This novel study assessed the tolerance of an ICKD, the feasibility of a bike performance test under hypoxic condition and gathered preliminary data on effects of shifting from a HD to an ICKD on VO2max under a simulated very high-altitude condition. We used maximal graded exercise bike tests for assessing endurance parameters and post-exercise arterial blood samples for assessing oxygenation and pH status. We hypothesized that a reduced CHO intake would increase VO2max performance parameters under hypoxia. To our knowledge, these aspects were never investigated before.
All participants except one could complete the ICKD. The recorded values for this participant were out of CHO limitation and his data thus excluded from data analysis. This emphasis the need of a strict diet follow-up and blood KB analysis. Another participant dropped out because of a personal schedule mismatch. This underlines the importance of a high motivation and collaboration between researchers and participants in particular because of the high number of maximal graded exercise bike test with standardized time between the tests. Overall, only minor adverse events such gastro-intestinal complains at the beginning of the diet or weight loss were reported but none of the participants had to stop the ICKD.
With a median intake for HD and ICKD were below typical energy requirement(41) so participants were in negative energy balance.
Moreover, we identified two major difficulties for participants to follow the ICKD. First, high exercises load training turned out to be difficult during the first weeks of an ICKD diet.. Indeed, there was a subjective performance drop at the beginning of the new diet because of ICKD adaptation(42). Second, participants also reported a social impact during the ICKD.
Evaluating participant’s ICKD performances benefit in hypoxic condition
We evaluated ICKD-induced performance benefit in hypoxic condition by using a maximal graded exercises bike test. The observed decrease of performance parameters VO2max, PLT, Ppeak and PaO2 when exposed to hypoxia strengthen the reliability of results and the feasibility of our protocol.
Effect of Hypoxia
Hypoxia induced for every participant a clear decrease in VO2max by 13 ml.kg− 1.min− 1 (-27.01%), Ppeak by 60W (-22.4%), and PaO2 by 8.8 KpA(-50.9%) (Table 2). This was expected as the primary limitation for VO2max under hypoxic conditions is oxygen tissue availability(43). Indeed, significant drop of VO2max were previously reported with acute exposition to hypoxia(35–37). This results from the dropping of the barometric pressure with increasing altitude. Therefore PIO2 and consequently oxygen transport decrease(35, 44). A research compilation by Robergs and Robert (1997) reported an average decrement of VO2max by 8.7% per 1000m(45). Nevertheless, it is not appropriate to express an average value as there is a highly inter-individual variation in the reduction of VO2max depending on sea level VO2max, gender, sea level LT and lean body mass(22). This may explain the large range of VO2max drop (-36.5% to -20.3%) in our study. Furthermore, we noticed no significant difference in arterial blood pH, PaCO2 and HCO3.
Effect of ICKD on performance parameters
VO2max (+ 7.3%) and Ppeak (+ 4.7%) improvement with a 4-week ICKD under hypoxic condition in 4 out of 6 participants (Tables 3 and 4) do not allowed conclusion on the effects of KD. We noticed no performance marker which is systematically affected by ICKD. This recorded improvement has been similarly partially reported in normoxia(17, 25). VO2max reflects the cardiorespiratory fitness(46) and is considered as a gold standard for measuring aerobic metabolism(47). A greater VO2max indicates greater endurance capacity. Actual known factors influencing VO2max are age, gender, heredity, body composition, state of training and mode of exercise(48).
KD has been newly identified as a potential positive factor for VO2max(19, 23, 25, 26) by shifting mitochondrial metabolism(5, 17). These studies were summarized by Bailey et al. (2020)(17). They suggest that several factors such as genetic variation, trainability and or chronic substrate utilization may be influenced by KD, which consequently might increase VO2max. The positive effect of ICKD on VO2max under hypoxic condition observed in our study strengthened the idea that a high-fat ingestion might be beneficial for an endurance exercise under an acute hypoxia exposition.
In addition, further performance LT parameters were improved in two participants considered as ICKD-responder (Table 5). As showed in Fig. 3, B-Lac kinetic is lower with ICKD. Points for LT and maximal value are shifted to the right (right curve-shifting). HR kinetic is higher with ICKD. Points for LT and maximal values are at higher power (left curve shifting). LTs are performance indicators which strongly correlate with endurance performances (40). It represents aerobic-anaerobic transition because lactate kinetic is highly related to the metabolic rate and less to oxygen availability(40). A higher workload to a given blood lactate concentration can be interpreted as an improved endurance capacity(49). Previous studies have reported a shift in B-Lac curve to higher workloads under KD condition(50). This phenomenon is still not fully understood but a relationship with a decreased glycolysis rate or limited lactate efflux from muscle due to reduced blood buffering capacity is hypothesized(23, 50). Further, depleted glycogen stores (due to e.g. ICKD) is a known factor leading to lower lactate blood concentration at the same work rate(51).
In this context and considering key performance parameters (VO2max, PLT, HRLT and Ppeak), we profiled the 6 participants either as ICKD responders or ICKD non-responders. ICKD responders showed a right-shifting in B-Lac kinetics (Fig. 3) which can be interpreted as a better performance test(49). Peak values (Ppeak and VO2max) also demonstrated a better performance. HR-curve left shifting showed a higher HR work range with ICKD. For ICKD non-responders, the intervention showed little to no effect, and ICKD- and HD-tests were superimposable. The variations were probably mostly due to the physical condition of the participants on that day. One participant clearly worsened his global ICKD-performance at every time point without clear explanation. Several factors could be a reason including bad day shape, or influence of ICKD on age-related VO2max-factors like decline in maximal hearth rate, stroke volume, fat-free mass and arterio-veinous oxygen differences(52).
Effect of ICKD on blood gases
ICKD showed post-exercise PaO2 decrease in all participants (-14.5%), a response confirmed in cross-over group B when returning to HD (+ 14.5%). A physiological approach allows explaining the ICKD related hypoxemia. PaO2 is determined by alveolar PO2 (PAO2), ventilation, diffusion capacity of the lung and perfusion by the heart. It is well described that PAO2 depends on the respiratory gas-exchange ratio (RER). RER is the ratio between CO2 pulmonary output () and O2 uptake () expressed as. This can be drawn to the alveolar air equation. RER depends in the steady state (like by resting) on the food metabolized(53). ICKD increases fat oxidation, lowers RER (~ 0.7) and consequently PAO2 and PaO2 decrease(53). Furthermore, maximal graded test is not a steady state and RER varies with exercises. Within a few minutes into recovery RER fall below 0.7 as ventilation declines and the CO2 store re-increases(54). Decreased ventilation could also influence PaO2. This is observed in respiratory failure, a well-known process in diabetic ketoacidosis. Ketosis is generating a respiratory response in form of hyperpnea(55). This leads to respiratory muscles fatigue (known as Kussmaul respiration)(56). ICKD could lead to a mismatch of the lung maintaining PaO2 by a form of respiratory muscle fatigue due to KB.
Alternative explanation concerning influence of heart perfusion on PaO2 is not relevant. Although, KB can influence heart flow, it increases the hydraulic efficiency of the heart rather than decreasing it(16). The higher heart flow rate leads to an increase in pulmonary venous blood admission. Finally, CHO are known to increase PaO2 at high-altitude by increasing the relative production of carbon dioxide so increasing the drive for ventilation(57).
Consistent with a previous study made by Hansen et al (1967)(54), ICKD worsened the hypoxemia in our simulated very high-to extreme altitude (> 3500 m.). This is a relevant limitation of using ICKD diets above a very high-altitude(44, 58), whereas at high-altitude (1500–3500 m.), PaO2 is significantly diminished but with only minor impairments in oxygen transport (SaO2 > 90%)(44). ICKD could therefore be used for this altitude.
Arterial blood sampling also showed a nonsignificant effects on the pH (+ 0.278%) post-exercise that is below analytical precision... It could be expected a increased pH asKB are acids known to induce ketoacidosis(59, 60). Nevertheless, Carr et al. (2018) contrasted these earlier beliefs by describing minimal effects of KD on acid base status in elite athletes(19). They also reported no statistical blood pH differences between high CHO vs high fat in pre- and post-exercises.. Blood pH stability is possibly due to higher exercise induced ventilation rate and so would increase the pH.
In conclusion our preliminary data showed a benefit of ICKD on performance parameters. A positive increment on VO2max (primary outcome) and further LT performance parameter (secondary outcome) could be recorded. ICKD intervention decreased however PaO2, a observation which is consistent with previous studies(54) and may limit ICKD application in very high altitude.