Highlights

  • An intensive round of exercise preserves cardiac function against treatment with the chemotherapeutic agent doxorubicin.
  • Nicotinamide mononucleotide (NMN) and nicotinamide adenine dinucleotide (NAD+) levels fall in the heart following doxorubicin treatment, but high-intensity exercise prior to treatment preserves their levels.
  • Sufficient NAD+ is essential for generating cell energy, and intensive exercise preserves cell energy production against doxorubicin treatment.


Chemotherapy damages the heart in approximately 10% of patients. Heart injury can lead to heart failure, resulting in death for about 50% of those with heart damage. Currently, a lack of effective methods exists to prevent chemotherapy-induced heart damage. Interestingly, a brief exercise session prior to administering chemotherapy may protect against chemotherapy-induced heart injury, but this intervention remains underexplored.

In a not yet peer-reviewed publication, Xing and colleagues from Qingdao University in China show that a session of intermittent intensive exercise preserves heart function against doxorubicin treatment. Heart protection against doxorubicin likely stemmed from the intensive exercise session increasing NMN and NAD+ levels. Further results showed that the pre-doxorubicin exercise session maintained cell energy molecule (adenosine triphosphate [ATP]) production. These data support that an intensive exercise session before doxorubicin preserves cardiac function likely by preserving NMN and NAD+ levels, which increases cellular ATP levels.

Exercise Preserves Heart Function Against Chemotherapy by Increasing NMN, NAD+, and Cell Energy

To find whether an intensive exercise session prevents cardiac damage, Xing and colleagues subjected rats to four, 10-minute repetitions of running at a speed of 25 meters/minute 24 hours prior to doxorubicin treatment. They then measured what effect the exercise had on the amount of blood ejected with each pump, the ejection fraction, following doxorubicin treatment. The researchers found that doxorubicin damaged the heart as shown by a markedly lower ejection fraction but that high-intensity exercise before doxorubicin treatment restored the ejection fraction. These findings support that intensive exercise before chemotherapy treatment preserves cardiac function, indicating protection against chemotherapy-induced damage.

(Yuan et al., 2023 | SSRN) Doxorubicin chemotherapy alters heart function as shown by falling ejection fractions, but intensive exercise before treatment preserves function. The ejection fraction significantly fell with doxorubicin (DOX) compared to healthy rats (C). Exercise preconditioning before chemotherapy (EP-DOX) maintained heart function shown by a preserved ejection fraction percentage (EF[%]).

Since previous studies have shown that NMN protects against doxorubicin-induced heart damage, Xing and colleagues sought to find whether NAD+ and its NMN precursor play a role in exercise’s benefits against chemotherapeutic treatment. The researchers measured heart NMN and NAD+ levels and found that doxorubicin statistically reduced heart tissue NMN and NAD+ levels. The intensive, pre-doxorubicin treatment exercise routine restored NMN and NAD+ levels. These results suggest that tissue NMN and NAD+ levels play a role in exercise’s beneficial effects against chemotherapy.

(Yuan et al., 2023 | SSRN) Intensive exercise increased NMN and NAD+ heart tissue levels against doxorubicin chemotherapy. NMN and NAD+ levels significantly fell with doxorubicin treatment (DOX) compared to healthy (C), but intensive exercise (EP+DOX) prior to treatment restored their levels in heart tissue.

Since NAD+ is involved in a number of cell energy generation reactions and is necessary for sufficient cell energy production, the researchers measured ATP production. They found that doxorubicin treatment substantially hampered ATP production but that exercising before doxorubicin treatment restored ATP production. These results provide evidence that exercise increases NAD+ along with its NMN precursor to drive ATP production and preserve heart health.

(Yuan et al., 2023 | SSRN) Intensive exercise preserves ATP production against doxorubicin chemotherapy treatment. The oxygen consumption rate (OCR) is an indicator of ATP production, and compared to healthy rats (C), doxorubicin (DOX) reduced ATP production. Intensive exercise preconditioning (EP) increased ATP, even with doxorubicin (EP-DOX).

Uncovering the Benefits of NMN Combined with Exercise

The study’s findings support that exercising can boost NMN and NAD+ levels to counter the detrimental effects of chemotherapy treatment. The study also shows evidence that exercise alone can boost cellular NMN, NAD+, and ATP production. Future studies should examine whether NMN supplementation in combination with exercise can further increase NAD+ and ATP production and whether doing so would benefit heart function.