Citation: Roberts, J.D.; Lillis, J.B.;
Pinto, J.M.; Chichger, H.;
López-Samanes, Á.; Coso, J.D.; Zacca,
R.; Willmott, A.G.B. The Effect of a
Hydroxytyrosol-Rich, Olive-Derived
Phytocomplex on Aerobic Exercise
and Acute Recovery. Nutrients 2023,
15, 421. https://doi.org/10.3390/
nu15020421
Academic Editor: David C. Nieman
Received: 14 December 2022
Revised: 6 January 2023
Accepted: 10 January 2023
Published: 13 January 2023
Copyright:
© 2023 by the authors.
Licensee MDPI, Basel, Switzerland.
This article is an open access article
distributed
under
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terms
and
conditions of the Creative Commons
Attribution (CC BY) license (https://
creativecommons.org/licenses/by/
4.0/).
nutrients
Article
The Effect of a Hydroxytyrosol-Rich, Olive-Derived
Phytocomplex on Aerobic Exercise and Acute Recovery
Justin D. Roberts 1,*
, Joseph B. Lillis 1, Jorge Marques Pinto 1
, Havovi Chichger 2
, Álvaro López-Samanes 3
,
Juan Del Coso 4
, Rodrigo Zacca 5,6
and Ashley G. B. Willmott 1
1
Cambridge Centre for Sport and Exercise Sciences (CCSES), School of Psychology and Sport Science,
Anglia Ruskin University, Cambridge CB1 1PT, UK
2
School of Life Sciences, Anglia Ruskin University, Cambridge CB1 1PT, UK
3
Exercise Physiology Group, Faculty of Health Sciences, Universidad Francisco de Vitoria, 28223 Madrid, Spain
4
Centre for Sport Studies, Rey Juan Carlos University, 28943 Fuenlabrada, Spain
5
Research Center in Physical Activity, Health and Leisure (CIAFEL), Faculty of Sports, University of
Porto (FADEUP), 4200-450 Porto, Portugal
6
Laboratory for Integrative and Translational Research in Population Health (ITR), 4050-600 Porto, Portugal
*
Correspondence: justin.roberts@aru.ac.uk; Tel.: +44-845-196-5154
Abstract: There is current scientiﬁc interest in naturally sourced phenolic compounds and their
potential beneﬁts to health, as well as the effective role polyphenols may provide in an exercise setting.
This study investigated the chronic effects of supplementation with a biodynamic and organic olive
fruit water phytocomplex (OliPhenolia® [OliP]), rich in hydroxytyrosol (HT), on submaximal and
exhaustive exercise performance and respiratory markers of recovery. Twenty-nine recreationally
active participants (42 ± 2 yrs; 71.1 ± 2.1 kg; 1.76 ± 0.02 m) consumed 2 × 28 mL·d−1 of OliP or
a taste- and appearance-matched placebo (PL) over 16 consecutive days. Participants completed a
demanding, aerobic exercise protocol at ~75% maximal oxygen uptake (
.
VO2max) for 65 min 24 h
before sub- and maximal performance exercise tests prior to and following the 16-day consumption
period. OliP reduced the time constant (τ) (p = 0.005) at the onset of exercise, running economy
(p = 0.015) at lactate threshold 1 (LT1), as well as the rating of perceived exertion (p = 0.003) at lactate
turnpoint (LT2). Additionally, OliP led to modest improvements in acute recovery based upon a
shorter time to achieve 50% of the end of exercise
.
VO2 value (p = 0.02). Whilst OliP increased time to
exhaustion (+4.1 ± 1.8%), this was not signiﬁcantly different to PL (p > 0.05). Phenolic compounds
present in OliP, including HT and related metabolites, may provide beneﬁts for aerobic exercise
and acute recovery in recreationally active individuals. Further research is needed to determine
whether dose-response or adjunct use of OliP alongside longer-term training programs can further
modulate exercise-associated adaptations in recreationally active individuals, or indeed support
athletic performance.
Keywords: polyphenols; OliPhenolia®; hydroxytyrosol; exercise; oxygen uptake kinetics; lactate
threshold; running economy
1. Introduction
Nutritional strategies to enhance exercise performance and recovery are of current
scientiﬁc interest to individuals who regularly undertake physical activity, competitive
athletes, military workers, as well as the general population. Recent approaches which
have gained popularity in an attempt to attenuate exercise-induced muscle damage (EIMD)
and oxidative stress include the supplementation of naturally occurring phytochemicals
(i.e., polyphenols) from sources such as pomegranate, cocoa, or cherries [1–3]. The average
adult consumption of polyphenols is suggested to be ~1 g·d−1 [4], with primary sources
from fruits, vegetables, beverages such as tea and coffee, wine, and chocolate [5]. With
antioxidant properties [6], nutritional polyphenols may act as radical scavengers and metal
Nutrients 2023, 15, 421. https://doi.org/10.3390/nu15020421
https://www.mdpi.com/journal/nutrients
Nutrients 2023, 15, 421
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chelators, regulating metabolism, body mass, chronic disease, and cell proliferation [7]. Free
radicals and reactive oxygen and nitrogen species (RONS) are the primary oxidizing agents
produced in cellular biochemical reactions for aerobic energy production [5]. Aerobic
exercise is characterized by increased total energy expenditure [8], where the availability of
endogenous substrates and aerobic metabolism are crucial for overall performance [9,10].
The increased oxygen (O2) demand by skeletal muscles during exercise results in greater
free radical production and an increase in RONS [11]. Whilst viewed as detrimental to the
cell for many years, recent evidence shows that RONS are crucial physiological activators
and regulators of various intracellular signaling pathways in response to stress, enhanc-
ing defense, improving cell adaptation, and upregulating the expression of endogenous
antioxidant enzymes [12,13].
Furthermore, exercise adaptations are dependent, at least partially, on an acute ox-
idative stress response. When exercise intensity is matched, individuals expressing lower
levels of RONS have demonstrated inferior training adaptations compared to those with
moderate or higher levels of RONS [14]. However, during excessive and demanding exer-
cise, an imbalance between RONS and endogenous antioxidants induces oxidative damage,
potentially impacting at a mitochondrial or DNA level [15], reducing vasodilatory capac-
ity [16] and contractile force within the muscle through impaired calcium sensitivity [17].
This can have inferences for repetitive training sessions or longer-term adaptations and may,
therefore, impair exercise performance and/or the recovery process. In sports where arterial
blood flow and maximum cardiac output are determinants of performance (i.e., endurance
and team-based sports), acute ingestion (<3 h before competition) or chronic supplementation
of polyphenols (~7-days) could improve time to exhaustion at 70% maximum oxygen uptake
(
.
VO2max) by +9.7% [18] and intermittent high-intensity running distance by +10% [19].
The mechanisms by which polyphenols may facilitate ergogenic effects reportedly
occur via nitric oxide synthase production [20] as well as the activation of sirtuin 1
(SIRT1) [21,22]. SIRT1 deacetylates several transcription factors such as forkhead (FOXO)
proteins and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-
1α) [23]. This can facilitate mitochondrial biogenesis, endothelial function, cell proliferation
and differentiation, metabolic efﬁciency, resistance to stress, and improve inﬂammatory and
immune function [24–26]. The supplementation of phenolic compounds, and gut-derived
metabolites, may therefore provide adjunct or indirect ergogenic effects on physical perfor-
mance by way of potentially reducing the O2 cost of exercise (i.e., economy), enhancing
.
VO2max or exercise tolerance, and/or improving substrate utilization efﬁciency. Previ-
ous ﬁndings have highlighted that polyphenol nutrients (e.g., resveratrol) may support
mitochondrial function [27] and may therefore modulate essential biological functions
(including thermogenesis, mitochondrial biogenesis and adenosine triphosphate produc-
tion) [28]. These functions are pivotal for trained, recreationally active and untrained
exercising individuals, ensuring that substrate supply kinetics and waste product removal
match the requirements of the speciﬁc exercise bout [29].
Furthermore, it could be inferred that due to the anti-inﬂammatory and immuno-
modulatory effects of phenolic compounds, an increase in polyphenol consumption (from
food or supplementation) may be pertinent to exercise recovery. A reduction in physio-
logical stressors that negatively impact exercise training [30] may support fast and slow
phases of recovery, inﬂuencing performance in both prolonged or repeated bouts of exercise.
Evidence for enhanced functional recovery from foods/supplements high in polyphenol
compounds (e.g., Montmorency cherries > 5-days) have been exhibited in both trained and
untrained individuals in a multitude of general exercise settings [31–33]. However, further
research is warranted to investigate other polyphenols or novel food products, to assess
markers of exercise recovery and identify the potential impact of phenolic compounds in
speciﬁc exercise settings.
This is the ﬁrst study to undertake an investigation into a commercially available
polyphenol-rich olive fruit water, OliPhenolia® (OliP), which has not been assessed in an
exercise domain. Originating during the olive picking season, this polyphenol-rich drink
Nutrients 2023, 15, 421
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is extracted via concentration, reverse osmosis, and ceramic membrane technology at the
aqueous part of the olive fruit. Whilst OliP contains a variety of phenolic compounds, it
is particularly rich in hydroxytyrosol (HT). Abundant in olives in the form of pure HT, HT
glycosides and oleuropein, HT is an effective antioxidant, with studies highlighting protection
against oxidative stress in vascular tissue [34,35], low-density lipoprotein oxidation [36–38],
and a reduction in oxidative damage in intestinal epithelial cells [39], hepatocytes, and
erythrocytes [40]. However, OliP has yet to be considered within an exercise and/or
recovery domain and thus, requires investigation. Therefore, this study investigated the
effect of OliP on submaximal and exhaustive exercise, as well as respiratory markers of
acute recovery, in recreationally active volunteers. Understanding the efﬁcacy of OliP may
inform future nutritional strategies pertinent to exercise training and recovery.
2. Materials and Methods
2.1. Ethical Approval and Trial Registration
This study was registered with clinical-trials.gov (ID: NCT04959006) with ethical
approval obtained from the Faculty of Science and Engineering Research Ethics Panel,
Anglia Ruskin University (Ethical approval no. FSE/FREP/20/946). Following a priori
power calculation (G*power3, Dusseldorf, Germany [41]) using α = 0.05 and 1-β = 0.80,
from previous reports of a time trial run and following recovery (plasma free radicals, post
run pain and time to recovery [h]) [42], a minimum sample size of eight per intervention
group was estimated.
2.2. Participant Characteristics
Eligibility for the study required participants to be recreationally active (undertaking
~3 exercise sessions a week), with a
.
VO2max of >25 mL·kg−1·min−1 determined at the ﬁrst
visit. All participants were >21 yrs, with no known metabolic disorders, viruses, or infec-
tions; were not self-administering any polyphenol or antioxidant-rich supplementation or
adhering to speciﬁc diets that could conﬂict with study parameters. A total of 32 healthy
participants volunteered and engaged with the study. However, following a review of indi-
vidual protocol adherence and analysis of outliers, 3 participants’ datasets were removed.
General characteristics of the remaining 29 participants satisfactorily completing the study
are displayed in Table 1.
Table 1. Mean ± standard error (SE) participant characteristics overall and for OliPhenolia® (OliP)
and placebo (PL) groups respectively.
Variable
Overall
OliP
PL
(n = 29; 20 M, 9 F)
(n = 15; 11 M, 4 F)
(n = 14; 9 M, 5 F)
Age (yrs)
42 ± 2
42 ± 3
42 ± 3
Height (m)
1.76 ± 0.02
1.77 ± 0.03
1.75 ± 0.03
Body mass (kg)
71.08 ± 2.14
73.57 ± 2.44
68.41 ± 3.52
Fat free mass (kg)
57.67 ± 2.31
59.33 ± 3.05
55.89 ± 3.56
Body mass index (kg·m2)
22.9 ± 0.4
23.5 ± 0.4
22.3 ± 0.7
Body fat (%)
18.7 ± 1.8
19.5 ± 2.2
17.8 ± 3.0
.
VO2max (L·min−1)
3.53 ± 0.16
3.56 ± 0.22
3.49 ± 0.24
.
VO2max (mL·kg−1·min−1)
49.6 ± 1.7
48.3 ± 2.5
51.0 ± 2.2
M = male; F = female;
.
VO2max = maximal oxygen uptake. No statistical differences were reported between groups
(p > 0.05).
2.3. Experimental Design
Using a randomized number generator process (www.randomizer.org; accessed on 10
May 2021), participants were allocated into two supplement intervention groups (OliP or
PL) in a double-blind manner. All participants reported to the Cambridge Centre for Sport
and Exercise Sciences (CCSES), Anglia Ruskin University, on ﬁve separate occasions, the
ﬁrst of which involved an initial familiarization session [43,44]. All laboratory visits were
Nutrients 2023, 15, 421
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conducted at the same time of day following an overnight fast (~10 h), with participants
arriving in a euhydrated state. Participants were instructed to avoid strenuous and/or
excessive exercise for the 24 h prior to testing visits, as well as adhere to all dietary instruc-
tions for the 3-days pre-testing (Section 2.4). For the duration of the supplementation period,
participants were asked to continue habitual exercise and diet regimes, ensuring each week
was matched to the previous in terms of training load, caloric and macronutrient intake.
2.4. Dietary and Exercise Activity Monitoring
Dietary and hydration intake was tracked via the use of a mobile based application
(MyFitnessPal, Inc., San Francisco, CA, USA). Participants were provided with a personal
login and guidance instructions to support detailed dietary tracking. Participants were
required to record consumption of all food items and liquids for 3-days leading into each
exercise test as part of this study, as well as across the 16-day intervention period [45] and
were checked regularly by the same researcher for consistency throughout the intervention.
A list of polyphenol-rich ‘foods to avoid’ was also provided for participants to adhere to
in the 3-days leading into each laboratory visit (see Supplementary Materials, Table S1).
Participants were also required to complete a standardized, daily exercise activity diary for
the 3-days prior to exercise trials and the duration of the 16 consecutive days supplementa-
tion period, ensuring they were rested for the 24 h prior to each visit. Participants were
requested to maintain habitual lifestyle and exercise patterns across the study, ensuring
consistency across the 16-day period throughout the course of supplementation. Session
type, mean session heart rate, exercise duration and perceived session exertion (using
a standard 0–10 visual analogue scale) were recorded following the completion of each
training session as reported elsewhere [45].
2.5. Laboratory Procedures
All tests took place under controlled environmental conditions (temperature: 19.6 ± 0.3 ◦C;
barometric pressure: 1005.6 ± 1.2 mBar; and relative humidity: 48.4 ± 2.2%). Upon arrival,
participants rested for 10 min in a seated position before assessment of blood pressure
(Omron 750CP, Kyoto, Japan), body mass (electronic scale, Seca, Hamburg, Germany),
and height (Seca stadiometer, Hamburg, Germany). At rest (baseline) and throughout
exercise, 20 µL capilliarized ﬁngertip blood samples were collected for the assessment of
blood lactate and glucose (Biosen C Line EKF-diagnostic analyzer, Cardiff, UK). Heart rate
(HR) data were recorded in 5 s intervals using a short-range telemetric monitor (Polar 810s,
Polar T34 strap, Kempele, Finland). For the initial familiarization trial, body composition
was also recorded using bioelectrical impedance for the indirect assessment of body fat
percentage, fat-free mass, and fat mass (Tanita SC-330ST, Amsterdam, The Netherlands).
Breath-by-breath pulmonary gas variables (volume of O2 [
.
VO2], volume of carbon dioxide
[
.
VCO2], minute ventilation [
.
VE], respiratory exchange ratio [RER], breathing frequency
[BF] and tidal volume [TV]) were measured continuously via a metabolic cart (MetaLyzer
3B-R2, Cortex Ltd., Leipzig, Germany) using a suitable facemask for each participant (7600
face mask with headgear, Hans Rudolph, Shawnee, Kansas, USA). Prior to each test, the
MetaLyzer was calibrated as per manufacturers’ speciﬁcations. All exercise testing was
completed on a Quasar Med Treadmill (HP Cosmos, Nussdorf, Germany).
2.5.1. Experimental Protocols—Visit 1, 3 and 5
Exercise intensities were calculated using lactate proﬁles from the familiarization trial
(visit 1) and remained consistent in visit 3 and 5. Visits 1, 3 and 5 consisted of a two-part
graded exercise test [46,47] including: (1) a submaximal incremental protocol, with a 10 min
recovery period; and (2) a maximal test to volitional exhaustion (Figure 1).
Nutrients 2023, 15, 421
5 of 20
 
3 min 
10 min 
Ramp to volitional 
exhaustion 
Recovery 
B 
B 
B 
B 
5 min 
50 min 
1 min 
60% ∆ LT1−LT2 
10% above LT2 
LT1 speed 
1 h 
3 min 
10 min 
Ramp to volitional 
exhaustion 
Recovery 
24 h 
Visit 5: Repeat of visit 3 
Visit 4: Repeat of visit 2 
Visit 1: Familiarization session 
Visit 2: Demanding aerobic session  
Visit 
3: 
Submaximal 
and 
performance test session  
16-day intervention 
24 h 
≥3-days 
End of study 
Figure 1. Schematic of study protocol outlining the familiarization (visit 1), demanding aerobic session
(visit 2) and submaximal and performance test session (visit 3). B = blood sample; LT1 = lactate
threshold; LT2 = lactate turnpoint.
2.5.2. Submaximal and Performance Test Protocol
The speed for the submaximal protocol was selected at a pre-deﬁned level and in-
creased by 1 km·h−1 every 4 min, with 3 min of running at a constant speed [46,47] followed
by a 1 min break for capilliarized ﬁngertip blood sample collection. The gradient was main-
tained at 1% [48] with rating of perceived exertion (RPE; 0−10 scale) and HR assessed in
the ﬁnal 30 s of each running stage. For the
.
VO2max performance test, speed was held con-
sistent with gradient increasing by 1% per min, with RPE and blood lactate concentration
(B[La]) obtained at the end of the test. Participants ran until volitional exhaustion (which
determined time to exhaustion [TTE]), with standardized verbal encouragement provided
towards the end of the test.
2.5.3. Determination of Physiological Parameters and Respiratory Kinetics
Lactate threshold (LT1) was determined by an initial rise in B[La] above baseline [49],
and lactate turnpoint (LT2) was determined by a sudden and sustained increase in B[La] [50].
Nutrients 2023, 15, 421
6 of 20
Mean and standard deviations (SD) of
.
VO2 for the last 30 breaths of each increment
were calculated. Values ±4 SD were removed as outliers with all remaining breaths
averaged [44].
Running economy was calculated in mL·kg−1·km−1 [51], described in Equation (1) below:
Economy =
.
VO2

mL·kg−1·min−1
Speed (km·h −1)/60
(1)
The
.
VO2 kinetics for exercise (on-kinetics) and recovery periods (off-kinetics) were
modelled and calculated using validated software VO2FITTING [52]. Errant breaths were
omitted by only including those within
.
VO2 local mean ± 4 SD. Subsequently, the individ-
ual on-transient breath-by-breath
.
VO2 responses were modelled using a mono-exponential
model [52] described in Equation (2):
.
VO2(t) =
.
VO2baseline + A

1 − e− t
τ

(2)
where
.
VO2(t) represents the relative
.
VO2 at the time t, A and τ are the amplitude and time
constant (τ) of the fast
.
VO2 component. The individual off-transient breath-by-breath
.
VO2
responses were modelled using the a mono-exponential model [52] described in Equation (3):
.
VO2(t) = EE
.
VO2 − A

1 − e− t
τ

(3)
where EE
.
VO2 represents the relative end-exercise
.
VO2 during the on-transient kinetics
phase. During exercise (on-kinetics), O2 deﬁcit,
.
VO2 demand and τ were estimated [53].
The acute recovery period in this study reﬂected the 10 min following the submaximal
exercise protocol. Within this period, time to 50% (T50%) was determined by the recording
of consistent breaths under 50% of the
.
VO2max value reached [19].
.
VO2max was determined
from the highest
.
VO2 values recorded over a 15-breath rolling average [54].
2.5.4. Demanding Aerobic Session—Visit 2 and 4
Visit 2 and 4 involved 65 min of exercise, with an overall target exercise intensity of
~75%
.
VO2max, designed to elicit muscular oxidative stress [45]. Participants completed
a 5 min warm-up at a speed corresponding to LT1. Exercise intensity then increased to
speeds that corresponded with 60% of the difference between LT1 and LT2 (∆LT1-LT2)
for 50 min, before completing a maximum of 5 × 1 min intervals at a speed 10% above
LT2, interspersed with 1 min active recovery at 60% ∆LT1-LT2. B[La], HR and RPE were
measured at rest, and at 10, 30 and 48 min, and following the last interval. Exercise intensity
was consistent between visit 2 and 4. Additionally, as a means to quantify whether the
nutritional intervention inﬂuenced plasma HT (as the main polyphenol in OliP), resting
whole blood measures were undertaken prior to both visit 2 and 4 (as part of a larger study
reported elsewhere [45]). For this, whole blood samples were collected into 4 mL Vacuette™
K2EDTA tubes (Greiner Bio-One GmbH, Kremsmunster, Austria), centrifuged at 2000 rcf
for 10 min, with extracted plasma stored at −80 ◦C until analysis for HT. Plasma HT was
assessed using a liquid–liquid extraction method following acidic hydrolysis, with gas
chromatography–mass spectrometry (GC-MS) analysis (Agilent 7820A GC, Santa Clara,
CA, USA [45]).
2.6. Nutritional Intervention
Nutritional supplementation was distributed in a double-blinded manner to partici-
pants upon completion of visit 3. Product dose and timeframe were based on commercial
product supply and company recommendations to consume 1 box (32 jars) of OliP as an
acute intervention period. Therefore, participants were provided 32 jars in identically
Nutrients 2023, 15, 421
7 of 20
labelled boxes and requested to consume 2 jars per day (56 mL total) separated by ~6 h
between meals across 16-days. Each jar contained ~28 mL of either OliP (sweetened version,
Batch 14, Fattoria La Vialla, Castiglion Fibocchi, Arezzo, Italy [see Supplementary Mate-
rials, Table S2 for independent product analysis]) or taste- and appearance-matched PL
(equal ratio of: prune juice [Sunsweet California Prune Juice, Tesco, Welwyn Garden City,
UK], diet cola [Tesco Cola, Tesco, Welwyn Garden City, UK] and tonic water [low-calorie
Indian tonic water, Tesco, Welwyn Garden City, UK]). To monitor adherence, participants
returned all jars at the end of the trial, including any remaining full jars for conﬁrmation of
intervention adherence.
2.7. Dietary and Exercise Activity Analysis
Dietary analysis occurred via Nutritics Professional Dietary Analysis software (Nu-
tritics Ltd., Co., Dublin, Ireland). Three-day dietary intake was analyzed prior to each
laboratory visit to ensure study guideline protocols were adhered to (Table 2). Estimation of
dietary HT intake was also assessed (excluding supplementation) using the US Department
of Agriculture and the Phenol-Explorer databases. Exercise data allowed for assessment
of training load, monotony and strain as previously reported [45,55] (Table 3) to quantify
relative consistency between cohorts.
Table 2. Energy and macronutrient intake for both groups within the 3-day control period prior to
visit 2 (pre-intervention) and 4 (post-intervention).
Variable
Time
OliP
PL
Kcal·d−1
Pre
2134.9 ± 139.7
2149.6 ± 112.3
Post
2172.1 ± 135.5
2456.8 ± 151.2
CHO (g·d−1)
Pre
232.9 ± 17.4
259.7 ± 15.9
Post
240.0 ± 16.1
273.8 ± 22.8
CHOrelative (g·kg−1·d−1)
Pre
3.2 ± 0.3
3.9 ± 0.2
Post
3.3 ± 0.2
4.1 ± 0.3
FAT (g·d−1)
Pre
85.9 ± 6.2
76.7 ± 4.8
Post
87.0 ± 6.4
97.9 ± 6.2
FATrelative (g·kg−1·d−1)
Pre
1.2 ± 0.1
1.2 ± 0.1
Post
1.1 ± 0.1
1.5 ± 0.1
PRO (g·d−1)
Pre
103.0 ± 8.6
104.2 ± 7.6
Post
103.4 ± 7.7
115.6 ± 9.1
PROrelative (g·kg−1·d−1)
Pre
1.4 ± 0.1
1.5 ± 0.1
Post
1.4 ± 0.1
1.7 ± 0.2
No statistical differences were reported between groups (p > 0.05). Units: Kcal·d−1 = kilocalories per day;
g· d−1 = grams per day; g·kg−1·d−1 = grams per kilogram body mass per day.
2.8. Statistical Analysis
Statistical analysis was performed using SPSS (V.28, IBM Corporation, Armonk, New
York, USA), with statistical signiﬁcance determined as p ≤ 0.05. All data were assessed for
homogeneity using Levene’s test and normality through a Shapiro-Wilk’s test [56]. A two-
way repeated measures ANOVA was used for the main analysis with Greenhouse-Geisser
corrections applied if sphericity could not be assumed. For plasma HT analysis, a mixed
design ANOVA was also undertaken. Bonferroni post-hoc comparisons were employed
where applicable, with effect sizes (partial eta squared ηp2) also reported (small = 0.02,
medium = 0.13, large = 0.26). An independent samples t-test was also adopted to compare
relevant data between groups (i.e., participant characteristics, dietary intake and training
records), whereby Cohen’s d effect sizes were utilized (trivial ≤ 0.19, small = 0.20–0.49,
medium = 0.50–0.70, large ≥ 0.80). Data are presented as mean ± SE.
Nutrients 2023, 15, 421
8 of 20
Table 3. Mean habitual exercise activity for both groups within the 3-day control period prior to visit
2 (pre-intervention) and 4 (post-intervention), as well as collated mean training parameters across the
intervention period.
Control Period (3-Days) Prior to Laboratory Visits
Variable
Time
OliP
PL
Training load (AU)
Pre
641 ± 106
646 ± 116
Post
722 ± 80
802 ± 150
Training monotony
(AU)
Pre
0.9 ± 0.1
1.0 ± 0.1
Post
1.0 ± 0.1
1.2 ± 0.1
Training strain (AU)
Pre
730 ± 182
583 ± 118
Post
753 ± 143
1112 ± 272
Across the 16-day intervention
Exercise sessions completed
13 ± 1
15 ± 1
Session duration (min)
58.6 ± 4.2
67.3 ± 4.9
HR (b·min−1)
135 ± 4
140 ± 4
Session perceived exertion
5.2 ± 0.3
4.8 ± 0.3
AU = arbitrary units. No statistical differences were reported between groups (p > 0.05).
3. Results
3.1. Dietary Intake, Supplement Adherence, and Exercise Monitoring
No signiﬁcant differences were reported within or between groups in the 3-day period
leading into exercise testing for energy (kcal·d−1), carbohydrate (CHO), fat (FAT), and
protein (PRO) intake (Table 2). HT intake during the 3-day dietary control periods prior to
each visit demonstrated no differences within or between groups (p > 0.05). Mean intake of
dietary HT during control periods prior to visit 2 and 4 were 0.06 ± 0.11 and 0.04 ± 0.10 mg
for OliP, and 0.08 ± 0.13 and 0.13 ± 0.16 mg for PL respectively. Estimation of general
dietary HT throughout the intervention period (excluding OliP intake) indicated a mean
total intake of 0.14 ± 0.07 mg·kg−1·d−1 for OliP compared to 0.18 ± 0.11 mg·kg−1·d−1 for
PL (p > 0.05) and was considered low. Within groups, supplementation adherence rates
were 99.0% OliP and 98.1% PL, with no between group differences reported (p > 0.05).
No differences were reported within or between groups during the 3-day control
period for training load, monotony, or strain (p > 0.05, Table 3). Additionally, no differ-
ences were reported between groups for habitual exercise activity throughout the 16-day
intervention (p > 0.05; [45]).
3.2. Demanding Aerobic Session—Visit 2 and 4
No differences within or between groups were found for the aerobic test (p > 0.05,
Table 4) demonstrating relative consistency. Overall, mean target exercise intensity of
~75%
.
VO2max was achieved and sustained in both exercise sessions (76.08 ± 1.04 and
75.42 ± 0.98%, visit 2 and 4, respectively). Exercise intensity was consistent between
groups for visit 2 and 4 in the OliP (11.4 ± 1.7 km·h−1) and PL group (11.5 ± 1.8 km·h−1;
both p > 0.05). Plasma HT was not detected at baseline (visit 2, pre-supplementation) or
following PL, but signiﬁcantly increased from 0.0 ± 0.0 to 6.3 ± 1.6 ng·mL−1 following
OliP (F = 14.28, p = 0.001, ηp2 = 0.43).
3.3. Submaximal Exercise—Visit 3 and 5
Onset of exercise: For time constant (τ), there was a signiﬁcant effect for time (F = 5.23,
p = 0.031, ηp2 = 0.17) and group (F = 4.44, p = 0.045, ηp2 = 0.15). A signiﬁcant difference
between groups pre-intervention (visit 3) was found (F = 4.36, p = 0.047, ηp2 = 0.15). A
signiﬁcant reduction from visit 3 and 5 was found in τ within OliP (F = 9.51, p = 0.005,
ηp2 = 0.28, Figure 2, Table 5A) only. No differences were found for the PL group (p > 0.05).
Nutrients 2023, 15, 421
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Table 4. Physiological responses for both groups during the demanding aerobic session at visit 2
(pre-intervention) and 4 (post-intervention).
Variable
OliP
PL
Pre
Post
Pre
Post
.
VO2 (mL·kg−1·min−1)
36.6 ± 1.5
36.7 ± 1.5
37.7 ± 1.6
37.4 ± 1.4
% of baseline
.
VO2max (%)
76.6 ± 1.5
76.7 ± 1.2
75.0 ± 1.8
74.6 ± 1.8
.
VO2 (L·min−1)
2.70 ± 0.14
2.70 ± 0.15
2.56 ± 0.17
2.54 ± 0.15
.
VCO2 (L·min−1)
2.49 ± 0.14
2.49 ± 0.13
2.36 ± 0.16
2.34 ± 0.15
.
VE (L·min−1)
85.12 ± 4.59
84.87 ± 4.68
80.99 ± 4.66
80.49 ± 4.11
.
VE/
.
VO2
29.44 ± 0.46
29.33 ± 0.48
29.82 ± 1.01
30.01 ± 0.98
.
VE /
.
VCO2
31.88 ± 0.45
31.75 ± 0.46
32.34 ± 1.11
32.55 ± 1.11
RER
0.92 ± 0.01
0.92 ± 0.01
0.92 ± 0.01
0.92 ± 0.01
Economy (mL·kg−1·km−1)
193.6 ± 3.5
194.0 ± 3.4
198.4 ± 4.7
197.2 ± 4.0
B[La] (mmol·L−1)
1.32 ± 0.11
1.31 ± 0.10
1.33 ± 0.11
1.33 ± 0.09
.
VO2max = maximal oxygen uptake;
.
VO2 = volume of oxygen;
.
VCO2 = volume of carbon dioxide;
.
VE = minute
ventilation; RER = respiratory exchange ratio; B[La] = blood lactate concentration. No differences reported within
or between groups (p > 0.05).
 
ab e
.
ysio ogica
espo ses o bo
g oups
u i g
e
e
a
i g ae obic sessio
a
isi
(pre-intervention) and 4 (post-intervention). 
Variable 
OliP 
PL 
Pre 
Post 
Pre 
Post 
V̇ O2 (mL·kg−1·min−1) 
36.6 ± 1.5 
36.7 ± 1.5 
37.7 ± 1.6 
37.4 ± 1.4 
% of baseline V̇ O2max (%) 
76.6 ± 1.5 
76.7 ± 1.2 
75.0 ± 1.8 
74.6 ± 1.8 
V̇ O2 (L·min−1) 
2.70 ± 0.14 
2.70 ± 0.15 
2.56 ± 0.17 
2.54 ± 0.15 
V̇ CO2 (L·min−1) 
2.49 ± 0.14 
2.49 ± 0.13 
2.36 ± 0.16 
2.34 ± 0.15 
V̇ E (L·min−1) 
85.12 ± 4.59 
84.87 ± 4.68 
80.99 ± 4.66 
80.49 ± 4.11 
V̇ E/V̇ O2 
29.44 ± 0.46 
29.33 ± 0.48 
29.82 ± 1.01 
30.01 ± 0.98 
V̇ E /V̇ CO2 
31.88 ± 0.45 
31.75 ± 0.46 
32.34 ± 1.11 
32.55 ± 1.11 
RER 
0.92 ± 0.01 
0.92 ± 0.01 
0.92 ± 0.01 
0.92 ± 0.01 
Economy (mL·kg−1·km−1) 
193.6 ± 3.5 
194.0 ± 3.4 
198.4 ± 4.7 
197.2 ± 4.0 
B[La] (mmol·L−1) 
1.32 ± 0.11 
1.31 ± 0.10 
1.33 ± 0.11 
1.33 ± 0.09 
V̇ O2max = maximal oxygen uptake; V̇ O2 = volume of oxygen; V̇ CO2 = volume of carbon dioxide; V̇ E = 
minute ventilation; RER = respiratory exchange ratio; B[La] = blood lactate concentration. No differ-
ences reported within or between groups (p > 0.05). 
3.3. Submaximal Exercise—Visit 3 and 5 
Onset of exercise: For time constant (τ), there was a significant effect for time (F = 
5.23, p = 0.031, ηp2 = 0.17) and group (F = 4.44, p = 0.045, ηp2 = 0.15). A significant difference 
between groups pre-intervention (visit 3) was found (F = 4.36, p = 0.047, ηp2 = 0.15). A sig-
nificant reduction from visit 3 and 5 was found in τ within OliP (F = 9.51, p = 0.005, ηp2 = 
0.28, Figure 2, Table 5A) only. No differences were found for the PL group (p > 0.05). 
 
Figure 2. Time constant (τ) at the onset of exercise pre- and post-intervention for OliP and PL 
groups. * denotes significant difference between groups pre intervention (p = 0.047), ** denotes sig-
nificant difference between time points for OliP (p = 0.005).Lactate threshold 1 (LT1): Respiratory 
parameters, exercise economy, B[La] and RPE are shown in Table 5A pre- to post-intervention for 
both OliP and PL. There was a significant interaction effect for relative V̇ O2 (time x group: F = 4.66, 
p = 0.039, ηp2 = 0.16, Figure 3A), where a reduction in relative V̇ O2 was found in the OliP group 
between visit 3 and 5 (F = 7.09, p = 0.013, ηp2 = 0.22). Whilst no differences were found post interven-
tion between OliP and PL, when expressed as relative change, OliP demonstrated a −2.7 ± 1.2% 
reduction in V̇ O2 compared with the PL group at LT1 intensity (−0.7 ± 1.0%; t = 2.13, p = 0.043, d = 
0.82, 95% confidence interval [CI] range 0.05 to 1.64). This corresponded with a significant reduction 
in the % of V̇ O2max from baseline (73.7 ± 1.8% in visit 3 to 71.2 ±1.6% in visit 5) (F = 7.72, p = 0.01, ηp2 
= 0.24, Figure 3B) for OliP only. No differences were reported in the PL group (p > 0.05), or post 
 
✱✱
✱
Figure 2. Time constant (τ) at the onset of exercise pre- and post-intervention for OliP and PL groups.
* denotes signiﬁcant difference between groups pre intervention (p = 0.047), ** denotes signiﬁcant
difference between time points for OliP (p = 0.005).
Lactate threshold 1 (LT1): Respiratory parameters, exercise economy, B[La] and RPE
are shown in Table 5A pre- to post-intervention for both OliP and PL. There was a signiﬁcant
interaction effect for relative
.
VO2 (time x group: F = 4.66, p = 0.039, ηp2 = 0.16, Figure 3A),
where a reduction in relative
.
VO2 was found in the OliP group between visit 3 and 5 (F =
7.09, p = 0.013, ηp2 = 0.22). Whilst no differences were found post intervention between OliP
and PL, when expressed as relative change, OliP demonstrated a −2.7 ± 1.2% reduction
in
.
VO2 compared with the PL group at LT1 intensity (−0.7 ± 1.0%; t = 2.13, p = 0.043, d =
0.82, 95% conﬁdence interval [CI] range 0.05 to 1.64). This corresponded with a signiﬁcant
reduction in the % of
.
VO2max from baseline (73.7 ± 1.8% in visit 3 to 71.2 ±1.6% in visit 5)
(F = 7.72, p = 0.01, ηp2 = 0.24, Figure 3B) for OliP only. No differences were reported in the
PL group (p > 0.05), or post intervention in comparison to OliP. A signiﬁcant interaction
effect was also observed for running economy (time x group: F = 5.22, p = 0.031, ηp2 = 0.17,
Figure 3C), with a signiﬁcant improvement demonstrated between visit 3 and 5 for OliP
only (F = 6.82, p = 0.015, ηp2 = 0.21, 95% CI range 189.80 to 207.11). Finally, it was also noted
that when expressed as relative change, there was a pre- to post-intervention reduction in
.
VCO2 within OliP (−1.6 ± 0.9%) compared to PL (+1.5 ± 0.9%; t = 2.33, p = 0.028, d = 0.90).
Nutrients 2023, 15, 421
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Table 5. Respiratory, exercise economy, perceived exertion, and blood lactate parameters at the onset
of exercise and lactate threshold (A), and lactate turnpoint (B) at visit 3 (pre-intervention) and 5
(post-intervention) interspersed with 16 consecutive days of either OliP or PL.
(A)
OliP
PL
Onset of Exercise
Pre
Post
Pre
Post
.
VO2 at baseline
(mL·kg−1·min−1)
8.48 ± 1.13
6.88 ± 0.55
6.43 ± 0.81
6.25 ± 0.60
.
VO2 demand at 60 s (L)
1.69 ± 0.15
1.74 ± 0.12
1.80 ± 0.16
1.78 ± 0.14
.
VO2 demand at 120 s (L)
3.39 ± 0.29
3.47 ± 0.23
3.60 ± 0.31
3.55 ± 0.28
.
VO2 demand at 180 s (L)
4.80 ± 0.43
4.94 ± 0.32
5.08 ± 0.43
5.03 ± 0.40
O2 deﬁcit (L)
0.97 ± 0.08
0.85 ± 0.07
0.84 ± 0.07
0.81 ± 0.07
τ (s)
40.5 ± 4.6
30.5 ± 1.5 *
29.2 ± 1.9
28.1 ± 1.1
Mean
.
VO2 in the last 60 s
(mL·kg−1·min−1)
30.7 ± 1.5
30.0 ± 1.5
30.3 ± 2.2
31.1 ± 1.6
Lactate threshold (LT1)
%
.
VO2max of baseline (%)
73.0 ± 1.8
70.9 ± 1.6 *
68.7 ± 1.4
69.2 ± 1.6
.
VO2 (L·min−1)
2.56 ± 0.13
2.50 ± 0.13 *
2.45 ± 0.15
2.46 ± 0.13
.
VCO2 (L·min−1)
2.30 ± 0.12
2.26 ± 0.12
2.16 ± 0.15
2.19 ± 0.13
.
VE (L·min−1)
71.81 ± 3.55
71.36 ± 3.74
67.62 ± 4.09
68.56 ± 4.19
.
VE/
.
VO2
26.17 ± 0.36
26.65 ± 0.42
25.83 ± 0.78
25.94 ± 0.88
.
VE/
.
VCO2
29.22 ± 0.45
29.41 ± 0.44
29.30 ± 0.91
29.21 ± 1.04
RER
0.90 ± 0.01
0.91 ± 0.01
0.88 ± 0.01
0.89 ± 0.01
Economy (mL·kg−1·km−1)
201.3 ± 3.6
195.6 ± 4.0 *
199.4 ± 5.1
201.2 ± 5.9
RPE
2.9 ± 0.3
2.7 ± 0.3
3.2 ± 0.5
3.3 ± 0.1
B[La] (mmol·L−1)
1.32 ± 0.11
1.31 ± 0.10
1.33 ± 0.11
1.33 ± 0.09
(B)
OliP
PL
Lactate turnpoint (LT2)
Pre
Post
Pre
Post
%
.
VO2max (%)
84.1 ± 1.8
83.5 ± 1.4
81.2 ± 2.0
82.8 ± 2.1
.
VO2 (L·min−1)
2.96 ± 0.16
2.95 ± 0.17
2.91 ± 0.21
2.96 ± 0.16
.
VCO2 (L·min−1)
2.81 ± 0.15
2.81 ± 0.15
2.73 ± 0.20
2.79 ± 0.19
.
VE (L·min−1)
92.73 ± 4.87
92.28 ± 5.16
88.00 ± 5.48
89.80 ± 5.89
.
VE /
.
VO2
29.46 ± 0.50
29.41 ± 0.52
28.72 ± 0.98
28.60 ± 1.11
.
VE /
.
VCO2
31.00 ± 0.48
30.80 ± 0.47
30.69 ± 1.04
30.25 ± 1.13
RER
0.95 ± 0.01
0.95 ±0.01
0.94 ± 0.01
0.94 ± 0.01
Economy (mL·kg−1·km−1)
192.7 ± 4.5
191.1 ± 3.5
193.7 ± 4.7
197.7 ± 4.2
RPE
6.0 ± 0.34
5.4 ± 0.4 *
5.6 ± 0.4
5.4 ± 0.4
B[La] (mmol·L−1)
2.31 ± 0.12
2.18 ± 0.11
2.24 ± 0.12
2.22 ± 0.12
τ = time constant;
.
VO2max = maximal oxygen uptake;
.
VO2 = volume of oxygen;
.
VCO2 = volume of carbon dioxide;
.
VE = minute ventilation; RER = respiratory exchange ratio; RPE = rating of perceived exertion; B[La] = blood
lactate concentration. * denotes a signiﬁcant within group difference (p < 0.05).
 
intervention in comparison to OliP. A significant interaction effect was also observed for running 
economy (time x group: F = 5.22, p = 0.031, ηp2 = 0.17, Figure 3C), with a significant improvement 
demonstrated between visit 3 and 5 for OliP only (F = 6.82, p = 0.015, ηp2 = 0.21, 95% CI range 189.80 
to 207.11). Finally, it was also noted that when expressed as relative change, there was a pre- to post-
intervention reduction in V̇ CO2 within OliP (−1.6 ± 0.9%) compared to PL (+1.5 ± 0.9%; t = 2.33, p = 
0.028, d = 0.90). 
Table 5. Respiratory, exercise economy, perceived exertion, and blood lactate parameters at the on-
set of exercise and lactate threshold (A), and lactate turnpoint (B) at visit 3 (pre-intervention) and 5 
(post-intervention) interspersed with 16 consecutive days of either OliP or PL. 
 (A)  
OliP 
PL 
Onset of Exercise 
Pre 
Post 
Pre 
Post 
V̇ O2 at baseline (mL·kg−1·min−1) 
8.48 ± 1.13 
6.88 ± 0.55 
6.43 ± 0.81 
6.25 ± 0.60 
V̇ O2 demand at 60 s (L) 
1.69 ± 0.15 
1.74 ± 0.12 
1.80 ± 0.16 
1.78 ± 0.14 
V̇ O2 demand at 120 s (L) 
3.39 ± 0.29 
3.47 ± 0.23 
3.60 ± 0.31 
3.55 ± 0.28 
V̇ O2 demand at 180 s (L) 
4.80 ± 0.43 
4.94 ± 0.32 
5.08 ± 0.43 
5.03 ± 0.40 
O2 deficit (L) 
0.97 ± 0.08  
0.85 ± 0.07  
0.84 ± 0.07 
0.81 ± 0.07 
τ (s) 
40.5 ± 4.6  
30.5 ± 1.5 * 
29.2 ± 1.9 
28.1 ± 1.1 
Mean V̇ O2 in the last 60 s 
(mL·kg−1·min−1) 
30.7 ± 1.5  
30.0 ± 1.5 
30.3 ± 2.2 
31.1 ± 1.6 
Lactate threshold (LT1) 
 
 
 
 
%V̇ O2max of baseline (%) 
73.0 ± 1.8 
70.9 ± 1.6 * 
68.7 ± 1.4 
69.2 ± 1.6 
V̇ O2 (L·min−1) 
2.56 ± 0.13 
2.50 ± 0.13 * 
2.45 ± 0.15 
2.46 ± 0.13 
V̇ CO2 (L·min−1) 
2.30 ± 0.12 
2.26 ± 0.12 
2.16 ± 0.15 
2.19 ± 0.13 
V̇ E (L·min−1) 
71.81 ± 3.55 
71.36 ± 3.74 
67.62 ± 4.09 
68.56 ± 4.19 
V̇ E /V̇ O2 
26.17 ± 0.36 
26.65 ± 0.42 
25.83 ± 0.78 
25.94 ± 0.88 
V̇ E /V̇ CO2 
29.22 ± 0.45 
29.41 ± 0.44 
29.30 ± 0.91 
29.21 ± 1.04 
RER 
0.90 ± 0.01 
0.91 ± 0.01 
0.88 ± 0.01 
0.89 ± 0.01 
Economy (mL·kg−1·km−1) 
201.3 ± 3.6  
195.6 ± 4.0 * 
199.4 ± 5.1 
201.2 ± 5.9 
RPE  
2.9 ± 0.3 
2.7 ± 0.3 
3.2 ± 0.5 
3.3 ± 0.1 
B[La] (mmol·L−1) 
1.32 ± 0.11 
1.31 ± 0.10 
1.33 ± 0.11 
1.33 ± 0.09 
(B) 
OliP 
PL 
Lactate turnpoint (LT2) 
Pre 
Post 
Pre 
Post 
%V̇ O2max (%) 
84.1 ± 1.8 
83.5 ± 1.4 
81.2 ± 2.0 
82.8 ± 2.1 
V̇ O2 (L·min−1) 
2.96 ± 0.16 
2.95 ± 0.17 
2.91 ± 0.21 
2.96 ± 0.16  
V̇ CO2 (L·min−1) 
2.81 ± 0.15 
2.81 ± 0.15 
2.73 ± 0.20 
2.79 ± 0.19 
V̇ E (L·min−1) 
92.73 ± 4.87 
92.28 ± 5.16 
88.00 ± 5.48 
89.80 ± 5.89 
V̇ E /V̇ O2 
29.46 ± 0.50 
29.41 ± 0.52 
28.72 ± 0.98 
28.60 ± 1.11 
V̇ E /V̇ CO2 
31.00 ± 0.48 
30.80 ± 0.47 
30.69 ± 1.04 
30.25 ± 1.13 
RER 
0.95 ± 0.01 
0.95 ±0.01 
0.94 ± 0.01 
0.94 ± 0.01 
Economy (mL·kg−1·km−1) 
192.7 ± 4.5 
191.1 ± 3.5 
193.7 ± 4.7 
197.7 ± 4.2 
RPE 
6.0 ± 0.34 
5.4 ± 0.4 * 
5.6 ± 0.4 
5.4 ± 0.4 
B[La] (mmol·L−1) 
2.31 ± 0.12 
2.18 ± 0.11 
2.24 ± 0.12 
2.22 ± 0.12 
τ = time constant; V̇ O2max = maximal oxygen uptake; V̇ O2 = volume of oxygen; V̇ CO2 = volume of carbon dioxide; V̇ E 
= minute ventilation; RER = respiratory exchange ratio; RPE = rating of perceived exertion; B[La] = blood lactate 
concentration. * denotes a significant within group difference (p < 0.05). 
V̇ O2
(mL·kg−1·min−1)
✱
V̇ O2max (%)
✱
Economy
(mL·kg−1·km−1)
✱
 
Figure 3. Summary respiratory and economy differences at lactate threshold (LT1) intensity pre and
post 16 consecutive days consumption of either OliP or PL for (A)
.
VO2; (B)
.
VO2max % of baseline
and (C) running economy. * denotes signiﬁcance between time points in the OliP group (p < 0.05).
Nutrients 2023, 15, 421
11 of 20
Lactate turnpoint (LT2): There was a signiﬁcant interaction reported for RPE at LT2
(time x group: F = 7.99, p = 0.009, ηp2 = 0.24), where a reduction in RPE was found in the
OliP group between visit 3 and 5 only (F = 11.01, p = 0.003, ηp2 = 0.30). No other differences
were found within or between groups at this exercise intensity (p > 0.05, Table 5B).
3.4. Recovery from Submaximal Exercise
There was a significant interaction effect for T50% in acute recovery responses (time × group:
F = 7.72, p = 0.010, ηp2 = 0.24), where post-hoc assessment indicated a reduction in T50%
for the OliP group only between visit 3 and 5 (F = 5.67, p = 0.026, ηp2 = 0.19, Figure 4). No
other changes were observed for respiratory variables assessed (Table 6).
Nutrients 2023, 15, x FOR PEER REVIEW 
11 of 20 
 
 
Figure 3. Summary respiratory and economy differences at lactate threshold (LT1) intensity pre and 
post 16 consecutive days consumption of either OliP or PL for (A) V̇ O2; (B) V̇ O2max % of baseline and 
(C) running economy. * denotes significance between time points in the OliP group (p < 0.05). 
Lactate turnpoint (LT2): There was a significant interaction reported for RPE at LT2 
(time x group: F = 7.99, p = 0.009, ηp2 = 0.24), where a reduction in RPE was found in the 
OliP group between visit 3 and 5 only (F = 11.01, p = 0.003, ηp2 = 0.30). No other differences 
were found within or between groups at this exercise intensity (p > 0.05, Table 5B). 
3.4. Recovery from Submaximal Exercise 
There was a significant interaction effect for T50% in acute recovery responses (time 
× group: F = 7.72, p = 0.010, ηp2 = 0.24), where post-hoc assessment indicated a reduction in 
T50% for the OliP group only between visit 3 and 5 (F = 5.67, p = 0.026, ηp2 = 0.19, Figure 
4). No other changes were observed for respiratory variables assessed (Table 6). 
 
Figure 4. Recovery to T50% at pre- and post-intervention time points for the OliP and PL groups. * 
denotes significance between time points in the OliP group (p = 0.026). 
Table 6. Recovery from submaximal exercise by intervention group (visit 3 and visit 5). 
Variable 
OliP 
PL 
Pre 
Post 
Pre 
Post 
EEV̇ O2 (mL·kg−1·min−1) 
44.3 ± 2.1 
43.8 ± 2.2 
46.7 ± 2.4 
47.0 ± 2.0 
%V̇ O2max (%) 
92.8 ± 1.4 
91.6 ± 1.8 
91.6 ± 7.6 
92.5 ± 5.9 
Amplitude (mL·kg−1·min−1) 
36.9 ± 1.8 
36.59 ± 2.1 
39.16 ± 2.0 
38.5 ± 2.1 
τ (s) 
51.6 ± 2.6 
52.3 ± 9.4 
47.9 ± 2.2 
49.6 ± 2.7 
T50% (s) 
55.1 ± 2.2 
50.4 ± 3.4 * 
53.9 ± 2.0 
50.6 ± 1.5 
EEV̇ O2 = End of exercise volume of oxygen; V̇ O2max = maximum oxygen uptake; τ = time constant; 
T50% = 50% of end of exercise volume of oxygen. * denotes a significant within group difference (p 
= 0.026). 
3.5. Time to Exhaustion and V̇ O2max 
A significant effect was found for time during TTE (F = 11.49, p = 0.002, ηp2 = 0.32) 
which increased post-intervention for both OliP (+4.1 ± 1.8%) and PL (+5.8 ± 2.6%), with 
no differences reported between groups for final run speed (12.6 ± 0.5 km∙h−1 for OliP, 12.9 
± 0.7 km∙h−1 for PL, p > 0.05, Table 7). A significant interaction effect was reported for 
V̇ O2max (time x group: F = 16.79, p = 0.033, ηp2 = 0.17), where V̇ O2max increased post-inter-
vention for PL (F = 7.17, p = 0.013, ηp2 = 0.22, 95% CI range 44.37 to 55.24), but not OliP (F 
= 0.16, p = 0.693, ηp2 = 0.01, 95% CI range 347.39 to 414.41). A significant interaction effect 
was reported for V̇ CO2max (time x group: F = 18.69, p = 0.018, ηp2 = 0.20), with a post-inter-
vention increase in V̇ CO2max reported for the PL (F = 13.77, p = 0.001, ηp2 = 0.36, 95% CI 
✱
Figure 4. Recovery to T50% at pre- and post-intervention time points for the OliP and PL groups.
* denotes signiﬁcance between time points in the OliP group (p = 0.026).
Table 6. Recovery from submaximal exercise by intervention group (visit 3 and visit 5).
Variable
OliP
PL
Pre
Post
Pre
Post
EE
.
VO2 (mL·kg−1·min−1)
44.3 ± 2.1
43.8 ± 2.2
46.7 ± 2.4
47.0 ± 2.0
%
.
VO2max (%)
92.8 ± 1.4
91.6 ± 1.8
91.6 ± 7.6
92.5 ± 5.9
Amplitude (mL·kg−1·min−1)
36.9 ± 1.8
36.59 ± 2.1
39.16 ± 2.0
38.5 ± 2.1
τ (s)
51.6 ± 2.6
52.3 ± 9.4
47.9 ± 2.2
49.6 ± 2.7
T50% (s)
55.1 ± 2.2
50.4 ± 3.4 *
53.9 ± 2.0
50.6 ± 1.5
EE
.
VO2 = End of exercise volume of oxygen;
.
VO2max = maximum oxygen uptake; τ = time constant; T50% = 50%
of end of exercise volume of oxygen. * denotes a signiﬁcant within group difference (p = 0.026).
3.5. Time to Exhaustion and
.
VO2max
A signiﬁcant effect was found for time during TTE (F = 11.49, p = 0.002, ηp2 = 0.32)
which increased post-intervention for both OliP (+4.1 ± 1.8%) and PL (+5.8 ± 2.6%), with
no differences reported between groups for ﬁnal run speed (12.6 ± 0.5 km·h−1 for OliP,
12.9 ± 0.7 km·h−1 for PL, p > 0.05, Table 7). A signiﬁcant interaction effect was reported
for
.
VO2max (time x group: F = 16.79, p = 0.033, ηp2 = 0.17), where
.
VO2max increased post-
intervention for PL (F = 7.17, p = 0.013, ηp2 = 0.22, 95% CI range 44.37 to 55.24), but not
OliP (F = 0.16, p = 0.693, ηp2 = 0.01, 95% CI range 347.39 to 414.41). A signiﬁcant interaction
effect was reported for
.
VCO2max (time x group: F = 18.69, p = 0.018, ηp2 = 0.20), with a
post-intervention increase in
.
VCO2max reported for the PL (F = 13.77, p = 0.001, ηp2 = 0.36,
95% CI range 47.56 to 60.76) but not the OliP group (F = 0.61, p = 0.444, ηp2 = 0.24, 95% CI
range 47.74 to 59.54).
Nutrients 2023, 15, 421
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Table 7. Time to exhaustion, respiratory, exercise economy and perceived exertion parameters during
maximal intensity exercise at visit 3 (pre-intervention) and 5 (post-intervention) for OliP and PL groups.
Variable
OliP
PL
Pre
Post
Pre
Post
TTE (s)
378.7 ± 13.5
393.1 ± 13.4 *
357.0 ± 15.7
377.5 ± 18.3 *
.
VO2max (mL·kg−1·min−1)
48.2 ± 2.6
48.0 ± 2.5
48.8 ± 2.6
50.8 ± 2.3 *
.
VCO2max (mL·kg−1·min−1)
53.4 ± 3.0
53.9 ± 2.8
52.7 ± 3.2
55.6 ± 3.2 *
.
VE (L·min−1)
141.29 ± 8.24
142.40 ± 8.86
136.76 ± 11.21
142.23 ± 10.70
hRER
1.13 ± 0.01
1.14 ± 0.02
1.11 ± 0.02
1.13 ± 0.02
Speed at
.
VO2max (km·h−1)
14.7 ± 0.7
14.9 ± 0.7
15.0 ± 0.9
15.4 ± 0.8
RPE
9.8 ± 0.1
9.6 ± 0.2
9.6 ± 0.1
9.8 ± 0.1
TTE = time to exhaustion;
.
VO2max = maximal oxygen uptake;
.
VO2 = volume of oxygen;
.
VCO2 = volume of carbon
dioxide;
.
VE = minute ventilation; RER = respiratory exchange ratio; RPE = rating of perceived exertion. * denotes
a signiﬁcant within group difference (p ≤ 0.031).
4. Discussion
To the authors’ knowledge, this is the ﬁrst study to undertake research focusing on
OliP in an exercise domain and aligns with concurrent research pertinent to olive-derived
phytonutrients [45]. The key ﬁndings from this study demonstrate that 16 consecutive
days consumption of OliP resulted in positive effects on several key markers of running
performance. Of particular interest, OliP consumption signiﬁcantly improved respiratory
parameters at the onset of exercise within condition (i.e., τ), and oxygen consumption and
running economy at LT1 (particularly when expressed as relative change in comparison
to PL). Whilst respiratory parameters at LT2 were largely unaffected by OliP, perceived
exertion was improved with the phytocomplex beverage. Acute recovery (T50%) following
incremental exercise was also notably improved with OliP. Whilst maximal effort and TTE
measures were not different between OliP and PL, an elevated
.
VCO2max was reported
for PL only. Furthermore, it was noted that both groups improved TTE following the
intervention. Importantly, no adverse effects were reported throughout the intervention.
Regarding methodological approaches to the demanding aerobic session, steady-
state moderate intensity exercise (60–70%
.
VO2max) for 30–60 min followed by arduous
(90%
.
VO2max) [57] or performance efforts [58] have been shown to provoke a heightened
oxidative stress response and elicit peripheral fatigue. Accordingly, the demanding aerobic
sessions employed in the current study resulted in an intensity of ~75%
.
VO2max, with no
differences within or between groups. It can therefore be assumed that an equal degree
of physiological strain was achieved between cohorts prior to the main performance tests.
As dietary and exercise habits were maintained across the intervention, it is feasible that
physiological adaptations observed, may therefore be partly attributed to the phenolic
compounds within OliP. As a naturally derived phytocomplex, OliP is notably rich in HT,
which is a key polyphenol of interest and may support endogenous antioxidant mechanisms
pertinent to mitochondrial respiratory capacity and/or efﬁciency, such as upregulation of
PGC-1α [28,59–62].
Consumption of OliP may therefore be of relevance to individuals who engage in
regular aerobic exercise, considering the negligible dietary HT content in both the pre-visit
control period and habitual diet assessments for both cohorts. Plasma HT concentrations
were not detected at baseline (pre-supplementation), or post PL, but were signiﬁcantly
elevated in response to the OliP intervention. Therefore, any impact on aerobic exercise
may be associated with increased systemic HT concentrations, or gut-derived metabolites.
At present, however, there is a paucity of scientiﬁc research surrounding HT and exercise
performance. Additionally, there does not appear to be any existing research evidencing
the effects of HT on aerobic running performance in humans. Plant-based polyphenols
have peaked scientiﬁc interest in recent years [29,63], in particular HT, due to its potential
to impact multiple physiological pathways. In an exercise domain, recent animal studies
Nutrients 2023, 15, 421
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have demonstrated the ability of HT to enhance endurance capacity [59], prevent exercise
induced fatigue, muscle damage and immunosuppression [64,65] and improve mitochon-
drial function in both trained and sedentary rodents [65]. However, these ﬁndings need
to be corroborated in human models as well as within an exercise domain to ascertain the
efﬁcacy of HT-rich supplements.
It is also important to outline the current debate surrounding the efﬁcacy of antiox-
idant and polyphenol supplementation as an exercise or training aid. Adaptations from
exercise are dependent, at least partially, on individual oxidative stress responses [66]. One
perspective highlights the potential inhibition of natural training adaptations through lim-
iting the upregulation of endogenous antioxidant enzymes, and therefore diminishing the
hormetic response to moderate exercise [13]. However, the counterargument highlights that
the subsequent reduction in oxidative stress following antioxidant and/or polyphenol sup-
plementation may positively inﬂuence recovery kinetics, development in contractile force,
calcium handling, and therefore the ability to exercise and/or recover more ‘economically’.
This may facilitate adaptations to exercise training and/or athletic performance [17].
Findings from this study demonstrated a ~17% improvement in τ at the onset of
exercise for OliP. τ reﬂects the speed at which the steady-state is achieved [53], and in
turn the size of the O2 deﬁcit [67]. However, these results were only signiﬁcant within
condition and should therefore be interpreted with caution. In addition, it was noted that
non-signiﬁcant differences were observed between conditions prior to the nutritional inter-
vention based on random participant allocation, which may in part impact the observed
ﬁndings. Contrary to these ﬁndings, Breese et al. [68] reported no differences in
.
VO2 phase
II time constant, from unloaded to moderate exercise after 6-days supplementation with
beetroot juice (BTJ; ~8 mmol nitrate (NO3−)). Although mitochondrial respiratory capacity
was not assessed, it is known that the speed of the O2 uptake response during the onset of
moderate exercise intensity is associated with the respiratory capacity of mitochondrial
complex II and the capacity of the mitochondrial electron transport system [69,70]. As
HT has been shown to improve the expression of mitochondrial complex I/II/IV, this is
of particular interest in an exercise domain as complex I is recognized to be the primary
complex for the electron transport chain [71]. Moreover, HT has been reported to promote
the congregation of complex I (CI) into supercomplexes (SCs) [65], therefore decreasing
the diffusion distance for transfer of electrons between complexes, and improving the
efﬁciency of the mitochondrial electron transfer between complexes [59,72]. More research
is required to ascertain the above stated mechanisms in humans, particularly in relation to
OliP consumption.
Consumption of OliP in the dose provided also resulted a signiﬁcant decrease (−2.7%)
in
.
VO2 consumption at LT1 compared with PL. This aligns with existing research into
both high [73]- and low [74]-dose BTJ supplementation whereby a ~5% reduction
.
VO2
consumption was reported with no changes in
.
VE, RER or HR [74]. This modest change
could be partially attributed to the increase in mitochondrial function and increased ex-
pression of PGC-1α following supplementation of OliP. In vitro, HT administration has
been shown to upregulate nuclear respiratory factors 1 and 2, mitochondrial transcription
factor A, and peroxisome proliferator active receptor γ (PPAR γ) in response to increased
phosphorylation of adenosine monophosphate kinase (AMPK) [61]. The role HT may play
in enhancing mitochondrial respiratory capacity could also provide a rationale for the
reduced oxygen consumption observed during sub-maximal exercise at low to moderate
intensities (LT1). In vitro, HT has been shown to improve mitochondrial biogenesis, O2
and fatty acid utilization in adipocyte cells [61,75,76]. Although not measured in this study,
this may support the proposed beneﬁts of OliP in a submaximal exercise domain, however,
more research is required in humans to conﬁrm such mechanisms. It is also viable that
other phenolic compounds [38] (i.e., oleuropein aglycone) and HT derivatives (i.e., HT
glucosides) found in OliP may also support antioxidant pathways that may inﬂuence
aerobic performance [59,77]. Indeed, olive-derived phenolic compounds are not entirely
absorbed during digestion and are extensively transformed into different metabolites by
Nutrients 2023, 15, 421
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the gut microbiota [78]. For instance, whilst oleuropein transformation by gut bacteria can
increase HT yield [79], HT is further transformed into homovanillin derivatives [80,81] and
glutathione conjugates [79] which may have pertinent antioxidant properties [82]. These
metabolites may exert further physiological effects [83] potentially explaining findings from
the current study. Furthermore, HT-derived metabolite variability and quantity are also de-
pendent on the phenolic composition of the product consumed [81]. Such complexities should
also be considered when determining the physiological impact of combined polyphenols.
A relevant parameter of aerobic performance is the efﬁciency of movement, i.e., ex-
ercise economy [84]. This reﬂects the amount of O2 required to generate a constant sub-
maximal running speed and therefore, is directly associated with the efﬁciency of aerobic
fuel metabolism and the sparing of glycogen reserves [85]. Mitochondria are crucial for
aerobic energy generation in exercise [86]. Improvement in mitochondrial respiratory
capacity and functional efﬁciency following HT supplementation in animal studies has
been established [87] and is associated with the constitution of supramolecular entities, the
mitochondrial SCs, including respiratory complex I, III, and IV [88]. Administration of HT
for 10-weeks in rodents (20 vs. 300 mg·kg−1·d−1) and exercise (up to 65 min a day at 75%
of maximal velocity) compared to exercise alone improved mitochondrial function and
antioxidant capacity induced by exercise [65]. However, when the HT dose was increased
to 300 mg·kg−1·d−1, pro-oxidant effects were evident [65], which appeared to negatively
inﬂuence SCs assembly, aligning with existing published literature [64]. Collectively, these
results indicate that whilst exercise induces the formation of mitochondrial SCs [89], low-
dose HT consumption may support or enhance this process [65] whilst a high dose of
HT may provoke pro-oxidant mechanisms, disrupting the mitochondria and potentially
limiting or diminishing SC adaptation [64]. In the current study, a relatively low HT dose
was employed as part of the olive-derived phytocomplex (~0.8 mg·kg−1·d−1) in healthy
volunteers. Whilst mitochondrial function was not directly assessed, it is feasible that
HT and related gut-derived phenolic metabolites may have supported SC assembly and
facilitated improved oxygen cost responses observed at the onset of exercise and during
low to moderate exercise (LT1). Furthermore, the low HT dose employed in the current
study may also explain why exercise performance (TTE) was not signiﬁcantly different
between cohorts in line with previous research [64].
Despite OliP presenting no signiﬁcant impact on respiratory mechanisms at LT2, a
poignant ﬁnding was the observed signiﬁcant reduction in RPE at this intensity. Mecha-
nisms for this are unclear, however it is feasible that there may be a link to a reduction in
brain oxygenation that is present during intensive exercise and directly associated with
an increase of fatigue (subjectively quantiﬁed as perceived exertion) [90]. Alternatively,
mechanisms potentially occurring at a mitochondrial level and the effect upon SCI and
SCII, may indicate that beneﬁcial responses to OliP are more likely to be present at lower
intensities only. Further research is required to accurately ascertain potential mechanisms
involved in subjective measures associated with exercise.
Similarly, recovery was largely unaffected based upon off-kinetic modeling; however,
current ﬁndings did present a −9.4% decrease in T50% for OliP compared with a −5.6%
decrease in PL, during the initial recovery period from sub-maximal exercise. This in itself
warrants further investigation considering that previous ﬁndings utilizing a similar exercise
intensity (70% maximum aerobic power) did not ﬁnd a beneﬁt to
.
VO2 half-recovery time
following the supplementation of mixed polyphenols (250 mg Vinitrox™ for 7-days [19]).
In the current study it is feasible that the HT content in OliP (and related gut-dervied
metabolites) may be inﬂuencing recovery indirectly, and may therefore have applications
following repeated bouts of exercise. However, results should be interpreted with caution
and further research should be undertaken to corroborate ﬁndings. Finally, although
improvements in TTE were evident in both groups (+4.1% OliP and +5.8% PL), the overall
change in exercise performance was not different between OliP and PL. In the current
study, exercise performance was based upon physical tolerance to sustained near-maximal
exercise. Based upon ﬁndings at LT1 intensity, it could be prudent to assess whether OliP
Nutrients 2023, 15, 421
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is more effective when determining performance employing other measures such as an
extended time trial (i.e., 5 km run time) or total work completed in a ﬁxed time period as
opposed to an acute near-maximal TTE bout.
Study Limitations and Future Directions
It is important to note that there were several limitations to the current study. Firstly,
improvements were found in speciﬁc, but not all parameters assessed. As example, change
in time constant at the onset of exercise was noted within-group only for OliP and therefore
should be interpreted with caution. Likewise, during acute recovery, whilst improvements
were observed for T50%, other parameters using respiratory off-kinetics were not deemed
signiﬁcant, and again results should be interpreted carefully. However, where main in-
teraction effects were identiﬁed (including relative changes in oxygen consumption and
running economy at LT1 compared with PL) important adaptations following the inclusion
of dietary OliP may be evident. It should, however, be noted that differences were not
observed post-intervention between conditions which should be taken into consideration.
Although improvements were observed particularly at LT1 with healthy, recreationally
active volunteers, we did not speciﬁcally distinguish whether such effects were pertinent
to gender, training status, or the type/intensity of habitual exercise. Further research may
therefore be relevant to determine the potential applications of OliP in various cohorts.
Additionally, the protocol used in the current study was designed to standardize the
demanding aerobic run prior to the following day exercise performance session for all
participants [45]. It is important to recognize the translation of controlled laboratory
ﬁndings to real-world exercise applications [91], and future research should investigate the
adjunct use of OliP in applied and ﬁeld-based settings (e.g., single exercise sessions, events
that require repeated bouts, or multi-day events). It should also be noted that existing
literature has outlined the potential variability in polyphenol products [92]. Whilst 16-days
of OliP consumption (Batch 14) positively inﬂuenced aerobic exercise parameters and acute
recovery, results may differ between batches and additional investigation is needed to
corroborate current ﬁndings. Indeed, as previously noted, the intestinal microbiota plays
an important role inﬂuencing gut-derived phenolic metabolites, which are additionally
dependent on the phenolic composition of dietary products.
As this was the ﬁrst study to assess the use of OliP in an exercise domain, a parallel co-
hort design was employed to ascertain the inﬂuence of a single course of the phytocomplex
(16 consecutive days) whilst minimizing potential for longer term training effects. Further
research should investigate whether time course (>16-days), dose-response (>56 mL· d−1)
and/or dose-frequency (>2 serves·d−1) can inﬂuence sustained exercise training adap-
tations or accumulated recovery, i.e., during marathon training. Additional exploration
into alternate recovery periods (i.e., respiratory measures up to 1 h post exercise, and
inﬂammatory or muscle soreness measures 1, 12, 24, and 48 h+ following exhaustive ex-
ercise) is also warranted. Finally, based upon current findings, including effects of OliP on
exercise-induced oxidative stress presented elsewhere [45], it would be beneficial to assess
the potential impact of this olive-derived phytocomplex on inflammatory markers associated
with EIMD (particularly within other populations, e.g., trained athletes), or within clinical
applications where functional movement may be impacted (e.g., arthritis, fibromyalgia).
5. Conclusions
This is the ﬁrst study to investigate the use of OliP in an exercise domain. Findings
demonstrated that 16-days supplementation of OliP positively inﬂuenced parameters of
aerobic exercise, most notably at submaximal levels. Reduced oxygen cost and improved
running economy at exercise intensities corresponding with LT1, as well as improvements
in acute recovery may have implications for recreationally active individuals undertaking
demanding or repeated aerobic exercise training. Further research is warranted to cor-
roborate these ﬁndings and explore potential applications (time-course, dose-response) to
prolonged training periods and/or repetitive bouts of exercise.
Nutrients 2023, 15, 421
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Supplementary Materials: The following supporting information can be downloaded at: https:
//www.mdpi.com/article/10.3390/nu15020421/s1, Table S1: List of food sources requested to be
avoided by participants for the 3-days prior to main laboratory testing sessions; Table S2: Independent
product analysis.
Author Contributions: Conceptualization, J.D.R.; methodology, J.D.R., J.B.L., J.M.P., A.G.B.W. and
H.C.; formal analysis, J.D.R., J.B.L., J.M.P. and R.Z.; investigation, J.D.R., J.B.L., J.M.P. and H.C.;
resources, J.D.R., J.B.L. and J.M.P.; data curation, J.D.R., J.B.L. and J.M.P.; writing—original draft
preparation, J.D.R., J.B.L. and J.M.P.; writing—review and editing, J.D.R., A.G.B.W., J.M.P., J.B.L.,
Á.L.-S., J.D.C., R.Z. and H.C.; supervision, J.D.R.; project administration, J.D.R. and H.C.; funding
acquisition, J.D.R. All authors have read and agreed to the published version of the manuscript.
Funding: This research was funded by Fattoria La Vialla, Castiglion Fibocchi, Arezzo, Italy for
product and related consumables, and research/analytical costs (Number: R9039). This study was
undertaken independently of the funding company.
Institutional Review Board Statement: The study was conducted in accordance with the Declaration
of Helsinki, and approved by Faculty of Science and Engineering Research Ethics Panel, Anglia
Ruskin University (approval number: FSE/FREP/20/946; date: 13 October 2020).
Informed Consent Statement: Informed consent was obtained from all subjects involved in the study.
Data Availability Statement: The data presented in this study is available upon request from the
corresponding authors. The data is not publicly available due to ethical considerations, in accordance
with participant consent on the use of conﬁdential data.
Acknowledgments: The authors would like to acknowledge the team at Fattoria la Vialla, Castiglion
Fibocchi, Arezzo, Italy, in particular Rosa Briamonte, for their open communication and support in
this study.
Conﬂicts of Interest: The authors declare no conﬂict of interest. The funders had no role in the design
of the study; in the collection, analyses or interpretation of data; in the writing of the manuscript or
in the decision to publish results.
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The Effect of a Hydroxytyrosol-Rich, Olive-Derived Phytocomplex on Aerobic Exercise and Acute Recovery.
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