REF-1534 · Cardinale et al., 2021 · Journal of Applied Physiology · Paper · PubMed

Does a hard block damage the mitochondria?

In 27 athletes after 4 weeks of three added quality sessions a week, muscle respiration was about 20% lower while density markers rose; the authors report performance improved days later.

Main caveat: Read from the abstract only. The full text is not openly available, so the training prescription, the statistics, the biopsy timing, the sex split, the…
limited, mixed evidenceMeasured on elite athletes

Twenty-seven athletes described as elite endurance athletes added, to their usual training volume, interval work at high intensity, each time followed by a continuous moderate session, on three days a week for four weeks.

Muscle biopsies before and after the block were used to measure mitochondrial oxidative capacity, how much mitochondrial protein was present, autophagy markers, and the muscle's antioxidant capacity.

After the block, mitochondrial respiration in permeabilised muscle fibres was about 20% lower, although some markers of mitochondrial density were 5-50% higher, which the authors read as a loss of mitochondrial quality. Several autophagy markers increased, which they take as faster turnover of mitochondrial and cytosolic proteins.

The antioxidant-related proteins UCP3, ANT1 and SOD2 increased, aconitase was inactivated, and the amount of mitochondrial LON protease, which breaks down oxidised aconitase, doubled. The authors' own summary states that performance improved a few days after the intense training period, despite the respiratory impairment.

Our reading: a rare set of biopsies in top athletes through an overload block, and a useful warning that a muscle measurement taken right after hard work can look worse while the athlete gets faster.

With no control group, no numbers for performance or oxygen uptake in the abstract, and one post-block measurement reported, it describes what happened after the block rather than proving what the block did.

Protocol (from the abstract; the full text is not openly available)

Who: n = 27, called elite endurance athletes and highly trained. No sex split, age, body mass, VO2max, training history or discipline in the abstract.
Intervention: on 3 days a week for 4 weeks, intervals at high intensity and then a continuous session at moderate intensity, in addition to the athletes' usual volume of training. The interval prescription, the duration and intensity of the continuous part, and the total weekly load are not in the abstract.
Design: before-and-after, with no control or comparison group described. No randomisation, because there is nothing to randomise; no blinding.
Measures named: mitochondrial oxidative capacity (respiration in permeabilised muscle fibres), abundance of mitochondrial proteins, markers of autophagy, antioxidant capacity, maximal oxygen uptake and performance. Biopsies before and after the period. The timing of the post-block biopsy relative to the last session is described in the abstract only as the initial recovery.
Not readable here: sample-size calculation, statistics, effect sizes, dropout, nutrition control, and the performance and oxygen-uptake numbers.
Funding and interests: the publication record lists support from Team Denmark, the Swedish Research Council for Sport Science and the Danish Ministry of Culture. A conflict-of-interest statement could not be read.

Key Results

MeasureWhat was reported
Mitochondrial respiration, permeabilised fibresabout 20% lower after the block
Markers of mitochondrial densityincreased by 5-50%
Autophagy markersseveral increased
UCP3, ANT1, SOD2increased after training
Aconitaseinactivated
Mitochondrial LON proteasedoubled
Mitochondrial biogenesisdescribed as slightly activated
Performanceimproved a few days after the block (no numbers in the abstract)
Maximal oxygen uptakenamed as an aim; no result in the abstract
Respiration down while density markers were up. The authors read the two together as lower mitochondrial quality: more mitochondrial material, less oxygen flux per unit of it. The abstract gives one range (5-50%) across several markers and no values.
Did the drop recover? The title says the impairment is temporary and the conclusion places it in the initial recovery from the block, but the abstract reports measurements before and after only. No second post-block biopsy is described there, so a return to baseline is not shown in what could be read.
Performance and oxygen uptake. The improvement a few days later is stated in the authors' own highlight paragraph without a number, a test or a p value; the oxygen-uptake result is absent from the abstract. Both were named as aims, so the paper has them and this entry does not.
Before-after, not an effect (inference). Everything here is the change across four weeks in athletes who were also doing their normal training, in whatever season and conditions; with no control group, the block, the season and the timing of the biopsy cannot be separated.
Reporting. The body of the abstract names ANT1 among the proteins that increased and the highlight paragraph names ANT2. Which is correct cannot be settled from the abstract.

Mechanisms

Measured: lower respiration per unit of muscle fibre with higher density markers; higher autophagy markers; higher UCP3, ANT1 and SOD2; inactivated aconitase with twice as much of the protease that clears it.
Authors' interpretation: mitochondrial respiratory function is impaired during the early recovery from a block of intensified endurance training, while the quality-control system — biogenesis together with the removal of damaged mitochondria — is mildly switched on. The aconitase and LON protease pattern fits oxidative stress inside the mitochondria.
Inference: this is the mirror image of REF-1532's pulse. A single session switches the growth programme on; four weeks of extra hard sessions left the muscle mid-rebuild, with the measured function lower while the material was being replaced. The two readings are consistent but neither measures the adaptation itself (PHYS-18, REF-465).
Inference: if performance improved while respiration was down, as the authors state, then a muscle marker taken straight after a hard block is not a verdict on the athlete. That is the same logic the base applies to overreaching markers (PHYS-27, REF-207): performance decides, not one measurement.

Practical Application

Does a hard block damage the mitochondria? In 27 athletes after 4 weeks of three added quality sessions a week, muscle respiration was about 20% lower while density markers rose; the authors report performance improved days later.
Good for: patience right after an overload block. The muscle's measured function can be at its worst while the athlete is about to be at their best, so a muscle measurement taken in the first days after the block can look worse than the athlete is — in this study performance improved a few days later.
Good for: describing what four weeks of extra quality on top of a full volume left in the muscle of athletes at this level: respiration down, density markers up. With no control group, and performance reported as improved, it is not an argument against the dose.
Not good for: a dose. The interval prescription, the continuous part and the weekly load are not readable here, so this supports no session design and no block length.
Not good for: the Norwegian double-threshold question. The added sessions here were intervals followed by continuous work, not two sub-threshold sessions in a day; SYNTH-03 carries what the base can say about that, and this paper adds nothing to it.
Not good for: a claim that respiration recovers, or when. One post-block measurement is reported in the abstract; the word "temporarily" is the authors' reading of it.
Practice, not from this paper: judge an overload block by what the athlete can do a week or two later, and keep the hard block short enough that the taper can land (PHYS-27, REF-1056).

Limitations

Read from the abstract only. The full text is not openly available, so the training prescription, the statistics, the biopsy timing, the sex split, the performance and oxygen-uptake data and the conflict-of-interest statement are unknown here.
No control group. Everything is a change over four weeks in athletes who continued their normal training; the block cannot be separated from the season, the testing order or the timing of the second biopsy.
Markers, not the athlete's outcome. Respiration in permeabilised fibres, protein abundances and enzyme activity are what was measured. The performance claim carries no number, test or statistic in the abstract.
One post-block measurement reported. The title's word for the impairment is temporary, but a return towards baseline is not shown in what could be read.
"Elite" is the authors' label. With no VO2max, discipline or results, the tier cannot be checked, and n = 27 at that level usually means several sports pooled (our inference).
The density range is wide. "5-50%" covers several different markers; without values and spreads, how much mitochondrial material actually changed cannot be judged.
A dose nobody prescribes. Three added quality sessions a week on top of a full volume for four weeks is a deliberate overload, so the findings describe that extreme, not a normal training week.
How this entry was checked and changed
Why this level

an uncontrolled pre-post earns B by design, lowered one step because the outcomes are muscle markers rather than the athlete's performance (which is mentioned without numbers), and because it was read from the abstract, so the training dose, the test battery, the group's sex split and the statistics could not be checked