This mastery is intended for champions that utilize a large mana pool (mainly mages) but occasionally need to get close to enemies (perfect examples would be Singed, Blitzcrank and Ryze).
Be careful when relying on Strength of Spirit's health regeneration for your survivability needs. Even at max rank, this mastery is deceptively inadequate; it is meant to compensate for a mage's low survivability in assistance to a cautious behaviour. Low-health mages with short spell range typically utilizing this mastery are wiser than keeping too close to enemies.
Keep in mind that since Strength of Spirit scales with maximum mana, it would not compare to the effectiveness of health regenerationitems: they immediately increase health regeneration and also provide other beneficial effects.
It is exceptionally strong on Ryze as he normally ends up with large amounts of mana since his abilities scale with maximum mana as well.
Accordingly, it synergizes well with spell vamp effects.
The effect is based off the champion's total maximum mana, including mana increases from masteries, runes and items.
The maximum HP Regen per 5 that can be gained in the game utilizing Strength of Spirit is approximately 76.33 from the maximum possible mana of 7632.765.