That's what I assumed from other readings. Why, then, can I only find studies administering B12 near the time of the surgery? Those studies still found protective effects on homocysteine elevation, but that may be mostly due to the coadministered B9.

This means B12 should be taken either well before NO, or sometime after. Given the short half life of NO, it should be fine to take B12 orally immediately after a final NO dose; the B12 will be absorbed shorty after the NO is eliminated.

Note that, though folate and B12 were given IV before and after surgery, it did not have an immediate effect. The NO induced rise in homocysteine was not blunted by the end of surgery. However, postoperative homocysteine was lowered to below baseline on all 3 measurement days. The NO induced rise in homocysteine lasted 2 days postoperatively.

Unsurprisingly, this suggests a lag time between B vitamin administration and homocysteine drop. Thus, what I'd really like to see is a study administering B vitamins 1 day prior to NO use.

This suggests those taking NO should supplement with both B9 and B12. It is likely that the effects on B9 are more acute, while B12 deficiency probably only becomes an issue with chronic abuse or in those with borderline B12 status to begin with.

This demonstrates that tolerance is possible. However, exposure in humans lasts only several minutes at a time. Let's assume 3 exposures per day lasting 10 minutes each (i.e. 30 minutes total). It would take 68 days to reach 34 hours of exposure. Alternatively, that's a ratio of 1 to 47 exposure to non-exposure. It's unclear whether that would be sufficient for tolerance.

In the 50% exposure group, convulsion score was effectively zero by hour 6 (from full text). This does not mean that withdrawal symptoms were gone. However, it does imply that recovery is rapid. It seems plausible that 20 hours between doses is sufficient to reach baseline, rendering tolerance in humans extremely unlikely. I will need to compare to alcohol withdrawal to confirm.

Edit: Alcohol withdrawal in mice can be induced with 72 hours of alcohol exposure. That implies it is similar to NO. In humans, "the shakes" appear to last 1 or two weeks. In mice, convulsions appear to be half gone in 25 hours, suggesting that they last a few days. Thus, it appears that NO withdrawal is possibly an order of magnitude shorter than alcohol withdrawal.

In conclusion, NO used in a normal fashion is unlikely to be harmful (except for risk of inducing B12 deficiency). Even if it is harmful, the short half life means that it will be apparent very quickly. I'm aware of several reports of B12 deficiency from NO abuse, but I haven't seen any reports of withdrawal symptoms.