It’s the toughest and perhaps most discerning test of all. The two-day maximal exercise test requires that one exercise to exhaustion (or nearly so) two days in a row. In truth, the test is over quickly: it starts out with mild pedaling on a bicycle which slowly gets harder as the resistance is increased and is over in just 8-12 minutes.

It is, however, a maximal exercise test – you exercise to your limit – and that’s why it’s so valuable. It determines how much energy a person – not a cell or a tissue – but an entire person, can pump out.

The remarkable thing is that virtually everyone, whether they’re healthy or sick with any manner of serious diseases, are able to get on a bike, pedal to exhaustion and then pump out the same amount of energy the next day. Whether we’re sick or healthy, somehow our bodies almost always retain the ability to produce energy when needed.

But not apparently in one disease. Chronic fatigue syndrome (ME/CFS) appears to be the odd man out. Put some people with ME/CFS on a bike, and their ability to generate energy (e.g. exercise) the next day plummets. That’s an important finding in a disease which introduced the term post-exertional malaise (PEM) to the medical lexicon.

If that finding holds up – and it’s held up in a number of small studies – it would suggest that exercise does things to people with ME/CFS that it doesn’t appear to do to people with other serious diseases.

When we exercise, our bodies use two different systems – anaerobic and aerobic – to produce energy.The aerobic energy production system dominates during exercise to provide a clean and abundant source of energy. When we reach the limits of our aerobic energy production capacity, the anaerobic energy production begins to dominate – but at a cost. Not only does it produce much less energy, but it also produces toxic by-products which, as they build up, produce pain and fatigue.

The VO2 max CPET exercise test has played an important role in ME/CFS because it measures the transition from aerobic to anaerobic energy. Past two-day exercise studies have suggested that many people with ME/CFS exhaust their aerobic energy production systems more quickly than usual. That leaves them dependent on less efficient anaerobic energy production – and suffering from symptoms of pain and fatigue that quickly kick in when that system predominates.

This Norwegian two-day exercise study potentially adds something new to the accumulating evidence that something vital is broken in the energy production systems in ME/CFS: for the first time, lactate accumulations over two exercise tests were assessed.

Lactate – a byproduct of anaerobic energy production – is produced throughout an exercise period, but as the anaerobic energy production system becomes more dominant, lactate accumulations build up. Increased lactate accumulations, then, in ME/CFS, would add another sign that people with ME/CFS are more dependent upon anaerobic energy production than healthy controls.

The Study

Abnormal blood lactate accumulation during repeated exercise testing in myalgic encephalomyelitis/chronic fatigue syndrome. Katarina Lien1,2 , Bjørn Johansen3, Marit B. Veierød4, Annicke S. Haslestad1, Siv K. Bøhn1, Morten N. Melsom5, Kristin R. Kardel1 & Per O. Iversen1,6. 1 Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Physiol Rep, 7 (11), 2019, e14138, https://doi.org/10.14814/phy2.14138

As we saw with Rituximab, small countries like Norway can make big waves in ME/CFS if they apply themselves. Now comes another ME/CFS study from Norway, this time led by Katarina Lien.

Lien put 18 women with ME/CFS (who fulfilled the Canadian Consensus Criteria) and 15 healthy females (18–50 years) on the bike for two maximal exercise periods one day apart.

Some Terms

Tip – Because our cells use oxygen to produce aerobic energy, oxygen consumption is used to assess the amount of energy produced. Therefore, translate “oxygen consumption” into “energy production” when you hear it.

Peak VO2 – Peak VO2 describes the highest rate of oxygen consumption (energy production) that occurs at some point during the exercise test. Because peak VO2 is a one-time measure which can occur at any point during the test, it tells us nothing about the ability to consistently do work, and is not particularly important. Much more important for our concerns is the level of oxygen consumption at GET (Gas Exchange Threshold) or “anaerobic threshold”. (GET in this context does not refer to graded exercise therapy.)

Gas Exchange Threshold (GET) – GET is the point where carbon dioxide levels in the breath rapidly begin to build – indicating that anaerobic energy production has begun to dominate. (It appears to be the same as the anaerobic threshold).

Lactate Levels and Lactate Turnpoint – Once the limits of aerobic energy production are reached and anaerobic energy production begins to dominate, increased levels of lactate are produced. Lactate levels can rise very quickly – just two or three minutes of anaerobic energy production are needed to produce high lactate levels. The “lactate turnpoint” is the point at which lactate levels begin to rise very quickly.

Lactate does not cause pain or fatigue. Contrary to what was previously thought, lactate actually helps to retard these symptoms, but high lactate levels are associated with the acidosis responsible for the pain and fatigue when we rely on anaerobic energy production. For our purposes, then, high lactate levels mean increased levels of pain and fatigue.

Absolute Power Output – Absolute power output assesses the amount of power (in watts) produced, adjusted for a person’s size.

Rigor

The authors went to some lengths to ensure their results couldn’t be explained away by deconditioning or some other factor. All the ME/CFS patients had “mild to moderate” ME/CFS (none were bedbound), all had normal hemoglobin concentrations, and all had normal breathing before the exercise test and normal to high “breathing reserve” during the exercise test. Age, gender and height were similar as well. The patients were a bit heavier, but when weight was controlled for, the results did not change.

Healthy controls were deemed ineligible to participate if they were too active (exercised more than once per week). Both the patients and controls had similar mean respiratory exchange ratios and maximum heart rates; i.e. both exerted themselves fully during the test.

Results

Oxygen consumption (VO2) ( i.e. energy production) at the entry into anaerobic energy production (GET) was significantly reduced in the ME/CFS patients compared to healthy controls in both exercise tests. This indicated that ME/CFS patients began having trouble producing energy at a significantly lower exercise level than the healthy controls.

The significantly reduced power output at GET in the ME/CFS patients on both exercise studies indicated the same. It indicated that it took significantly less work for the ME/CFS patients to exhaust the capacity of their aerobic energy production system and begin relying on anaerobic energy production.

Changes from the First Exercise to the Second Exercise Test – the PEM Test

VO2 – Oxygen consumption (energy production)

Despite exercising to exhaustion on the first day, the healthy controls were able to match their energy outputs during the exercise test on the second day. In fact, in some ways they even got stronger.

The ME/CFS patients were not so lucky. Several results suggested that the first exercise session blunted their ability to generate energy. The maximum amount of energy they produced (VO2 peak), and the amount of energy the patients were able to produce before they entered anaerobic energy production (GET), was significantly reduced during the second exercise test.

The second test was particularly important, as a drop in oxygen consumption at GET indicates a quicker entry into anaerobic energy production, fatigue and pain.

Lactate

The lactate results uncovered more significant abnormalities and a sharp divide began to appear. While the healthy controls got stronger on the second exercise test, the ME/CFS patients got weaker.

The lactate levels were similar in both groups at rest, but as soon as the exercise started, things started to go haywire for the ME/CFS patients.

People with ME/CFS had an earlier lactate turnpoint – another sign of earlier entry into anaerobic energy production – during the first and second exercise tests. The fact that ME/CFS patients consistently demonstrated significantly increased lactate levels at any work level (power output) suggested they’d exhibited an increased reliance on anaerobic energy production throughout the test.

The significantly increasing lactate levels the ME/CFS patients produced per power output on the second exercise test indicated they were relying more and more on anaerobic energy production.

Healthy Controls Get Stronger / People with ME/CFS Get Weaker

While ME/CFS patients’ lactate levels at GET significantly increased from the first to the second exercise tests, in the healthy controls lactate levels actually decreased.

Plus, the healthy controls were able to tolerate the lactate that was present better (their lactate levels at the lactate turnpoint increased). They were able to work harder at the second test before their lactate levels began rising rapidly. These findings indicated that the healthy controls’ bodies were rapidly adjusting to and benefitting from the exercise.

The ME/CFS patients, however, showed just the opposite. Their lactate levels began to rise rapidly at significantly lower work levels, their lactate levels at GET increased significantly relative to the healthy controls, and neither their lactate levels at GET, nor their lactate turnpoint improved during the second exercise test.

When assessed for absolute power output, the pattern was the same: more lactate accumulated in the blood of the ME/CFS patients and they entered into anaerobic energy production earlier during the second exercise test.

As the healthy controls produced less lactate and were able to tolerate it better, the ME/CFS patients produced more lactate at lower levels of work. This, in effect, told the tale of how exercise makes an ME/CFS patient weaker while making a healthy person stronger.

Peak VO2

Peak VO2 is the least significant test made as it is a one-time measure of energy consumption.

VO2 at peak exercise (VO2peak) was, however, significantly lower in patients than in controls during the first exercise test and decreased further on the second exercise test.

The authors cited several studies which could provide clues to the exertion problems in ME/CFS including reduced energy production of immune cells, reduced AMPK phosphorylation and glucose uptake in muscle cells, disturbed PDK regulation, elevated LPS levels and exercise induced leaky gut.

Conclusion

The authors’ conclusion was as devastating as it was simple:

“exercise deteriorates physical performance and increases lactate during exercise in patients with ME/CFS while it lowers in healthy subjects”. Lien et al.

Numerous data points indicated that instead of making people with ME/CFS stronger, a maximal exercise test one day impaired their ability to generate energy the next day. While lactate accumulations were not significantly increased in the ME/CFS patients during the second exercise test they were significantly increased throughout the tests when power output was taken into account. The earlier lactate turnpoint also suggested ME/CFS patients enter into anaerobic functioning earlier during exercise as did decreased oxygen consumption at anaerobic threshold (or GET).

The lactate accumulations add an important data point. Past ME/CFS lactate studies have had mixed results, but none had applied the crucial element – the second day exercise test regimen that Workwell introduced into the field so many years ago. Now we have another data point which indicates the havoc that exercise – in this case a short but intense bout of exercise – wreaks on ME/CFS patients’ ability to produce energy.

ME/CFS, in effect, got lucky when a small team of exercise physiologists at the University of the Pacific in Stockton, California introduced a vital element to this field: the two-day exercise test. Adding that second day uncovered a possibly unique feature of ME/CFS (inability to reproduce energy the second day), biologically validated the existence of post-exertional malaise (PEM), demolished the idea that deconditioning is responsible for the exertion intolerance in ME/CFS, and provided an objective test that has proved crucial in disability cases.

Exercise is a hot topic right now. Blogs on several more exercise studies are coming up, plus Workwell begins its Medbridge educational program for rehabilitation professionals treating people with ME/CFS.