Which Antioxidants are Most Important for Cancer Treatment & Prevention

Source: Pixabay

Source: Pixabay

The role that vitamins and antioxidants (namely vitamin A, vitamin C, vitamin E, and their derivatives) play in a healthy diet is widely known: it is widespread across the media and has been backed by experts through decades of scientific research. [1][2][3]

Despite that, there is growing and convincing evidence that the consumption of high-dose dietary supplements increases the risk of some types of cancer. [1][4][5]

This is also true for patients receiving chemotherapy or radiation therapy, with studies reporting reduced survival rates in those who took supplemental antioxidants in conjunction with standard treatment. [6][7]

Cancer is a controversial and delicate topic that is deep-rooted in human conscience as a synonym for death, but thanks to the advancements in healthcare and oncology we could see a shift away from that notion in the future.

Every year the American Cancer Society publishes an article about the epidemiology related to cancer in the United States and makes estimations about the incidence, mortality, survival rate, and other trends for the coming year.

The report revealed that over 1.8 million new cancer cases and 600 thousand deaths are expected to occur for the year 2021 in the US alone. Considering those numbers, it is predicted that most new cases will be for prostate (26% of males) and breast cancer (30% of females), followed by lung/bronchus (12-13%) and colon/rectum cancer (8%).

Concerning survival rate, thanks to an early diagnosis and notable improvements in cancer therapy the overall drop in mortality between 1991 and 2018 was 31%. [8]

The history behind vegetables, fruits and antioxidants in cancer research

These lifesaving advancements are sustained by research, with multiple medications being tested in order to measure their usefulness in treatment or prevention. The formal relationship between antioxidants and cancer began when cumulative epidemiological evidence from over four decades ago was analyzed.

 An article published by the journal Nutrition and Cancer in 1992 examined 170 epidemiological studies and found that 132 strongly suggested fruits and vegetables intake had a preventive effect on cancer.

Only six studies proposed they could be harmful, distributed as one for stomach cancer, three for colorectal cancer, and two for prostate cancer. [2] The National Cancer Institute promoted the consumption of vegetables and fruits through the “5 A Day” program during the 1990s to encourage people in the US to eat at least 5 servings per day. [9]

In parallel, the search for the specific substance responsible for the protective effect began and the starting point was a group of molecules abundant in fruits and vegetables: antioxidants.

Throughout the 1980s-1990s, the American multicenter double-blind, randomized, placebo-controlled Beta-Carotene and Retinol Efficacy Trial (CARET) investigated the link between high doses of beta-carotene/retinol and cancer prevention.

Two groups were studied: heavy smokers and workers exposed to asbestos, who were randomly assigned to receive either treatment or placebo. During a report in 1993, the project expected a 23% reduction by 1998 when the study was set to finish. [10]

However, in 1996, the trial was stopped because the incidence of lung cancer and mortality rate increased by 28% and 17% respectively for the active-treatment group in comparison to the placebo group. [4]

The sudden appearance of lung cancer within a couple of years after beginning treatment suggests that patients had preclinical tumors, and their growth was accelerated by beta-carotene and retinol. This is supported by a CARET follow-up study that was published six years later where, after stopping the supplements, the incidence for lung cancer decreased from 28% to 12% which remains high but no longer statistically significant. [11]

The Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study Group (ATBC) trial from Finland reached a similar conclusion in 1994, concluding that beta-carotene increased the incidence of lung cancer by 18% in comparison to the other groups studied. [12]

In 2004, the Supplémentation en Vitamines et Minéraux Antioxydants (SUVIMAX) study performed in France was reported.

The results showed that a combination of vitamin C, vitamin E, beta-carotene, selenium, and zinc in low doses showed a protective effect against cancer in men, [13] which disappeared after 5 years of discontinuing the treatment. [14]

The Selenium and Vitamin E Cancer Prevention Trial (SELECT) reported in 2010 a statistically significant risk increase for developing prostate cancer in the group that received high daily doses of vitamin E alone. [5]

Antioxidants can be damaging during chemotherapy treatment too, as announced by Ambrosone CB, et. al. in 2019. In their study, the intake of any antioxidant supplements before and during chemotherapy increased the risk of recurrence and death for breast cancer. [7] Thus the antioxidant conundrum persists: what is behind these seemingly contradicting results?


Know Your Risk

Is taking antioxidant supplements good or bad for cancer prevention?

A widely known mechanism for cancer development consists of DNA damage caused by reactive oxygen species (ROS) through a process called oxidative stress.

ROS are free radicals, they are toxic molecules produced by cellular metabolism, and they are capable of causing mutations in the DNA. If this damage is not repaired in time, the mutation is passed to future cell generations, promoting the development and spread of cancer.

Antioxidants can donate electrons to free radicals, reducing them and as a consequence blocking their toxicity. However, carcinogenic cells can be affected and destroyed by free radicals too, [1] so the protective effect of antioxidants can benefit cancer propagation as reported by Davison CA, et. al. in 2013.

Cancer cells detached from the extracellular matrix face a dangerous increase in ROS, usually preventing cancer from spreading to other tissues; this process is known as metastasis. Their study discovered that breast cancer cells were protected by antioxidant enzymes, namely catalase and superoxide dismutase, both in vitro and in vivo. [15]

A study published two years later found similar results with N-acetylcysteine and vitamin E in mice, increasing the number of lymph nodes affected by metastasis of melanoma. [16]

The repercussion of these findings was a definitive shift away from the supplemental intake of high-dose antioxidants for cancer prevention and treatment coadjuvant.

The general conclusion is that nutrients contained in fruits and vegetables act together: rather than requiring extremely high doses of a couple of antioxidants (which was the premise most supplemental antioxidant trials were designed around), [4][5][10][11][12] we need an optimal physiological concentration of combined antioxidants, usually achievable through a healthy diet [2] or low dose multivitamin supplements [14].

Ironically, this had been hypothesized almost thirty years ago by Block G, et. al. in the journal Nutrition and Cancer. [2]

The latest evidence on cruciferous vegetables and cancer prevention

In recent years, the group of cruciferous vegetables (broccoli, Brussels sprouts, cauliflower, cabbage, bok choy, etc.) have gained recognition for having anti-tumorigenic properties thanks to being enriched with glucosinolates precursors, capable of regulating genetic processes responsible for cancer development. [17]

A few meta-analyses have studied this proposition during the last decade, reporting suggestive positive effects for cruciferous vegetables intake in pancreatic, [18] colorectal [19], and breast cancer [20].

However, the data is not conclusive and there is a limited number of studies, therefore more research is required in this field before reaching an optimal interpretation. Despite this, the World Cancer Research Fund and the American Institute for Cancer Research recommend eating at least 20 to 24 grams per day of non-starchy vegetables, which include cruciferous vegetables, as part of a healthy diet. [1]


The perfect diet is based on your needs

Source: Pixabay

Source: Pixabay

Examples of commonly used antioxidants: [1]

  • Carotenoids: derivatives of vitamin A found in carrots, tomatoes, spinach, pumpkin, red peppers, and others. Beta-carotene is a carotenoid found in oranges, carrots, spinach, lettuce, tomatoes, broccoli, etc.

  • Vitamin A: or retinol, is found in the liver, eggs, and dairy products.

  • Alpha-tocopherol: a form of vitamin E found in palm, sunflower, corn, soya bean and olive oils, nuts, whole grains, fish, green and leafy vegetables, etc.

  • Vitamin C: or ascorbic acid, can be found in vegetables, tubers, and fruits such as kiwi fruit, papaya, citrus fruit, strawberries, etc.

Evidence for antioxidant intake in different types of cancer, according to the Continuous Update Project (CUP) Expert Report 2018: [1]

Prostate cancer:

  • Dietary beta-carotene intake

    • Evidence: strong.

    • Conclusion: no significant effect on risk or prevention. Foods and high-dose supplements (20 to 50 mg per day) containing beta-carotene are unlikely to represent a risk for prostate cancer.

  • Low plasma alpha-tocopherol (vitamin E) concentration:

    • Evidence: limited.

    • Conclusion: suggestive increased risk of prostate cancer.

Breast Cancer:

  • Foods containing carotenoids

    • Evidence: limited.

    • Conclusion: suggestive decreased risk of unspecified breast cancer.

  • Non-starchy vegetables

    • Evidence: limited.

    • Conclusion: suggestive 21% decreased risk in estrogen receptor-negative breast cancer with greater consumption.

Lung Cancer:

  • High-dose beta-carotene supplements

    • Evidence: strong.

    • Conclusion: convincing data for 17-28% increased risk of developing lung cancer in people with a past or present history of smoking.

  • Foods containing carotenoids

    • Evidence: limited.

    • Conclusion: suggestive 2% decreased risk with greater consumption.

  • Dietary retinol intake

    • Evidence: limited.

    • Conclusion: suggestive 0-3% decreased risk with greater consumption.

  • Foods containing vitamin C

    • Evidence: limited.

    • Conclusion: consistent evidence suggesting a 13% decrease in risk for current smokers.

  • Fruits

    • Evidence: limited.

    • Conclusion: suggestive decrease of 9% in current smokers and 3% in people with a history of smoking with greater consumption.

Skin Cancer:

  • High-dose beta-carotene supplements

    • Evidence: limited.

    • Conclusion: suggestive 6% decreased risk for developing colorectal cancer with greater consumption.

  • Non-starchy vegetables

    • Evidence: limited.

    • Conclusion: suggestive 8% increased risk of developing colorectal cancer with low consumption.

  • Fruits

    • Evidence: limited.

    • Conclusion: suggestive 7% increased risk of developing colorectal cancer with low consumption.

Colorectal Cancer:

  • Vitamin C

    • Evidence: limited.

    • Conclusion: suggestive 6% decreased risk for developing colorectal cancer with greater consumption.

  • Non-starchy vegetables

    • Evidence: limited.

    • Conclusion: suggestive 8% increased risk of developing colorectal cancer with low consumption.

  • Fruits:

    • Evidence: limited.

    • Conclusion: suggestive 7% increased risk of developing colorectal cancer with low consumption.

Cancer research is a complex topic that is constantly misunderstood and miscommunicated through the media. Each patient requires a diet crafted to meet their metabolic and genetic needs, taking into account chemotherapy or radiotherapy in each given case. As evidence grows stronger, we will be able to make the best-informed decisions towards a healthy diet for our patients: prevention begins at home.


Know Your Risk

 


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Diseases, Cancer Prevention, cancer, Food and DietPreventive Medicine & Cancer Carepreventive medicine, cancer prevention, food and diet