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The isomerization of alpha acids into iso-alpha acids is mostly dependent on alpha acid content, time (to a certain extent), temperature, original gravity, hop rate (hop mass), and IBU saturation. Other variables also affect isomerization to a lesser extent such as pH and calcium concentration <ref>[https://onlinelibrary.wiley.com/doi/pdf/10.1002/j.2050-0416.1964.tb06356.x CHANGES IN HOP ACIDS CONCENTRATIONS ON HEATING IN AQUEOUS SOLUTIONS AND UNHOPPED WORTS. H. O. Askew. 1964.]</ref><ref>[http://pubs.acs.org/doi/abs/10.1021/jf0481296 Isomerization and Degradation Kinetics of Hop (Humulus lupulus) Acids in a Model Wort-Boiling System. Mark G. Malowicki and Thomas H. Shellhammer. 2005.]</ref><ref name="justice_2018">[https://www.mbaa.com/publications/tq/tqPastIssues/2018/Pages/TQ-55-3-1205-01.aspx Tracking IBU Through the Brewing Process: The Quest for Consistency. Aaron Justus. Director of R&D and Specialty Brewing, Ballast Point Brewing. MBAA TQ 2018; vol. 55, no.3. https://doi.org/10.1094/TQ-55-3-1205-01.]</ref>. The higher the gravity of wort above 1.050 SG, the more proteins coagulate and drop iso-alpha acids out of solution (lower gravity worts are not affected). During fermentation, yeast cells can absorb iso-alpha acids, which results in further loss of iso-alpha acids in the finished beer <ref name="Bastgen_2019" />. Lower flocculating yeast strains tend to reduce the IBU in finished beer more than high flocculating yeast. Significant isomerization of alpha acids can occur in water without sugar at all (temperatures around boiling are still required), which is relevant in the production of [http://www.garshol.priv.no/blog/331.html "hop tea" in traditional farmhouse brewing] where hops are steeped in hot water for some time, and this is said to extract bitterness from the hops <ref>[http://www.ijbbb.org/papers/161-E005.pdf Kinetic Modeling of Hop Acids during Wort Boiling. Yarong Huang, Johannes Tippmann, and Thomas Becker. 2013.]</ref><ref>[http://www.garshol.priv.no/blog/331.html Lars Marius Garshol. "Raw ale". Larsblog. 05/06/2015. Retrieved 12/17/2018.]</ref>. Malowicki and Shellhammer determined a calculation that predicts the isomerization rates of alpha acids into iso-alpha acids at different temperatures. Beginning at the boiling temperature of 100°C/212°F, which could be considered a rate of 100%, at 96°C/205°F the rate is 72%, and at 90°C/194°F the rate is 43%. This rate continues to drop significantly as the temperature of the wort decreases. At 82°C/180°F isomerization occurs at a rate of 17%. At a temperature of 50°C/122°F, the isomerization rate is at 1%, and finally 0% at 45°C/113°F. This fact has several impacts on brewing processes. For example, when brewing at higher altitudes where the boiling point of wort is less than 100°C/212°F, the isomerization of alpha acids into iso-alpha acids will be reduced to whatever the rate is at that lower temperature. "Hop stands" or "whirlpool additions" where hops are left in contact with hot wort that is less than boiling temperature will continue to isomerize alpha acids <ref>[https://www.mbaa.com/publications/tq/tqPastIssues/2017/Pages/TQ-54-3-0806-01.aspx A Look at Isomerization Reduction Due to Altitude. John Palmer. MBAA TQ 2017 http://dx.doi.org/10.1094/TQ-54-3-0806-01.]</ref>.
The hopping rate (mass) has and IBU saturation have a drastic effect on IBU's for 60 minute additions. Aaron Justice reported a higher utilization when using Polaris hops (17.6% alpha acids) versus Tettnang hops (1.9% alpha acids). Two beers were brewed using enough of each of the hop varieties to target a calculated 40 IBU. However, the beer brewed with Polaris hops had 42.6 IBU and the beer brewed with Tettnang hops had only 28 IBU. It was hypothesized that the higher surface area of more hop matter reduces IBU's by binding to iso-alpha acids and possibly other compounds that register on the standardized IBU test. Justice also reported that more IBU pickup from whirlpooling was possible in beers without hops added in the kettleboil, indicating that IBU saturation can limit IBU's, with a maximum IBU being around 100 <ref name="justice_2018" />.
The pH of the wort can also have a small effect on the isomerization of alpha acids to iso-alpha acids, although less significant than alpha acid content, time (to a certain extent), temperature, and original gravity. Aaron Justice reported a slight rise in utilization of hops ("utilization" as being the conversion of alpha acids to iso-alpha acids) when the boil pH was raised from 5.05 to 5.35 <ref name="justice_2018" />. Bastgen et al. (2019) found that at a boil pH of 5.6, the percentage of iso-alpha acids increased by 32% by extending the boil from 60 minutes to 120 minutes. However, there was no increase at all in iso-alpha acids when the boil pH was 7, but a pH of 7 is not typical in the brewing process <ref name="Bastgen_2019" />. Time is thought to play a large role in isomerization, however, Justice reported that the majority of the IBU from iso-alpha acids in 60 minute additions and in whirlpool additions occurs within the first 10 minutes, with only a 12-30% increase after another 50 minutes of boiling/whirlpooling (higher gravity beers had more isomerization during the final 50 minutes while lower gravity beers had less isomerization during the final 50 minutes of boiling) <ref name="justice_2018" />.