Cancer treatment is hard on the body in ways most patients don’t fully expect going in. The nausea, fatigue, and hair loss get talked about. What doesn’t get talked about nearly enough is what chemotherapy does to the body’s immune system at a molecular level, and specifically, what it does to a molecule called nitric oxide. If you or someone you love is going through chemo, this article breaks down what nitric oxide actually is, how chemotherapy interacts with it, and what current research is revealing about its role in immune health during treatment.
Cancer is not a rare disease. According to the National Cancer Institute (NCI), an estimated 2,041,910 new cancer cases will be diagnosed in the United States in 2025 alone, with 618,120 projected deaths from the disease. [Source: Cancer.gov] Globally, the American Cancer Society’s Global Cancer Statistics 2024 report found that 20 million new cancer cases were diagnosed in 2022, with 9.7 million deaths. By 2050, that number is projected to climb to 35 million new cases per year. [Source: American Cancer Society] The majority of those patients will undergo some form of chemotherapy. And almost every single one of them will deal with the immune suppression that comes with it.
Nitric oxide (NO) is a gas the body makes on its own. It’s produced primarily from an amino acid called L-arginine, through a family of enzymes called nitric oxide synthases (NOS). It’s not some fringe molecule. In 1992, Science magazine named nitric oxide its “Molecule of the Year.” In 1998, three scientists were awarded the Nobel Prize in Physiology or Medicine for discovering its role as a signaling molecule in the cardiovascular system. Inside your body, nitric oxide does three things especially well:
Vasodilation – it relaxes blood vessel walls, improving blood flow and oxygen delivery throughout the body.
Immune regulation – it activates and coordinates the immune cells that protect you from infection and disease.
Cellular signaling – it acts as a messenger between cells, regulating everything from inflammation to cell death.
That second function, immune regulation, is the one that becomes critically important when someone is going through chemotherapy. According to a review published on PubMed (NIH), nitric oxide “has been recognized as one of the most versatile players in the immune system,” regulating the functional activity, growth, and death of key immune cells including macrophages, T lymphocytes, natural killer (NK) cells, neutrophils, and antigen-presenting cells. [Source: PubMed/NIH] In plain terms: if NO is compromised, your immune system’s ability to do its job is compromised.
Here’s a fact that isn’t talked about enough: most adults are already dealing with declining nitric oxide production long before a cancer diagnosis. Research published in PMC (NIH) concludes that “enzymatic production of NO declines steadily with increasing age in healthy human subjects.” Some estimates suggest that by age 40, natural NO output may have dropped by more than 50% compared to early adulthood. [Source: PMC/NIH] A separate study published in Cardiovascular Research (Oxford Academic) confirmed that platelet NO production and responsiveness both decrease with age, findings that have broad implications for vascular health, immune function, and recovery capacity. [Source: Oxford Academic / Cardiovascular Research] What this means is that many cancer patients, particularly older adults, are entering chemotherapy with already-reduced nitric oxide levels. And then the chemo itself delivers another blow.
Chemotherapy works by targeting rapidly dividing cells. Cancer cells divide quickly, but so do many healthy cells, including those in the bone marrow that produce white blood cells, red blood cells, and platelets. According to BreastCancer.org, chemotherapy is “the cancer treatment most likely to weaken the immune system,” with the greatest impact falling on white blood cells, the front-line defenders of the immune system. [Source: BreastCancer.org] After chemotherapy ends, most patients assume their immune system bounces back quickly. The reality, according to research from the University of Leeds highlighted by Fred Hutchinson Cancer Center, is that immune suppression can persist for up to nine months after treatment concludes, far longer than most people realize. [Source: Fred Hutchinson Cancer Center]
The connection between chemotherapy and nitric oxide goes deeper than just general immune suppression. A study published on PubMed (NIH) looked specifically at non-small cell lung cancer (NSCLC) patients before and after chemotherapy. Researchers measured levels of inducible nitric oxide synthase (iNOS), the enzyme responsible for producing NO in immune cells during inflammation and immune response. The finding: iNOS levels on granulocytes and monocytes were significantly lower in the post-chemotherapy group compared to the pre-chemotherapy group. In other words, the very enzyme mechanism that enables immune cells to produce nitric oxide was measurably reduced after chemo. [Source: PubMed/NIH] That’s not a trivial finding. When iNOS activity drops, the immune system loses some of its capacity to generate the NO it needs to fight infection, regulate inflammation, and coordinate the cellular responses that keep you healthy during an already vulnerable period.
Beyond what chemotherapy does to nitric oxide levels, a separate and equally compelling area of research looks at what nitric oxide might do for cancer treatment outcomes.
A 2023 peer-reviewed study published in the International Journal of Molecular Sciences (MDPI), authored by researchers at the National Institute of Environmental Health Sciences (NIH), found that nitric oxide at high concentrations is cytotoxic to cancer cells. The study also found that NO “sensitizes various clinically active anticancer drugs” and has been shown to reverse multi-drug resistance in tumor cells that express certain resistance proteins. [Source: MDPI / International Journal of Molecular Sciences, NIH] Multi-drug resistance is one of the biggest challenges in oncology. When a cancer cell learns to pump chemotherapy drugs back out before they can cause damage, standard treatments stop working. The possibility that NO could help reverse that mechanism is one of the reasons this research area has accelerated.
Research published in the Journal of Controlled Release (2023) specifically highlighted “nitric oxide-driven nanotherapeutics” as an emerging approach in cancer treatment, leveraging NO’s biological properties to improve drug delivery and treatment efficacy. [Source: PubMed / Journal of Controlled Release] Important note: The research above involves controlled, targeted delivery of NO compounds in clinical settings. This is distinct from everyday dietary or supplemental support of the body’s natural NO production. The two are related in that they both involve nitric oxide, but they operate at very different levels. Discuss any questions about NO-based therapy with your oncology team.
While clinical NO therapy is still in development, supporting the body’s natural nitric oxide production through diet and lifestyle is well-documented and accessible to most people. This matters because, as we’ve established, NO levels are often already depleted in older adults, and chemo compounds that depletion.
The most effective dietary route to NO is through nitrate-rich foods. When you eat nitrates, bacteria in your mouth convert them to nitrites, which are then converted to nitric oxide in the bloodstream. According to Healthline, consuming a beet juice supplement increased nitric oxide levels by 21% within 45 minutes in a study of 38 adults. [Source: Healthline] According to GoodRx, leafy greens account for roughly 80% of the average daily nitrate intake, making them the most consistent dietary source of NO support available. [Source: GoodRx] The top food sources for natural NO support include:
Beets and beet juice – highest nitrate density of any common vegetable
Leafy greens – spinach, arugula, kale, Swiss chard, and cabbage
Watermelon – rich in L-citrulline, which converts to L-arginine and then to NO
Nuts and seeds – walnuts, almonds, and pecans are high in L-arginine, which is the direct precursor to NO production via the enzymatic pathway
Garlic – boosts nitric oxide synthase activity, the enzyme that produces NO from L-arginine
Citrus fruits – vitamin C enhances NO bioavailability and absorption
Even light aerobic activity stimulates eNOS (endothelial nitric oxide synthase), encouraging blood vessels to produce more NO. This doesn’t require intense exercise; regular walking is enough to have a meaningful effect. Smoking significantly depletes NO availability, which is another reason oncologists consistently advise against it during treatment.
For some people, particularly older adults whose natural NO production has already declined, dietary approaches alone may feel insufficient, or may be hard to maintain consistently during treatment when appetite and digestion are affected by chemo. This is where targeted supplementation can become part of the conversation to have with a healthcare provider. Real Science Nutrition’s Immune Boost+ is formulated specifically to support the body’s nitric oxide production and immune function. The product is designed with the understanding that adults over 40 already produce less NO naturally, and that supporting those levels can make a meaningful difference in how the immune system performs. As always, any supplement should be discussed with your oncologist before adding it during active treatment.
Nitric oxide research in oncology is active, credible, and growing, but it’s not finished. What we know clearly is that NO plays a fundamental role in immune defense; that chemotherapy measurably affects NO-related immune markers; and that declining NO production with age makes this especially relevant for older cancer patients. What’s still being worked out is exactly how therapeutic NO delivery can be optimized in clinical settings, and what the full long-term implications of chemo-related iNOS suppression are. This is not fringe science. The researchers publishing in this space are affiliated with the NIH, major university hospitals, and peer-reviewed journals. The question of how to protect and support immune function during and after chemotherapy is one of oncology’s most important ongoing conversations.
Chemotherapy is effective, but it doesn’t operate in a vacuum. It affects bone marrow, white blood cell production, and the molecular machinery that your immune system depends on, including the enzymes that produce nitric oxide. The good news is that there are evidence-based steps anyone can take to support NO production: eating a diet rich in leafy greens, beets, and nitrate-rich vegetables; staying physically active within the limits your treatment team sets; avoiding smoking; and exploring supplementation options in conversation with a doctor