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Health Protocols

Cancer Radiation Therapy

Natural Interventions For Improving Radiation Sensitivity

This section summarizes data identifying radioprotective properties of a variety of natural compounds. Table 1, later in this section, summarizes human data on specific natural interventions shown to improve outcomes when used along with radiotherapy.

Curcumin is extracted from the spice turmeric (Curcuma longa) and has been extensively studied for its radiosensitizing properties (Verma 2016). In laboratory studies, curcumin sensitized multiple types of cancer cells to radiation (Qiao 2013). In prostate cancer cell lines, curcumin was a potent radiosensitizer that overcame the effects of radiation-induced pro-survival gene expression (Chendil 2004). In head and neck squamous cell cancer cell lines, curcumin arrested cells in the mitosis phase of cell division, which is the phase where cells are most susceptible to the effects of radiation (Wilken 2011). In colorectal cancer cell lines, curcumin led to an improved antitumor effect by blocking the pro-survival protein complex nuclear factor kappa B (NF-κB) that may be responsible for radioresistance (Sandur 2009). Similarly, in breast cancer cell lines, curcumin blocked NF-κB and was able to overcome hypoxia, thus sensitizing breast cancer cells to the antitumor effect of radiation (Aravindan 2013).

Resveratrol, found in grapes, blueberries, red wine and Japanese knotweed, among other plant sources, is a polyphenol with anti-inflammatory properties. Resveratrol has been shown to control cell proliferation, angiogenesis, and cancer cell death (Borriello 2014; Kma 2013; Dobrzynska 2013). In a cell-line study in radioresistant melanoma cells, resveratrol enhanced radiosensitivity, reduced proliferation, and increased cell death (Fang 2013). A similar effect was observed in a study of a radioresistant prostate cancer cell line treated with resveratrol and radiation (Fang 2012). Other similar cell-line studies have confirmed favorable radiosensitizing effects with the addition of resveratrol (Dobrzynska 2013; Kma 2013; Luo 2013; Tan 2017).

A study was performed in which mice were injected with glioblastoma multiforme cells. This type of brain cancer is inherently resistant to radiation. Results showed the glioblastoma cells pretreated with resveratrol were more sensitive to radiation. The tumors that formed were smaller than those formed from cells that were not pretreated. The mice receiving the cells pretreated with resveratrol survived longer (Yang 2012; Kma 2013). This result was confirmed in a more recent study (Wang, Long 2015).

The marker CD133 has been used extensively to identify cancer stem cells, which are very resistant to treatment with radiation therapy (Wu 2009). A study in which mice were injected with resveratrol-treated CD133-positive atypical teratoid/rhabdoid cells (a rare type of tumor) in combination with radiation showed enhanced survival in mice. Researchers concluded that resveratrol was an effective radiosensitizer in this radioresistant form of cancer (Kao 2009). In a separate study, researchers found decreased CD133 expression in radioresistant glioblastoma cells treated with resveratrol (Wang, Long 2015).

Quercetin is a flavonoid from plants with radiosensitizing effects in medulloblastoma, breast, cervical, and colorectal cancer cell lines (Lagerweij 2016; Malik 2016). In a mouse study on colorectal cancer, tumor growth was significantly slowed in mice treated with quercetin, and the DNA repair mechanism was compromised in tumor cells (Lin 2012).

Genistein is an isoflavone from soy that enhanced the effects of radiation in prostate, cervical, and estrogen receptor-positive and estrogen receptor-negative breast cancer cell line studies (Mahmoud 2014; Liu 2013; Zhang 2006; Malik 2016). Genistein inhibited growth of colon cancer cells when combined with radiation by decreasing epidermal growth factor receptor (EGFR) activation. EGFR activation results in multiple signaling cascades related to cancer cell growth and metastasis, and overactive EGFR is associated with a worse prognosis (Gruca 2014).

A constituent from the plant Panax ginseng sensitized non-small cell lung cancer cells to radiation (Wang, Li 2015), while a Panax ginseng extract protected against radiation-induced liver injury (Kim 2017). Zerumbone, a constituent of ginger (Zingiber officinale), sensitized colorectal cancer cells to radiation (Deorukhkar 2015).

Ashwagandha (Withania somnifera) is a plant with anti-inflammatory, immune-modulating, anti-stress, and antitumor effects (Winters 2006; Marlow 2017; Lee 2016; Wadhwa 2016). Ashwagandha acted as a radiosensitizer in studies in renal cancer, melanoma, and lymphoma cell lines (Yang 2011b; Kalthur 2010; Yang 2011a; Abdallah 2016). In a study of mice bearing melanoma tumors, there was an at least 50% decrease in tumor size in 62.5% of the animals after treatment with radiation therapy, ashwagandha (15 mg/kg injected five days/week for three weeks), and local hyperthermia (Kalthur 2010). In another rodent study, radioresistant mouse melanoma cells or radiosensitive fibrosarcoma cells were implanted into mice. The mice were then treated with a combination of radiation, hyperthermia, and ashwagandha (40 mg/kg) one hour before radiation. A complete response was seen in 37% of mice with melanoma and 64% with fibrosarcoma. A complete response was defined as tumor regression with no regrowth at the site of the primary tumor for 120 days (Uma Devi 2003). These results are particularly encouraging because of the high rate of radioresistance in melanomas (Kalthur 2010).

An increasing number of studies have investigated the relationship between vitamin D3 levels and vitamin D receptor gene abnormalities and certain cancers, including colorectal, breast, and other cancers (Ordonez Mena 2014). Vitamin D3 has also been studied for its radiosensitizing properties. Vitamin D3 radiosensitized breast cancer cells intrinsically resistant to radiation (Bristol 2012; Wilson 2011), non-small cell lung cancer cells (Sharma 2014), and colorectal cancer cells (Sharma 2014; Findlay 2014). One proposed mechanism for this effect is a process called autophagy, in which the cell degrades its own contents to generate energy and metabolic precursors in response to stress (Bristol 2012; Sharma 2014; Gewirtz 2007). In an aggressive breast (Mineva 2009) and prostate tumor cell line (Xu 2007), vitamin D3 improved radiosensitivity by decreasing gene expression of RELB, a gene that promotes survival in tumor cells by protecting them from radiation.

Epigallocatechin gallate (EGCG) is a component of green tea. A study was conducted on the effects of EGCG during radiation in 10 patients with locally advanced breast cancer. Five patients received 400 mg EGCG three times daily plus radiotherapy, and five received radiotherapy alone. Patients taking EGCG had lower serum levels of VEGF, hepatocyte growth factor (HGF), and metalloproteinases 2 and 9 (MMP-2/MMP-9), all factors associated with tumor progression and metastasis. Serum from patients taking EGCG was applied to cells from a highly metastatic breast cancer cell line. The serum decreased the proliferation of the cancer cells, increased apoptosis, and reduced activation of proteins involved in resistance to radiation (Zhang 2012). Another study examined the effects of EGCG on radiosensitization of human brain microvascular endothelial cells. Vascular endothelial cells are important in the formation of blood vessels by the tumor. In cells treated with EGCG and radiation, cell death was 5-fold higher than in cells treated with radiation alone (McLaughlin 2006).

Sulforaphane is a plant chemical found in broccoli (Brassica oleracea) and other cruciferous vegetables (eg, Brussels sprouts, cabbage, and cauliflower) (Kotowski 2011; Higdon 2016). When head and neck cancer cells were treated with sulforaphane and then irradiated, researchers observed that the combined therapy resulted in a stronger inhibition of cell proliferation than either treatment alone (Kotowski 2011). Additionally, sulforaphane enhanced the radiosensitivity of mouse osteosarcoma cells (Sawai 2013).

Cell line studies have found that eicosapentaenoic acid (EPA), an omega-3 fatty acid from fish and fish oil, sensitizes colorectal cancer and glioblastoma cells to radiation (Manda 2011; Benais-Pont 2006). Omega-3 fatty acids, particularly EPA and docosahexaenoic acid (DHA), have been shown to benefit people undergoing radiotherapy or chemotherapy, primarily by preserving body composition (de Aguiar Pastore Silva 2015).

A randomized controlled trial of Boswellia serrata extract in 44 patients receiving radiation for brain tumors found, on MRI examination, that the largest tumor of those in the Boswelliagroup was reduced in size by 88% after radiotherapy, while the largest tumor shrank by only 19% in the placebo group (Kirste 2011). Polysaccharide K (PSK), derived from the mushroom Coriolus versicolor, has been used in traditional Chinese medicine for hundreds of years (Standish 2008). A review of scientific research showed PSK in combination with standard radiation and chemotherapy for lung cancer prolonged survival, reduced tumor-related symptoms, and improved immune function (Fritz 2015). In a study of 187 patients with esophageal squamous cell carcinoma, 5-year survival was assessed for different treatment regimens: radiation therapy (40% survival), radiation therapy with PSK (42%), radiation therapy with chemotherapy (29%), or radiation therapy with chemotherapy and PSK (37%) (Ogoshi 1995). In another study, 90 patients with cervical cancer were treated with either radiation and 3 grams PSK or radiation alone. Sixty percent of patients in the PSK group had a response rated as “good,” but only 32% of the control group had a good response. Additionally, the PSK group had better immune system response throughout treatment (Kazuta 1985; Fritz 2015).

Radiation depletes nutrients such as pyridoxine (vitamin B6), and administration of pyridoxine can reverse the deficiency without side effects. A study in 210 women with stage II endometrial cancer randomized to receive 300 mg pyridoxine daily or no pyridoxine during radiation therapy showed 15% improved 5-year survival and improved tolerance to radiation in those taking pyridoxine. Improvements in nausea, vomiting, and diarrhea were also noted (Ladner 1988).


Table 1: Natural Agents Shown to Improve Radiotherapy Outcomes

Cancer Type

Natural Agent

Human Data

Lung

 

 

Astragalus (Astragalus membranaceus)

He 2013 – A meta-analysis including 29 randomized controlled trials on astragalus-based Chinese herbal medicine preparations in combination with radiotherapy for non-small cell lung cancer. Several of these studies showed reduced risk of death at up to three years. Twenty-six studies revealed enhanced tumor response. Multiple studies showed improved quality of life and amelioration of some radiotherapy side effects.

Alpha tocopherol (a form of vitamin E) plus pentoxifylline (a drug)

Misirlioglu 2006 – Sixty-six patients were randomized to receive either radiation alone (one group) or radiation together with 400 mg pentoxifylline three times daily and 300 mg alpha-tocopherol twice daily (the second group). One-year overall survival was 55% in the study group and 40% in the control group. Two-year survival was 30% in the study group and 14% in the control group. Progression-free survival rates also improved in the study group. Smokers should not take alpha-tocopherol during radiation therapy, as it can lead to worse outcomes (Meyer 2008).

Polysaccharide K (PSK)

Fritz 2015 – A review of the scientific literature on PSK combined with radiotherapy and chemotherapy showed improved 1-, 2-, and 5-year survival rates; improved immune function and blood cell function; and decreased fatigue, loss of appetite, and body weight.

Cervical

 

Polysaccharide K (PSK)

Kazuta 1985 – Ninety patients treated for cervical cancer received either 3 grams PSK with radiation therapy or radiation alone. Sixty percent of patients in the PSK group had a response rated as “good,” but only 32% of the control group had a good response.

Vitamin A

Basu 2016 – Several studies that examined interferon-alpha and retinoic acid (vitamin A) in combination with radiotherapy for the treatment of cervical cancer have found a better response to radiation in combination with interferon-alpha and retinoic acid than to radiation alone.

Esophageal

Polysaccharide K (PSK)

Ogoshi 1995 – Patients were randomly assigned to receive different therapies for esophageal squamous cell carcinoma and 5-year survival was assessed: radiation therapy (40% survival), radiation therapy plus PSK (42%), radiation therapy plus chemotherapy (29%), or radiation therapy plus chemotherapy and PSK (37%).

Glioblastoma

Melatonin

Lissoni 1996 – Melatonin (20 mg daily) was given to 30 patients during radiotherapy, until disease progression. One-year survival was significantly higher in the melatonin plus radiotherapy group (six of 14 patients) than the radiation alone group (one of 16 patients). Quality of life also improved in the melatonin group.

Endometrial

Pyridoxine (vitamin B6)

Ladner 1988 – Patients receiving radiation therapy were randomized to either receive vitamin B6 or not. There was a 15% improvement in the 5-year survival rate in those taking B6.

Bladder

Nicotinamide (a form of vitamin B3)

Hoskin 2010 – Patients receiving radiation for locally advanced bladder carcinoma who also received carbogen (2% CO2 and 98% O2) and nicotinamide had improvement in overall survival, decreased risk of death, and a reduced risk of local relapse compared with those receiving radiation alone.

Eustace 2013 – Patients with bladder cancer received either carbogen and nicotinamide during radiotherapy or radiotherapy alone. Those taking carbogen and nicotinamide with radiation, and showing tumor necrosis, had a 5-year overall survival of 56%. Only 34% of those receiving radiotherapy alone survived five years. Overall survival was not significantly improved in patients who did not have tissue necrosis (tissue death) at baseline.

Head and Neck

Zinc

Lin 2009 – In a double-blind study, patients with advanced (stages III and IV) nasopharyngeal carcinoma were randomized to receive chemoradiotherapy with either 75 mg zinc or placebo daily for two months. The zinc group experienced higher 5-year overall survival and less local recurrence.

Breast

Multivitamins and/or Nutrient Combinations

Lockwood 1994 – In patients undergoing standard treatment for high-risk breast cancer and receiving a combination of antioxidants, quality of life improved and some participants showed partial remission. No deaths occurred in the 24-month study period (statistically deaths were expected among high-risk populations). There was no sign of metastasis in the group receiving antioxidants.

Greenlee 2012 – Decreased risk of breast cancer recurrence was observed in patients taking vitamins C and E during radiotherapy compared with those not taking supplements. Decreased risk of all-cause mortality was observed in vitamin E users.

Kwan 2011 – Patients taking a multivitamin prior to diagnosis and throughout treatment with radiation had reduced recurrence of breast cancer and reduced total mortality.

Multiple Cancers (head and neck, cervical, esophageal, skin, Ewing’s sarcoma)

Ascorbic acid

Hanck 1988 – Patients taking 5 grams ascorbic acid five times daily throughout the entire course of radiotherapy experienced improved response to treatment. Disease-free survival after 6-month follow-up was 67% in the study group and 45% in the control group. The ascorbic acid group also had fewer side effects of radiation therapy.

Brain Metastasis

Omega-3 fatty acids

Gramaglia 1999 – Patients taking supplemental omega-3 fatty acids while being treated with stereotactic radiotherapy had improved survival time and decreased radionecrosis.