I've used 4.9 mm small cell since 2005 which gives 12 years of experience. Dee Lusby was the first to latch onto small cell when she determined that it is closer to the natural cells bees build. She is using africanized bees which are a bit smaller than most European races so technically, she is correct that 4.9 is right for her bees.
5.3 or 5.4 foundation is a tad larger than the average cell most bees produce when drawing their own comb. From documents you can find online, A.m. mellifera, A. m. Carnica, and A. m. Major Nova (from the Rif mountains) naturally make larger cells. Equatorial races from Africa tend to make smaller cells and smaller bees on average. Bees from colder climates tend to be larger.
The range of cell sizes in naturally built combs for worker cells is 4.3 mm to 5.7 mm with an average of 5.1 mm. (See Huber as one reference for measurements) Bees will build a few cells both larger and smaller but they won't raise worker brood in them. They will raise drones in cells from roughly 6.2 mm to 7.5 mm with the average drone cell just under 7.0 mm. There is good evidence that raising bees in larger cells selected for bees that are larger and prefer the larger cell size. Bee measurements from 120 years ago strongly support 5.1 mm as the average cell size at that time. Measurements made recently support 5.3 as the average in naturally built comb.
Jennifer Berry ran a fairly decent trial a few years ago comparing bees on 5.4 vs bees on 4.9 and reached the conclusion that cell size does not significantly affect varroa mite infestation levels. You can easily find this study online so I won't link it. In my opinion, this was a huge red herring. There are benefits to using small cell, but not for managing varroa.
Negatives: It is a pita to get the bees to draw 4.9 properly in the first place, the bees naturally tear down and rebuild it to the size they want, and it is awkward in other ways to manage, mostly depending on the race of bees. Once bees are successfully on small cell, they will use it and quickly adapt to producing brood in it.
Positives: The brood nest is more compact with small cell. This has a small but significant impact on spring buildup because a given size cluster of bees can cover more cells of brood.
If you can get bees that are naturally a bit smaller, they will readily adapt to small cell. If you start with the average Carnica colony, they will make a mess of it. I have bees that are a tad smaller and naturally prefer small cell.
If I had it all to do over again? Well, I am doing it all over again by converting to square Dadant (Brother Adam) hives which means all my Langstroth size frames have to be replaced. I build my own frames at 31.5 mm spacing. This is significantly closer frame spacing than most beekeepers use with 35 mm for Langstroth and 38 mm for Dadant frames. The reason I use 31.5 mm spacing is because spring buildup is faster than on wider spaced frames. This is important to make surplus honey from spring maple and fruit bloom. I found that combining 31.5 mm frame spacing with small cell combs enhances spring buildup. My bees typically reach peak strength in 8 weeks vs 10 to 12 weeks on large cell combs at wider spacing. Is this important? In my climate, yes, it is helpful, check your local climate and spring buildup to see if your bees would benefit.
I was unable to source 5.1 foundation this past spring so the roughly 200 combs my bees built this year are all 5.4. I contacted Dadant earlier this year and arranged to have them run 200 pounds of 5.1 foundation in 10 5/8 inch sheets. I will use it next year for all the center brood frames and gradually cycle out the 5.4 frames over the next few years. I expect them to ship the 5.1 foundation later this month. Dadant 10 5/8 foundation runs 128 sheets from 25 pounds of wax, a tad over 5 sheets per pound.
tldr: I like the effect of small cell foundation combined with 31.5 mm frame spacing.
https://articles.extension.org/page...mb-cell-size-with-49-mm-i-have-heard-that-sma