Published alkenone ε p records spanning known glacial pCO 2 cycles show considerably less variability than predicted by the diffusive model for cellular carbon acquisition and isotope fractionation. We suggest this pattern is consistent with a systematic cellular enhancement of the carbon supply to photosynthesis via carbon concentrating mechanisms under the case of carbon limitation during low pCO 2 glacial time periods, an effect also manifest under carbon limitation in experimental cultures of coccolithophores as well as diatoms. While the low-amplitude ε p signal over glacial pCO 2 cycles has led some to question the reliability of ε p for reconstructing long-term pCO 2 , the [CO 2 ] aq in the tropical oceans during glacial pCO 2 minima represents the most extreme low CO 2 conditions likely experienced by phytoplankton in the Cenozoic, and the strongest upregulation of carbon concentrating mechanisms. Using a statistical multilinear regression model, we quantitatively parse out the factors (namely light, growth rate, and [CO 2 ] aq ), that contribute to variation in ε p in alkenone-producing algae, which confirms a much smaller dependence of ε p on [CO 2 ] aq in the low [CO 2 ] aq range, than inferred from the hyperbolic form of the diffusive model. Application of the new statistical model to two published tropical ε p records spanning the late Neogene produces much more dynamic pCO 2 estimates than the conventional diffusive model and reveals a significant pCO 2 decline over the last 15 Ma, which is broadly consistent with recent results from boron isotopes of foraminifera. The stable isotopic fractionation between coccolith calcite and seawater dissolved inorganic carbon (here Δ coccolith-DIC ) also shows systematic variations over glacial-interglacial cycles which may, following future experimental constraints, help estimate the degree of upregulation of parts of the algal carbon concentrating mechanism over glacial cycles.