Supplements

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Supplment Overview

Nutritional supplements have the potential to complement cancer treatment by supporting overall health, enhancing treatment efficacy, and possibly improving survival outcomes. Supplements such as omega-3 fatty acids, vitamin D, selenium, and ginseng have shown promise in reducing inflammation, boosting immune responses, inhibiting tumor growth, and improving quality of life. For example, omega-3s have been linked to prolonged survival and reduced recurrence in certain cancers, while vitamin D has demonstrated benefits in reducing advanced cancer risks and mortality in individuals with normal body weight. Selenium and ginseng have exhibited tumor-modulating properties and improved survival in specific cancer types, particularly in individuals with deficiencies. Additionally, multivitamins and folate can help address malnutrition, a common issue in cancer patients, which may indirectly support better treatment outcomes. However, while these supplements hold promise, their effectiveness varies by cancer type, dosage, and individual health status, underscoring the importance of personalized approaches and consultation with healthcare providers.

Fish Oil (Omega-3 Fatty Acids)

Fish oil, rich in omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), has shown promise in cancer prevention and survivorship due to its anti-inflammatory and tumor-modulating properties. Numerous studies have demonstrated that omega-3 fatty acids can inhibit tumor growth, enhance immune responses, and induce cancer cell death. A meta-analysis of 25 studies found that higher omega-3 PUFA intake was associated with a 17% reduced risk of digestive system cancers (RR: 0.83; 95% CI: 0.76–0.91). Similarly, in breast cancer patients, marine omega-3 intake was linked to a 14% reduction in risk (RR: 0.86; 95% CI: 0.78–0.94). Clinical trials have also highlighted improvements in outcomes such as progression-free survival and overall survival, with significant benefits observed in metastatic breast cancer and stage IIIB colorectal cancer patients who received omega-3 supplementation. For instance, DHA incorporation was shown to prolong survival from 18 to 34 months in metastatic breast cancer patients, while EPA supplementation increased survival in pancreatic cancer from 4.1 to 6.8 months.

Despite its potential, the evidence on fish oil’s role in cancer treatment remains mixed, with some studies reporting null effects or even slight risks in specific contexts. For example, a large randomized controlled trial with over 25,000 participants found no significant reduction in overall cancer incidence (HR: 1.03; 95% CI: 0.93–1.13) or mortality (HR: 0.97; 95% CI: 0.79–1.20) with omega-3 supplementation. Additionally, poor manufacturing practices and contamination risks, such as heavy metals in fish oil supplements, warrant caution. However, the overall consensus is that fish oil is safe for most individuals at recommended doses and may offer significant benefits for cancer patients when used as part of a broader treatment plan. Personalized approaches, such as monitoring omega-3 incorporation into plasma or tumor tissues, could help optimize its therapeutic potential and improve outcomes in cancer care.

Citations:

1. Zhao Y, Tian Q, Cheng X, et al. Omega-3 PUFA intake and the risk of digestive system cancers: A meta-analysis. Medicine (Baltimore). 2021.
2. Zheng JS, Hu XJ, Zhao YM, et al. Intake of fish and marine n-3 polyunsaturated fatty acids and risk of breast cancer: meta-analysis of data from 21 independent prospective cohort studies. BMJ. 2013.
3. Bougnoux P, Hajjaji N, Couet C, et al. DHA incorporation into plasma and survival outcomes in metastatic breast cancer patients. Cancers. 2021.
4. Manson JE, Cook NR, Lee IM, et al. Marine omega-3 fatty acids and prevention of cardiovascular disease and cancer. New England Journal of Medicine. 2019.
5. Wigmore SJ, Ross JA, Falconer JS, et al. The effect of EPA supplementation on survival in pancreatic cancer. Nutritional Cancer. 2000.

Folate (vitamin B9)

Folate (vitamin B9) plays a dual role in cancer biology, with its effects varying based on individual factors, dosage, and timing of supplementation. Observational studies suggest a protective effect of dietary folate intake in certain cancers, such as esophageal squamous cell carcinoma, where higher intake was associated with a significant reduction in cancer-specific mortality (HR: 0.41; 95% CI: 0.25–0.69). Folate deficiency has also been linked to increased risks for some cancers, as it may impair DNA synthesis and repair. However, synthetic folic acid supplementation, commonly found in multivitamins and fortified foods, has shown inconsistent and sometimes concerning results. For example, a meta-analysis reported a marginal increase in overall cancer incidence (RR: 1.07; 95% CI: 1.00–1.14) and a significant 24% increase in prostate cancer incidence associated with folic acid supplementation (RR: 1.24; 95% CI: 1.03–1.49).

Conversely, excessive folic acid intake has been linked to potential tumor-promoting effects in certain cancers. For instance, among patients with non-muscle-invasive bladder cancer, higher synthetic folic acid intake was associated with increased recurrence risk (HR: 1.80; 95% CI: 1.14–2.84). Similarly, trials investigating folic acid’s role in combination with other B vitamins found no significant reduction in cancer risk and, in some cases, a slight increase in recurrence rates. These findings raise concerns about the widespread use of folic acid supplementation, especially in individuals with adequate dietary intake, as folic acid intake from multivitamins and fortified foods can exceed recommended levels. While dietary folate appears beneficial in certain contexts, caution is warranted regarding synthetic folic acid supplementation, particularly in cancer patients or those at risk for recurrence.

Citations:

1. Yang W, Yang Z, Yu H, et al. Dietary factors and risk of mortality among patients with esophageal cancer: a systematic review. BMC Cancer. 2020.
2. Kim Y-I. Folate and cancer: a tale of Dr. Jekyll and Mr. Hyde? American Journal of Clinical Nutrition. 2018.
3. Vollset SE, Clarke R, Lewington S, et al. Cancer risk with folic acid supplements: a systematic review and meta-analysis. BMJ Open. 2011.
4. Mason JB, Dickstein A, Jacques PF, et al. Is folic acid safe for non–muscle-invasive bladder cancer patients? American Journal of Clinical Nutrition. 2018.

Multivitamins

The role of multivitamin use in cancer treatment and survivorship is complex, with studies showing largely neutral or marginal benefits, particularly in specific populations. For instance, findings from the CALGB 89803 trial involving patients with stage III colon cancer revealed no significant association between multivitamin use and improved disease-free survival (HR: 0.94; 95% CI: 0.77-1.15) or overall survival (HR: 0.92; 95% CI: 0.74-1.16). Similarly, in the Life After Cancer Epidemiology (LACE) study, multivitamin use among women with early-stage breast cancer did not significantly influence recurrence (HR: 0.92; 95% CI: 0.71-1.20) or total mortality (HR: 0.92; 95% CI: 0.71-1.19). However, persistent multivitamin use combined with other healthy lifestyle factors, such as a high intake of fruits and vegetables and regular physical activity, showed improved overall survival, suggesting that multivitamin benefits may be part of a broader holistic approach to survivorship care.

While multivitamin use appears to offer minimal direct benefit for cancer recurrence or survival, some studies hint at modest protective effects when combined with specific nutrients or antioxidants. For example, the After Breast Cancer Pooling Project found that antioxidant supplements, such as vitamin C and E, were associated with reduced risk of death (RR for vitamin C: 0.81; 95% CI: 0.72-0.92), although these effects were attenuated when analyzed in combination with multivitamins. The Women’s Health Initiative, a large-scale cohort study, reported no significant associations between multivitamin use and cancer risk across multiple types, including breast, colorectal, and lung cancers, over an average of eight years of follow-up. These findings suggest that while multivitamins may not directly influence cancer outcomes, they could help address deficiencies commonly observed in malnourished patients, potentially supporting overall health during cancer treatment.

Citations:

1. Ng K, Meyerhardt JA, Chan JA, et al. Multivitamin Use Is Not Associated With Cancer Recurrence or Survival in Patients With Stage III Colon Cancer. Journal of Clinical Oncology. 2010.
2. Kwan ML, Greenlee H, Lee VS, et al. Multivitamin Use and Breast Cancer Outcomes in Women with Early-Stage Breast Cancer: The LACE Study. Breast Cancer Research and Treatment. 2011.
3. Nechuta S, Lu W, Chen Z, et al. Post-diagnosis supplement use and breast cancer prognosis in the After Breast Cancer Pooling Project. Cancer Epidemiology, Biomarkers & Prevention. 2013.
4. Mursu J, Robien K, Harnack LJ, et al. Multivitamin Use and Risk of Cancer and Cardiovascular Disease in the Women’s Health Initiative Cohorts. Archives of Internal Medicine. 2009.

Vitamin D

Vitamin D has been widely studied for its potential role in cancer prevention and treatment, with evidence suggesting both benefits and limitations. A secondary analysis of the VITAL Randomized Clinical Trial (2020) found that vitamin D3 supplementation (2000 IU/day) significantly reduced the risk of advanced (metastatic or fatal) cancer among individuals with normal body weight (HR, 0.62; 95% CI, 0.45-0.86), though no benefits were observed for those who were overweight or obese. Interestingly, the risk reduction was not tied to baseline vitamin D deficiency, highlighting the complexity of its role in cancer prevention. Meta-analyses also support the link between higher circulating vitamin D levels and reduced cancer mortality, with a 12% reduction in cancer-related deaths (RR, 0.88; 95% CI, 0.79-0.96) but no significant effect on overall cancer incidence (Annals of Oncology, 2019). Despite these promising findings, the impact of vitamin D appears to vary depending on cancer type, with benefits observed for colorectal and breast cancers, but mixed or detrimental associations reported for prostate and pancreatic cancers.

The mechanisms behind vitamin D’s influence on cancer outcomes are thought to involve its effects on cell differentiation, proliferation, apoptosis, and angiogenesis. However, results from clinical trials remain inconsistent, with some studies finding no significant survival benefit from supplementation. For example, the AMATERASU trial (2019) reported no improvement in relapse-free survival among digestive tract cancer patients, except in those with moderate baseline vitamin D levels (HR, 0.46; 95% CI, 0.24-0.86). Additionally, concerns about potential biases in some studies and the variability of results across cancer types highlight the need for further research. While vitamin D shows promise in reducing cancer mortality and improving outcomes for specific cancers, its optimal dosage, target populations, and long-term safety require additional investigation to confirm its role as a therapeutic supplement in cancer care.

Citations:

1. Chandler PD, Chen WY, Ajala ON, et al. Effect of Vitamin D3 Supplements on Development of Advanced Cancer: A Secondary Analysis of the VITAL Randomized Clinical Trial. JAMA Network Open. 2020.
2. Keum N, Giovannucci E. Vitamin D supplements and cancer incidence and mortality: a meta-analysis. British Journal of Cancer. 2014.
3. Maalmi H, Walter V, Jansen L, et al. Association between blood 25-hydroxyvitamin D levels and survival in colorectal cancer patients. International Journal of Cancer. 2018.
4. Urashima M, Ohdaira H, Akutsu T, et al. Effect of Vitamin D Supplementation on Relapse-Free Survival Among Patients With Digestive Tract Cancers: The AMATERASU Randomized Clinical Trial. JAMA. 2019.

Selenium

Selenium, an essential trace mineral, has been studied for its potential role in cancer prevention and treatment, but the findings remain mixed and context-dependent. Selenium supplementation appears to benefit certain cancers, particularly in individuals with low baseline selenium levels. For example, studies suggest that higher serum selenium levels are associated with improved survival in breast cancer (HR for mortality: 0.63; 95% CI: 0.44–0.89) and better outcomes in stage I lung cancer (HR: 2.73 for low selenium levels, P=0.01) compared to higher levels. Similarly, selenium levels above 70 μg/L were linked to improved outcomes in laryngeal cancer, and supplementation demonstrated protective effects against chemotherapy-induced toxicity in preclinical models. However, the positive effects are often limited to specific populations, such as those with selenium deficiencies, and evidence for prevention or treatment efficacy in broader populations remains inconclusive.

On the other hand, selenium supplementation may pose risks in certain scenarios, especially for individuals with sufficient baseline selenium levels. High selenium intake has been associated with increased risks of prostate cancer mortality (HR for 140+ μg/day: 2.60; 95% CI: 1.44–4.70) and nonmelanoma skin cancer (HR for squamous cell carcinoma: 1.25; 95% CI: 1.03–1.51). Meta-analyses, such as a 2018 Cochrane review, found no significant reduction in overall cancer incidence (RR: 0.99; 95% CI: 0.86–1.14) or mortality (RR: 0.81; 95% CI: 0.49–1.32) with selenium supplementation in broader populations. These results suggest that while selenium may benefit specific cancers or individuals with deficiencies, indiscriminate supplementation could lead to harm, highlighting the importance of personalizing selenium use in cancer care based on baseline levels and cancer type.

Citations:

1. Vinceti M, Filippini T, Rothman KJ. Selenium for preventing cancer. Cochrane Database of Systematic Reviews. 2018.
2. Kristal AR, Darke AK, Morris JS, et al. Selenium supplementation and prostate cancer mortality. JNCI Journal of the National Cancer Institute. 2014.
3. Hughes DJ, Duarte-Salles T, Hybsier S, et al. Serum selenium levels predict survival after breast cancer. International Journal of Cancer. 2018.
4. Rayman MP, Winther KH, Pastor-Barriuso R, et al. Optimising selenium for modulation of cancer treatments. Anticancer Research. 2017.
5. Goodman GE, Thornquist MD, Balmes J, et al. Phase III chemoprevention trial of selenium in NSCLC patients. Journal of Clinical Oncology. 2013.

Ginseng

Ginseng, a traditional herbal remedy widely used in East Asian medicine, has shown potential benefits in cancer prevention and treatment, particularly in improving survival rates and quality of life for patients. The Shanghai Breast Cancer Study found that women with breast cancer who used ginseng had significantly reduced risks of total mortality (HR: 0.71; 95% CI: 0.52-0.98) and disease-specific mortality/recurrence (HR: 0.70; 95% CI: 0.53-0.93) compared with non-users. Additionally, a prospective cohort study of 6,282 individuals aged 55 or older showed reduced all-cause mortality among male ginseng users (HR: 0.90; 95% CI: 0.81-0.99), although cancer-specific mortality reduction was not statistically significant. For female users, cancer-specific mortality was numerically lower (HR: 0.80; 95% CI: 0.60-1.08), suggesting potential sex-specific effects. These findings highlight ginseng’s promise in enhancing survival, though additional studies are needed to confirm its efficacy across broader populations.

The anticancer properties of ginseng are believed to stem from bioactive compounds like ginsenosides, particularly G-Rh2, which have demonstrated antitumor effects across various cancer types in preclinical studies. Ginsenosides exhibit multiple mechanisms of action, including reducing inflammation, inhibiting tumor cell growth, inducing apoptosis, and enhancing the immune response. While most evidence comes from in vitro and in vivo studies, these findings suggest that ginseng and its metabolites could complement existing therapies, particularly when combined with chemotherapy. However, further clinical trials are essential to establish standardized doses, long-term safety, and its efficacy in different cancers. As a low-risk supplement with potential benefits, ginseng remains a popular choice for cancer patients seeking complementary treatment options.

Citations:

Ginseng and Cancer. Cancer Therapy Advisor. 2021.

Chen Z, Gu K, Zheng Y, et al. Association of Ginseng Use with Survival and Quality of Life among Breast Cancer Patients. American Journal of Epidemiology. 2006.

Zheng XY, Zhao YY, et al. Ginseng and Anticancer Drug Combination to Improve Cancer Chemotherapy: A Critical Review. Processes. 2021.

Zhang M, Huang J, Xie X, et al. Anti-Cancer Effect of Panax Ginseng and Its Metabolites: From Traditional Medicine to Modern Drug Discovery. MDPI Processes. 2021.

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