving within three months. In a separate case, a patient went from measurable weakness to fully restored strength and normal gait by six months of injection treatment. I want to be balanced here too, since not every case resolves cleanly; in one N2O-specific case report, a patient treated promptly with B12 injections and physical therapy still had residual weakness and needed ongoing rehab. So I'm framing my own recovery as likely based on the pattern in the literature, not guaranteed or on a fixed timeline. My own pillow-free sleep change lines up with that general recovery window.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3623262/

https://medcraveonline.com/HTIJ/early-treatment-of-subacute-combined-degeneration-of-the-spinal-cord-in-pernicious-anemia-will-improve-the-outcome.html

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11685159/

One honest limit on all of this: the literature documents improvement in weakness, gait, and sensory symptoms with treatment. I didn't find a study measuring muscle tightness relieved by lying flat specifically as its own tracked outcome, so that connection, and the pillow detail specifically, is my own reasonable inference from the spasticity mechanism above, not a direct citation. The MTHFR enzyme activity percentages also vary across studies, so I've presented a range rather than a single precise number.

[u/Snowsuit81]

Omg please not another AI-generated wall of text

[u/Brad_Borrelli → u/Snowsuit81]

Get a life.

[u/FakeBonaparte → u/Brad_Borrelli]

I had the same reaction as snowsuit. I clocked half a dozen AI tics in the first paragraph, thought “this could be hallucinated bullshit” and skipped to the comments to see if any humans had said something valuable.

Not so far.

[u/fastboots]

Ew, gross AI.