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Setting non-binary columns to null in a table with a binary column populated with data creates free space and a larger file
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Consider the following table schema:

CREATE TABLE [Data1](
  [Data] BLOB, 
  [Items_id] INTEGER, 
  [Key] TEXT);

If there is a row with the following data and the database is vacuumed:
[Data] = <very large binary>, Items_id = 1, Key = "MyKey"

And we issue the following command:
UPDATE Data1 SET Items_id = null, Key = null WHERE Items_id = 1;

The database file size on disk appears to double and the 'Pages on the freelist' is 50% when using sqlite3_analyzer in the summary output.