Table 1.
Summary of the characteristics of included studies
| Disease | Author(s) and year | Subjects | Exercise/nutritional intervention and duration | Outcomes |
|---|---|---|---|---|
| GSD V | Haller et al. 2006 | Eight patients (four males and four females) Mean age: 43.25 years (range: 33–61) | Aerobic training: cycling, 4 sessions per week at 60%–70% of maximal HR for a duration of 30 min per session during the first 7 weeks and of 40 min per session during the last 7 weeks, over a period of 14 weeks |
↑ Peak cardiac output ↑ V̇O2max = CK |
| Maté-Muñoz et al. 2007 | Nine patients (four males, five females) Mean age: 36 ± 5 years (range: 17–69) | Aerobic training: walking or cycling, 5 sessions per week at 60% of peak HR for an incremental duration from 10 to 60 min per session, combined with a nutritional approach over a period of 8 months |
↑ V̇O2peak ↑ Ventilatory threshold ↓ CK (Δ pre- and post-exercise, before and after the intervention): Pre-training: rest 2235.8 ± 2082.1 U/L, post-exercise 2283.8 ± 1875.6 Post-training: rest 595.1 ± 1074.3 U/L, post-exercise 711.4 ± 1104.0 U/L |
|
| Lucia et al. 2007 | A 29-year-old-female patient | Aerobic training: walking, 5 sessions per week at ~ 60% of maximal HR for an incremental duration from 10 to 60 min per session, combined with a nutritional approach over a period of 12 weeks |
↑ V̇O2peak ↓ CK level (Δ pre- and post-exercise, before and after the intervention): Pre-training: rest 5278 U/L, post-exercise 5443 U/L Post-training: rest 448 U/L, post-exercise 460 U/L |
|
| Pérez et al. 2007 | A 38-year-old-male patient | Aerobic training: running, 3–4 sessions per week at ≤ 80%-85% of maximal HR for an incremental duration from 10 to 60 min per session, combined with a nutritional approach over a period of 7 months |
↑ V̇O2peak ↓ CK (Δ pre- and post-exercise, before and after the intervention): Pre-training: rest 5682 U/L, post-exercise 5700 U/L Post-training: rest 2641 U/L, Post-exercise 2805 U/L |
|
| Pérez et al. 2008 | An 8-year-old-male patient | Aerobic training: 2–3 non-competitive swimming classes per week and 1–2 physical education classes per week, combined with a nutritional approach over a period of one year | ↓ CK (Δ basal level pre- and post-intervention): From 1570 U/L to 251 U/L | |
| Pietrusz et al. 2018 | Two patients, a 37-year-old male and a 46-year-old male | Anaerobic training: Patient 1, four sessions per week over a period of 4 years, composed by exercises mainly performed using free weights compound movements, with sets of 1–5 repetitions and a variable resting time of 2–5 min between sets and occasional sets of 4 repetitions with a rest of 30 s. Patient 2, protocol based on the use of resistance machines over a period of 3 months, with sets of 5 to 15 repetitions per exercise, stopping as soon as muscle discomfort occurred, and 1 min rest between sets |
↑ Muscle strength for one patient ↑ Training workload for one patient = CK for one patient ↓ CK for one patient: From 2011 to 2014 CK mean: 3006 U/L From 2015 to 2017 CK mean: 1029 U/L 2017 July CK assessment: 941 U/L |
|
| García-Benítez et al. 2013 | A 15-year-old-male patient | Anaerobic training: 2 sessions of 60 min of 8 resistance exercises per week, with 2–3 sets of 10–15 repetitions at 60%–75% of 1RM, with 1–3 min rest between sets (after 5 min of cycle/rowing ergometer and 5 min of mobilization warm-up), combined with a nutritional approach over a period of 6 weeks |
↑ Muscle power ↑ Muscle force ↓ CK: Post 1RM CK pre-training: 3636 U/L Post 1RM CK post-training: 1575 U/L |
|
| Santalla et al. 2014 | Seven patients (two males, five females) Mean age: 38.4 years (range 23–58) | Anaerobic training: 2 sessions of 4 resistance exercises performed as a circuit per week, with 4–6/6–8 sets of 5–6 repetitions at 6–7 of RPE, with 2–3 min rest between sets (after 12 min of arm crank ergometer plus 12 min of cycle ergometer warm-up), combined with a nutritional approach over a period of 16 weeks |
↑ Lean mass ↑ Strength = CK levels |
|
| Santalla et al. 2022 | Ten patients (six males, four females) Mean age: 38 ± 18 years | Aerobic training: cycling, 5 sessions per week at 5–7 RPE and 0–1 RPP for an incremental duration from 15 to 60 min per session; anaerobic training: 2–3 sessions per week, with 3 circuit laps per session, each with 3 sets of 4 exercises with 6 repetitions at 6–7 OMNI-RPE and 0–1 RPP, with 2–3 min rest between sets, combined with a nutritional approach over a period of 2 years |
↑ V̇O2peak ↑ Ventilatory threshold ↑ Training workload = CK level |
|
| GSD X | Kissel et al. 1985 | A 24-year-old-male patient | Exercise sessions: running on treadmill during which speed and inclination were increased every minute, starting from 1.5 mph up to 5.5 mph and from a 4% inclination to 20% | = CK |
| GSD XIII | Buch et al. 2021 | Three patients, a 21-year-old-male, a 41-year-old-male, and a 50-year-old-male | Exercise sessions: a hand grip strength test, a maximal incremental cycle ergometer test, and up to 1-h submaximal cycling exercise test at 65%–75% of V̇O2max |
Glucose infusion = no effect ↑ CK from rest to peak: Patient 1, from 126 U/L (rest) to 374 U/L (peak) Patient 2, from 931 U/L (rest) to 2530 U/L (peak) Patient 3, from 94 U/L (rest) to 121 U/L (peak) |
| GSD XIV | Voermans et al. 2017 | A 53-year-old-male patient | Exercise sessions: two incremental cycling tests peaked at 65 Watts and two constant submaximal 30 Watts-workload cycle ergometry, combined with a nutritional approach |
↓ CK (Δ peak pre- and post-exercise, before and after the intervention): Pre-intervention: rest from 2500 U/L, post-exercise 13,600 U/L Post-intervention: rest from 875 U/L, post-exercise 3130 U/L |
| PGK-1 | Hogrel et al. 2019 | A 69-year-old-male patient | Exercise session: maximal hand grip strength test sustained for 30 s | ↑ CK: From 544 U/L to 1920 U/L |
| CPT II | Parimbelli et al. 2021 | A 14-year-old-female patient | Anaerobic training: 3 sessions of 1 h per week composed by an interval training performed as 1 min run at above 70% of maximal HR and 5 min walk, for an incremental duration from 15 to 30 min, followed by 6 resistance exercises with 3 sets of 8 repetitions at 6–7 of the OMNI scale, with 2 min rest between sets, combined with a nutritional approach over a period of 6 months |
↑ V̇O2peak ↑ Peak power output ↑ Ventilatory threshold ↑ Oxygen pulse = CK |
| Crisafulli et al. 2024a | An 18-year-old-male patient | Anaerobic training: the patient kept his competitive sport activity but no specifics are available, combined with a nutritional approach over a period of 5 months | = CK | |
| LCHAD | Karall et al. 2014 | A 13-year-old-male patient | Exercise sessions: incremental cycle test, with increasing of 25 Watts every 2 min until exhaustion, and 3 endurance tests of 30 min each at 80, 90, and 100 Watts, respectively, combined with a nutritional approach | = CK |
| van Eerd et al. 2017 | A 34-year-old-female patient | Exercise sessions: 4 min of unloaded cycling warm-up followed by increasing workload of 1 Watt every 5 s at a pedal frequency of 60–80 RPM until exhaustion, combined with a nutritional approach over a period of one month |
↑ Peak power output ↑ HR ↑ V̇O2max ↓ CK (rest and max): Session 1: rest 183 IU/L, max 197 IU/L Session 2: rest 135 IU/L, max 139 IU/L Session 3: rest 110 IU/L, max 115 IU/L |
|
| VLCADD | Herrera-Olivares et al. 2019 | A 23-year-old-female patient | Anaerobic training: one-month of 2 HIIT sessions per week followed by 5 months of 2 HIIT sessions plus 2 resistance exercises sessions per week (HIIT sessions consisted of 6 sets of 70–80 s on a cycle ergometer at a pedal frequency of minimum 100 RPM with 1 min rest between sets. The 6 resistance exercises were performed as 2 circuit laps of 4–7 repetitions at 5–7 of OMNI scale with 2 min rest between sets and 4 min rest between laps), combined with a nutritional approach over a period of 6 months |
↑ V̇O2peak ↑ Maximal power output ↑ Maximal HR = CK |
| Diekman et al., 2016 | Five patients (four males and a female) Mean age: 28 years (range: 13–37) | Exercise sessions: maximal incremental cycle ergometer test with increasing of 35 Watts every 3 min until exhaustion, and endurance cycle ergometer test at FATMAX for a duration of 45 min |
= CK in 3 patients ↑ CK in 2 patients of which one RML: Patient 1: from 156 U/L to 576 U/L Patient 2 (RML): from 36 U/L and to 400 U/L |
|
| Bleeker et al., 2020 | Five patients (four males and a female) Median age: 22 years (range: 17–45) | Exercise sessions: maximal incremental cycle ergometer test and endurance cycle ergometer test at FATMAX at a pedal frequency of 60–80 RPM for a duration of 45 min, combined with a nutritional approach |
↑ HR = CK |
|
| LPIN-1 | Legendre et al. 2018 | Eight patients (five males and three females) Mean age: 11.8 ± 3.6 years (range: 6.1–15.5) | Exercise session: maximal incremental cycle ergometer test at increasing load from 5 to 15 Watts until exhaustion) | = CK |
| Raaschou-Pedersen et al. 2019 | A 48-year-old-male patient | Exercise sessions: a maximal exercise cycle ergometer test to exhaustion and 4 one-hour submaximal cycle ergometer exercise tests at ~ 60% of V̇O2max, combined with a nutritional approach |
Less post-exercise CK increments with IV glucose, oral placebo, and oral glucose compared to a preliminary session Post-preliminary session CK: 4400 U/L Post-IV glucose session CK: 1330 U/L Post-placebo session CK: 676 U/L Post-oral glucose session CK: 752 U/L |
↑, increased; ↓, decreased; = equality
BPM, beats per minute; CK, creatine kinase; CPT II, Carnitine Palmitoyl-Transferase II; FATMAX, maximal fat oxidation; HR, heart rate; HIIT, high-intensity interval training; IU/L, international unit per liter; IV, intravenous; GSD, glycogen storage disease; 1RM, one-repetition maximum; LCHAD, long-chain 3-hydroxyacyl-CoA dehydrogenase; LPIN1, lipin-1; mph, miles per hour; PGK-1, phosphoglycerate kinase-1; RPE, rating of perceived exertion; RPP, rating of perceived pain; U/L, unit per liter; VLCADD, very-long-chain acyl-CoA dehydrogenase deficiency; V̇O2max, maximal oxygen uptake; V̇O2peak, peak oxygen uptake