NAC and Cancer Treatment: NAC may make Cancer Worse?

By Dr Frank Yap, MD - May 20, 2023

Highlights

Nutritional supplements and extracts like N-acetyl-l-cysteine have benefits and are used by cancer patients and those at-genetic risk of cancer. There is limited or hardly any clinical data available for use of nutritional supplements and foods in cancer patients. Generating clinical evidence of efficacy for cancer through a randomized clinical trial is further infeasible due to variations in genetics and cancer chemotherapy treatments across cancer patients. Hence a different and new approach is needed to find out for which cancers you should not take N-acetyl-l-cysteine supplement and why should not take them?

Is it okay to take N-acetyl-l-cysteine extracts or supplements for all cancer indications and any chemotherapy treatment? A common belief but a myth is that everything natural can only be of benefit and do no harm. For example, the use of grapefruit with certain medications is not recommended. Another example is the use of spinach with some blood thinning medications can cause adverse interactions and hence to be avoided. For cancer, nutrition including plant-based foods and supplements can influence outcomes and hence an extremely important decision which needs to be made. Hence NIH-National Cancer Institute has a website for nutrition for cancer care for patients which are generalized recommendations and not personalized for cancer indication and treatments.

A frequently asked question by cancer patients and those at-risk is “What Foods and Nutritional Supplements could be beneficial over others for me?”. “Who should not take an extract or supplement and why?”. Generic guidelines like eating only plant-based-foods or avoiding all sugar or adopting a keto diet is a good start but not actionable and personalized enough.

To find answers to questions on extracts and nutritional supplements and foods requires knowledge of contained active ingredients; genetic mutation prevalence for cancer indication; understanding of underlying cancer biology; chemotherapy treatments and mechanism of actions of active ingredients.

Taking N-acetyl-l-cysteine extracts or nutritional supplements may benefit Primary Penile Squamous Cell Carcinoma patients on Cisplatin treatment over Rooibos nutritional supplements. But N-acetyl-l-cysteine supplements or N-acetyl-l-cysteine extracts offer less benefit if on Radiation treatment for Primary Adamantinoma compared to Ecklonia Cava. Similarly, taking nutritional supplements N-acetyl-l-cysteine may benefit healthy individuals who are at genetic risk of cancer due to mutation of gene MYC over Coriander. But avoid nutritional supplements N-acetyl-l-cysteine when at genetic risk of cancer due to mutation of gene ATM.

The takeaway being – cancer, genomics, treatments and other personalized factors will influence decision making to questions like: Are extracts or nutritional supplements N-acetyl-l-cysteine beneficial and should not be taken? Why should N-acetyl-l-cysteine be not taken? Who should not take N-acetyl-l-cysteine? What are side effects of N-acetyl-l-cysteine with Radiation chemotherapy? What are the benefits of N-acetyl-l-cysteine for cancer? Can N-acetyl-l-cysteine help fight cancer and so on.

Whenever there are changes in chemotherapy treatments or cancer tissue genetics – the nutrition may change and hence needs to be re-evaluated. Do consider factors like cancer indication, ongoing chemotherapy treatments and nutritional supplements, age, gender, weight, height, lifestyle and genetics for personalization of nutrition.

Brief Overview

Use of nutritional supplements – vitamins, herbs, minerals, probiotics, and other specialty categories are increasing. Supplements are high concentrations of active ingredients which are also found in different foods. Difference between supplements and foods being that foods contain more than one active ingredient at much lower concentrations. Every active ingredient in an extract or nutritional supplement or food has a unique mechanism of action which can influence nutrition decisions.

These are some example questions which nutrition planning should help answer for you. Should you take supplements N-acetyl-l-cysteine? Should you take it when at genetic risk of cancer for mutation of gene MYC? Should you take it when at genetic risk of cancer for mutation of gene ATM? Should you take it when diagnosed with Primary Adamantinoma? Should you take it when diagnosed with Primary Penile Squamous Cell Carcinoma? Should you take it when on Cisplatin treatment? Should you continue taking it if you change your treatment from Cisplatin to Radiation? So a general explanation like – it is organic and plant-based or it increases immunity is not sufficient information for making a decision of use of N-acetyl-l-cysteine extracts and nutritional supplements.

Cancer

Genetic variations across cancer patients can be different and hence no two cancers are alike. The improved availability of “personalized to genetics” chemotherapy treatments and cancer disease monitoring via blood and saliva have been significant factors to improve outcomes. The earlier the lifestyle and treatment intervention – the better the influence on outcome. Genetic testing has the potential to assess cancer risk and susceptibility early. But for at-risk individuals besides regular monitoring in most cases there are no therapeutic treatment intervention options available. After diagnosis with cancer such as Primary Penile Squamous Cell Carcinoma or Primary Adamantinoma, the treatments get personalized to tumor genomics and factors like staging of disease, age and gender. During cancer remission (after treatment cycle is complete) – monitoring is used for assessment of any relapse and accordingly decide on next steps. A large majority of cancer patients and those at-risk may take nutritional supplements like N-acetyl-l-cysteine.

So the question is that are all genetic risks and cancer indications to be considered uniformly when making decisions on the use of N-acetyl-l-cysteine extracts or nutritional supplements? Are the biochemical pathway implications of genetic risk for cancer due to mutation of gene MYC the same as due to mutation of gene ATM? Are the implications of Primary Penile Squamous Cell Carcinoma the same as Primary Adamantinoma? Is it one and the same if you are on treatment with Radiation or Cisplatin?

N-acetyl-l-cysteine – An Extract or Nutritional Supplement

N-Acetyl L-cysteine (NAC) is a supplement form of the natural amino acid cysteine and a precursor which benefits in the formation of glutathione (antioxidant) in the body. Following are some of the potential health benefits of N-Acetyl L-cysteine (NAC) :

N-Acetyl L-cystein may be beneficial for reducing respiratory diseases such as COPD, asthma, bronchitis and cystic fibrosis (Claudio M Sanguinetti et al, Multidiscip Respir Med., 2016; Rabindra Tirouvanziam et al, Proc Natl Acad Sci U S A., 2006)
N-Acetyl L-cystein benefits may help reduce kidney damage (Vida Mokhtari et al, Cell J., 2017)
May improve brain health (Michael Costa et al, Chem Biol Interact., 2016)
May help improve liver health (Kívia Queiroz de Andrade et al, Int J Mol Sci., 2015; Vida Mokhtari et al, Cell J., 2017)
May help reduce symptoms of different psychiatric disorders (Brisa S Fernandes et al, J Clin Psychiatry., 2016; K Paydary et al, J Clin Pharm Ther., 2016)

N-acetyl-l-cysteine supplements contain many active ingredients including N-acetyl-l-cysteine at different concentration levels. The molecular pathways which are regulated by N-acetyl-l-cysteine include DNA Repair, Oxidative Stress and Cell Cycle. These biochemical pathways directly or indirectly regulate specific cancer molecular endpoints like growth, spread and death of cancer cells. Because of this biological regulation – for cancer nutrition, the right choice of supplements like N-acetyl-l-cysteine individually or in combination is an important decision to be made. When making decisions on the use of supplement N-acetyl-l-cysteine over other nutritional supplements – do consider all these factors.

Who Should not take N-acetyl-l-cysteine Supplements and Why?

There is no easy way to answer the question “For which cancers should I not chooseN-acetyl-l-cysteine nutritional supplements”. Just like the same chemotherapy treatment does not work across patients, for similar reasons N-acetyl-l-cysteine in comparison with other nutritional supplements may be beneficial or not. Along with which cancer and associated genetics – the ongoing treatments, lifestyle habits, height, weight and food allergies are all factors in deciding if N-acetyl-l-cysteine should be avoided or not and why.

1. Will N-acetyl-l-cysteine Supplements benefit Primary Adamantinoma patients undergoing Radiation treatment?

Primary Adamantinoma is characterized and driven by specific genetic mutations like ARHGAP45, PI4KB and SDSL leading to biochemical pathway changes in Oxidative Stress and Inositol Phosphate Signaling. A cancer treatment like Radiation works through a specific pathway mechanism of action. The goal is to have a good overlap between the treatment and cancer driving pathways for a personalized approach which is effective. In such a condition any food or nutritional supplement which has a contrary effect to the treatment or reduces the overlap should be avoided. As an example, N-acetyl-l-cysteine supplement should not be taken for Primary Adamantinoma along with treatment Radiation. N-acetyl-l-cysteine supplement impacts the biochemical pathway called Oxidative Stress which either promotes drivers of the disease and/or nullifies the treatment effect. Some of the factors which should be considered when choosing nutrition are type of cancer, treatments and supplements being taken currently (if any

2. Will N-acetyl-l-cysteine Supplements benefit Primary Penile Squamous Cell Carcinoma Patients undergoing Cisplatin Treatment?

Primary Penile Squamous Cell Carcinoma is characterized and driven by specific genetic mutations like ABRAXAS1, PIK3CB and NUP93 leading to biochemical pathway changes in DNA Repair, Hematopoiesis and Inositol Phosphate Signaling. A cancer treatment like Cisplatin works through specific pathway mechanisms. The goal is to have a good overlap between the treatment and cancer driving pathways for a personalized approach. In such a condition any food or nutritional supplement which supports treatment action or improves the overlap should be considered. As an example, N-acetyl-l-cysteine supplements should be considered for Primary Penile Squamous Cell Carcinoma along with the treatment Cisplatin. N-acetyl-l-cysteine supplement impacts pathways/processes like DNA Repair which either obstruct drivers of Primary Penile Squamous Cell Carcinoma and/or improve Cisplatin treatment effect.

3. What about N-acetyl-l-cysteine Supplements for Healthy Individuals with ATM Mutation associated Genetic Risk?

Different companies offer panels of genes to be tested for assessing genetic risk to different cancers. These panels cover genes associated with cancers of the breast, ovary, uterus, prostate, and gastrointestinal system and others. Genetic testing of these genes may confirm a diagnosis and help guide treatment and management decisions. Identification of a disease-causing variant may also guide testing and diagnosis of at-risk relatives. ATM is one of the genes generally available in panels for cancer risk testing.

ATM mutation causes biochemical pathways/processes like DNA Repair to get impacted. These pathways are direct or indirect drivers of cancer molecular endpoints. N-acetyl-l-cysteine should not be taken when the genetic panel identifies mutation of ATM for Chronic Myelomonocytic Leukemia. N-acetyl-l-cysteine impacts pathways/processes like DNA Repair and creates adverse conditions with ATM.

4. What about N-acetyl-l-cysteine Supplements for Healthy Individuals with MYC Mutation associated Genetic Risk?

MYC is one of the genes available in panels for cancer risk testing. MYC mutation causes biochemical pathways/processes like Cell Cycle, Antigen Presentation, PI3K-AKT-MTOR Signaling and Amino Acid Metabolism to get impacted. These pathways are direct or indirect drivers of cancer molecular endpoints. N-acetyl-l-cysteine supplements may be considered when the genetic panel identifies mutations in MYC for Burkitt Lymphoma. N-acetyl-l-cysteine impacts pathways/processes like Cell Cycle and creates a canceling effect in those individuals with MYC mutation.

* Other Factors are also included like BMI, Treatments, Lifestyle Habits

In Conclusion

It is important to remember that cancer chemotherapy treatments and nutrition are never the same for everyone. Food and nutritional supplements like N-acetyl-l-cysteine are chosen by you and can influence outcomes.

“What should I eat?” is a commonly asked question by cancer patients and those at-risk. The answer to this question depends on cancer indication, underlying genetics, current chemotherapy treatments, food allergies, lifestyle information, and food preferences.

What food you eat and which supplements you take is a decision you make. Your decision should include consideration of the cancer gene mutations, which cancer, ongoing treatments and supplements, any allergies, lifestyle information, weight, height and habits.

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