Anti Cancer Supplements

INTEGRATIVE MEDICINES

Several cancer survivors have experienced the physical, social, and emotional effects of cancer and its treatments for years in later stages of life. The symptoms exist for a longer duration, including fatigue, pain, neuropathy, lymphedema, difficulty sleeping, weight gain, cognitive dysfunction, sexual dysfunction, and fear of recurrence (Cutshall et al., 2015). Integrative medicines help enhance the individuals’ physical, emotional, and spiritual health by incorporating additional evidence with informed protocols and conventional therapy. Five domain concepts have been introduced that involve manipulative & body-based methods, mind-body medicine, alternative medical systems, energy therapies, and biologically based therapies. The cancer survivors choose integrative medicine to cope-up with long-term adverse effects and symptoms.

Integrative medicine constitutes natural products involving herbs, botanicals, and mind and body practices. The approach of using integrative medicines among cancer patients has involved several medical clinics and cancer centers in fulfilling the demand of the patients by providing integrative medicines. Patients often use the integrative medicines as per their own will, without any discussion regarding their use with their oncologist, which can be dangerous, mainly for oncology patients, who are particularly frail and may require modified holistic treatments. The oncologist further recommends integrative medicine to determine the patient’s cancer journey. Certain herbs and supplements in integrative medicines interfere with chemotherapy drugs, making them less effective. Hence, considering this, the healthcare professional offers patients safe and appropriate care. 

Many cancer patients use integrative medicines that show efficacy in prevention and treatment, boosting the immune system, improving well-being, and reducing the symptoms of either the disease or disease treatment, such as nausea, insomnia, and pain cancer. Its intake, as the healthcare professional recommends, helps improve the quality of life of cancer patients during chemotherapy instead of increasing the therapeutic efficacy. Also, emotional distress, depression, insomnia, nausea, loss of appetite, and other symptoms resulting from disease or treatment are mitigated by adhering to the use of integrative medicines. Integrative medicines include some non-biological medicines such as meditation, deep breathing, or acupuncture that show no risk of drug interactions and are further advisable for cancer patients.

A) Commonly used Integrative medicines:

The integrative medicines provided by Zen Integrative Oncology Wellness Protocol to help the cancer patients are listed below:

1.1 MediZen Medical Cannabis: 

It is produced from the extract of the Sativa plant. It is commonly used for chemotherapy-induced pain control. It shows efficacy in managing nausea and vomiting associated with cancer-associated treatments. MediZen Medical Cannabis extract also acts as an antitumor agent preventing the spread of cancer. It is also helpful in reducing anxiety and enhancing sleep. This natural extract fights cancer, manages pain, induces sleep & improves appetite. It is a highly concentrated, non-diluted extract with CBD: THC ratio of 1:1 and is a concentrated paste in a syringe, allowing easy and precise synthesis. It is approved for manufacturing by FSSAI and AYUSH and trusted by doctors and practitioners worldwide. Its benefits are:

• Chemopreventive protection
• Nausea and vomiting
• Natural pain killer
• Appetite stimulation
• Sleep regulation
• Manages chemotherapy side-effects

1.1.1 Clinical evidences:

Working against cancer growth or preventing its spread improves the chances of survival with the help of treatments and therapies to improve anti-cancer action. As per current research, there is no evidence that medical Cannabis is the cure for cancer. Cannabinoids like CBD and others have exhibited anti-cancer properties. The details are represented below:

• Cannabinoids have reduced breast tumor growth, promoted the death of cancer-producing cells, and reduced the levels of metastasis and angiogenesis (blood vessel growth to supply tumors) in animal studies (Dariš et al., 2019).
• Animal research on rats has shown that Cannabinoids have inhibited growth and led to the death of thyroid cells (Hinz & Ramer, 2019).
• The IL-1 _р secretion and metastasis have drastically reduced in Ovarian Cancer Cells.
• The precursor of CBD, which is CBDA, has inhibited the migration of cancer cells.
• Chemo prevention was observed in Colon Cancer (Zaiachuk et al., 2021).
• An anti-evasive action was observed in the Lung Cancer cells (CBD) (Ramer et al., 2012).

Many results show a positive impact of  medical Cannabis, whereas other studies find a contradiction. For example, in 2013, breast, prostate, glioma, lymphoma, and pancreatic cancer cell studies showed a positive efficacy. Whereas in 2018, studies showed insufficient evidence to prove that medical Cannabis can cure cancer. Thereby, further research is needed for any such conclusions to be drawn to conclude the anti-cancer role of Cannabinoids. 

1.2 AyurZen Ayurvedic Medicine: 

It has been used as an anti-cancer remedy due to its in-built anti-oxidant and anti-inflammatory properties. It is a unique blend of 10 select Herbal Flowers, Roots, Fruits and Seeds, including Catharanthus alba (Flower), Curcuma longa (Root), Ganoderma lucidum (Biomass), Glycine max (Seed), Moringa oleifera (Fruits), Nigella sativa (Seed), Picrorhiza kurroa (Root), Piper cubeba (Seed), Tribulus Terrestris (Fruit), and Withania somnifera (Root). It is a herbal extract to fight cancer, contains anti-oxidant & anti-inflammatory properties, boosts immunity, regenerates cells & reduces side effects of chemotherapy. Its benefits are:

• Anti-inflammation
• Anti-oxidants
• Natural pain killer
• Immunity booster
• Cell repair
• Manages chemotherapy side effects

1.2.1 Clinical evidence of the herbs

• Catharanthus alba: The antioxidant properties of Catharanthus alba are derived using different assay systems such as Hydroxyl radical-scavenging activity, superoxide radical-scavenging activity, DPPH radical scavenging activity and nitric oxide radical inhibition method. The result showed that the ethanolic extract of the roots of Periwinkle varieties has adhered to the good scavenging effect in the complete essay in a concentration-dependent manner (Bhutkar & Bhise, 2011). 
• Curcuma longa: Several studies have been conducted to show clinical characteristics of Curcuma longa through clinical trials showing efficacy in cancer treatment are represented below:

Duration of study	Dosage of the drug	Number of patients	Country	Results	References
11 months	8 g	22	Japan	Increased patient survival	Kanai et al., (2011)
291 days	2 g per day	24	UK	Curcumin was a safe and tolerable adjunct to FOLFOX chemotherapy in patients with metastatic colorectal cancer	Lynne M Howells et al., (2019)

• Ganoderma lucidum: It is commonly known as Reishi, one of the primary herbs of choice in any immune deficiency disease. Randomized control trials have evaluated the effectiveness of G. lucidum medications compared with active or placebo control in cancer patients. A preliminary study using transverse aortic constriction (TAC) was conducted on mice to show anticancer activity and cardioprotective activity (Xie et al., 2016). Its result showed normalized ejection fraction, corrected the fractional shortening generated by TAC, and reduced left ventricular hypertrophy; analysis of total RNA expression revealed the reduced expression of genes associated with cardiac failure and decreasing levels of RNA circ-Foxo3. 
• Glycine max: The soybean seeds are drought-tolerant, nitrogen-fixing plants enriched within the soil. The clinical trial included using human cancer cell lines, which were treated with different concentrations of soybean and transfected with the plasmids (Wang et al., 2018). 
• Moringa oleifera: It consists of antifungal, antiviral, antidepressant, and anti-inflammatory properties. The clinical trial demonstrated the efficacy of anti-cancer activity of Moringa oleifera extracts in human hepatocellular carcinoma HepG2 cells (Jung et al., 2015). Hollow fiber assay is carried out for oral administration of the extract that reduces the proliferation of the HepG2 cells. Hence, this clinical trial depicts the efficacy of Moringa oleifera when administered orally for treating liver and lung cancer.
• Nigella sativa: Some of the clinical trials of Nigella sativa are discussed in below table:

Cancer model	Cancer cells	Intervention	Results	References
In vitro studies	Doxorubicin-resistanthuman breast cancer cells line (MCF-7/DOX cells)	Thymoquinone  (25, 50 or 100 µM) for 48 hours & NSO Nano emulsion	Induces apoptosis, p53 protein showing concentration dependent growth inhibition	Arafa et al., (2011)
In vivo studies	Diethyl nitrosamine induced hepatocarcinogenesis in Wistar rats	Ethanolic extract of NS (250 mg/kg) for 5 consecutive days	Induced  increment of liver weight, hepato-somatic indices, serum AFP and VEGF levels, and hepatic HGFβ protein expression being reversed by the extract.	Shahin et al., (2018)

• Picrorhiza kurroa: The clinical trials are carried out to evaluate the antioxidant and anti-neoplastic activities of methanolic and aqueous extracts of roots of Picrorhiza kurroa (Rajkumar et al., 2011). Different types of cancer cell lines are used to evaluate the cytotoxicity of the extracts tested by XTT assay. The results revealed the efficacy of  Picrorhiza kurroa in showing antioxidant properties. The dosage has been effective in targeting cells towards apoptosis. It is influential in the development of drugs for cancer.
• Piper cubeba: Cubebin is the vital constituent isolated from the seeds of Piper cubeba. Its different types of derivatives are tested for evaluating the in vitro anticancer activity against various types of human cancer cell lines using MTT assay (Rajalekshmi et al., 2016). The result of this test showed anticancer effects. The derivatives acted through the apoptosis-mediated cell death pathway, which would effectively develop novel anticancer agents.
• Tribulus terrestris:   It effectively enhances athletic performance and bodybuilding and treats heart and circulatory conditions and sexual issues. When the clinical trial was carried out in mice, the treatment of TT showed protection against radiation damage by inhibiting radiation-induced glutathione depletion and decreasing lipid peroxidation levels in the liver of mice (Kumar et al., 2009).
• Withania somnifera: In vitro cytotoxic evaluation of 50% ethanolic extract of root, stem, and leaves against different human cancer cell lines, e.g., prostate, lungs, colon, and neuroblastoma, showed more effective antitumor activity against Prostate and Colon Cancer than roots and stem extracts (Yadav et al., 2010). Another clinical trial showed anti-carcinogenic activity against urethane-induced lung cancer in adult male albino mice (Achar et al., 2018). 

1.3 MediZen Grape Seed Extract: 

It is a natural antioxidant. It eliminates free radicals, which are responsible for cancer creation. It is thus helpful in treating cancer, diabetes and heart diseases. It also protects from bacterial infections and helps heal wounds. It is combined with proanthocyanidins for better drug interaction and is available as capsules for easy consumption.  Its benefits are:

• Reduces inflammation
• Immunity booster
• Cell repair
• Improves Vitamin C & E levels
• Maintains blood pressure
• Manages heart diseases 

1.3.1 Clinical evidences:

Different preclinical studies have been carried out using in vitro approaches and in vivo analyses in animal models that show the protective effects of grape seed extract and its active constituents grape seed proanthocyanidins against skin and breast, prostate, head and neck and lung cancer. The grape seed constituents possess antioxidant and anti-inflammatory properties. Different clinical studies have represented multiple molecular targets affected by treatment with grapeseed extract. Some of them are described below:

• Dietary feeding of proanthocyanidins extracted from grape seeds protects skin from the adverse biological effects of solar ultraviolet (UV) radiation and prevents skin cancer (Mittal et al., 2003).
• Grape seed proanthocyanidins induce apoptosis and inhibit metastasis of highly metastatic breast carcinoma cells (Mantena et al., 2006).
• The grape seed extract provides efficacy in the chemoprevention of prostate cancer to control this malignancy (Raina et al., 2007).
• 50% survival rate of head and neck squamous cell carcinoma (HNSCC) has represented an improvement due to the chemotherapeutic effect of proanthocyanidins on HNSCC cells (Prasad et al., 2012).
• Grape seed extract efficacy is observed during chemotherapy in non-small cell lung cancer that results in proliferation, apoptosis, and expression of receptors.

1.4 MediZen Reishi Mushroom: 

It is a natural remedy for chronic stress and fatigue. It is universally used for cancer treatment, side effect management of chemotherapy and radiation, Alzheimer’s, diabetes and cold sores. It is a natural dietary product to boost immunity, reduce stress & fatigue. Its benefits are:

• Chemopreventive protection
• Improve sleeping schedule
• Anti-viral
• Anti-fatigue
• Anti-anxiety and depression
• Natural pain killer

1.4.1 Clinical evidence

Reishi Mushroom is obtained from traditional Chinese medicine, and Ganoderma Lucidum is a species of reishi mushroom. It effectively extends an individual’s life and promotes health benefits. It shows efficacy in preventing and treating many diseases and exerts anti-cancer properties. It benefits cancer patients and is most often used in drug development after testing its reliability. It is usually recommended as an immune system support supplement in cancer treatment. The clinical evidence and preclinical trials of the reishi mushroom have shown promising results of its antitumor activity. It can stimulate host immune functions by increasing CD3, CD4 and CD8 lymphocyte percentages. Some of the clinical evidence are discussed below:

• Administration of Reishi mushrooms in lung cancer patients has shown improved tumor response (Liu et al., 2020).
• When taken in the form of drugs, the Reishi mushroom helps reduce cell viability in human colon cancer cells (Liang et al., 2014).
• It inhibits prostate cancer-dependent angiogenesis and has been considered a potential therapeutic use for the treatment of prostate cancer (Stanley et al., 2005).
• It inhibits the invasion of breast and prostate cancer cells by a common mechanism and could have potential therapeutic use for cancer treatment (Sliva et al., 2002).
• The effects of Reishi on viability, apoptosis, invasion, and its mechanism of action in the cancer cells of inflammatory breast cancer (Martínez-Montemayor et al., 2011).

1.5 MediZen Curcumin: 

It is a natural compound found in the turmeric plant. It has been proven to reduce inflammation, increase antioxidants, reduce pain & regenerate cells. It also helps in blood circulation and improves immunity. Its benefits are:

• Anti-Inflammation
• Anti-Oxidants
• Immunity booster
• Natural pain killer
• Anti-anxiety and depression
• Metabolism regulation
• Reduces LDL-cholesterol level, glucose and blood pressure

1.5.1 Clinical evidence

Curcumin is known to have antioxidant, anti-inflammatory, and anti-cancer effects. These effects have played an essential role in preventing and treating various illnesses ranging from cancer to autoimmune, neurological, cardiovascular diseases, and diabetes. Furthermore, it is aimed to increase the biological activity and physiological effects of curcumin on the body by synthesizing curcumin analogues. Curcumin is considered an essential therapeutic agent and is currently being tested for the human trials to determine different conditions such as myeloma, pancreatic cancer, colon cancer, mastitis myelodysplastic syndromes, psoriasis, Alzheimer’s disease, diabetic nephropathy, periodontal disease, oral cancers, recurrent aphthous stomatitis, precancerous lesion and conditions etc. Preliminary findings from many small and uncontrolled studies indicate that curcumin is effective in treating cancer.

• Colorectal Cancer: The clinical results of curcumin administration in patients with colorectal cancer results in sufficient curcumin concentrations that persist in colonic mucosa. Higher curcumin exposure achieved by several newer formulations has shown important implications for the optimal treatment of cancers other than those in the gastrointestinal tract (Adiwidjaja et al., 2017).
• Pancreatic Cancer: Higher survival rates have been observed among patients with gemcitabine-resistant pancreatic cancer compared to gemcitabine alone (Kanai et al., 2011). Oral curcumin is well tolerated and, despite its limited absorption, shows biological activity in patients with pancreatic cancer (Dhillon et al., 2008).
• Anti-cancer effects of curcumin are reported against several different types of cancer, including prostate cancer, breast cancer, colorectal cancer, pancreatic cancer, and head and neck cancer, both in vitro and in vivo. 
• Multiple myeloma: The clinical trial of curcumin shows the potential to slow the disease process in patients suffering from multiple myeloma (Golombick et al., 2012).

1.6 MediZen Green Tea Extract: 

• It has been proven to have anti-free radicals and antioxidant properties. It works on enhancing the immune system function and boosting metabolism. lt has been known to display free radical scavenging activity and protect cells from DNA damage. It also helps reduce cholesterol and makes the heart healthy. Its benefits are:

• Manages heart diseases
• Manages liver disease
• Boosts immunity
• Reduces cholesterol
• Controls blood pressure 
• Regulates metabolism 

1.6.1 Clinical evidence

Several preclinical studies of green tea and its components have been reported to represent efficacy for the growth inhibition of tumors with fewer adverse events. Several clinical studies regarding the green tea extract show efficacy in cancer treatment, mainly involving breast cancer, colorectal cancer, prostate cancer, ovarian cancer, liver cancer, lung cancer, lymphoma, gastric cancer, and pancreatic cancer. Some of them are discussed below:

• Supplementation with Brazil nuts and green tea extract has shown efficacy in regulating targeted biomarkers concerning colorectal cancer risk in humans (Hu et al., 2016).
• The randomized, placebo-controlled, double-blinded trial investigated the efficacy of green tea extract as a biomarker by evaluating its daily consumption for 12 months in patients with breast cancers (Samavat et al., 2015).
• Daily intake of a standardized, decaffeinated catechin mixture accumulates in the plasma, and its dose is well tolerated among the patients showing a reduction in the likelihood of prostate cancer in men (Kumar et al., 2015).
• Green tea consumption has shown efficacy in chemoprevention among individuals with a high risk of liver cancer (Luo et al., 2006).

1.7 MediZen Milk Thistle: 

It is a natural nutraceutical to boost the immune system, increase antioxidants, protect the liver, and regenerate cells. Its flowering herb has proven anti-cancer properties. It helps the body get rid of toxins and promotes healthy cell repair. Its benefits are:

• Antioxidants
• Cell repair
• Improves brain function
• Promotes digestive health
• Manages weight loss
• Detoxification

1.7.1 Clinical evidence:

Its application has been studied by conducting both in vivo and in vitro studies, mainly showing efficacy in cancer. It is considered a chemopreventive agent against various cancer types. Its anti-cancer effects are implicated by the modulation of specific proteins that show anti-inflammatory and anti-metastatic activities. The possible anti-cancer mechanism of Silymarin includes anti-inflammation, cell regulation, apoptosis induction, inhibition of angiogenesis, inhibition of invasion and metastasis, and growth inhibition. Some of the clinical evidence of Silymarin milk thistle has been discussed below:

• Hepatoprotective effects of milk thistle are observed among the patients undergoing chemotherapy which is most often toxic to the liver (Siegel & Stebbing, 2013).
• The children undergoing chemotherapy for acute leukemia recommended that milk thistle is effective in improving liver function in children. However, there was a trend toward greater chemotherapy doses in those who received milk thistle (Ladas et al., 2010).
• Other studies have also revealed that the patients undergoing chemotherapy have shown an increased concentration of liver enzymes during treatment for leukaemias which was improved by administering milk thistle (Ramasamy & Agarwal, 2008).
• The milk thistle compounds have shown anti-cancer effects in preclinical models, mainly involving induction of apoptosis in the case of colon cancer cells that causes senescence of cancer cells in a mouse model of breast cancer and shows blocking of angiogenesis in prostate cancer models (Deep & Agarwal, 2010). 
• The compounds of milk thistle have shown prevention from the development of skin cancers when carried out on the skin of mice exposed to ultraviolet radiation (Prasad et al., 2020).

1.8 Melatonin: 

It is the hormone produced by the pineal gland within the brain. It helps in regulating sleep and wake cycles. Melatonin is found in fruits, nuts, olive oil and wine. It is also available as a supplement used as a sleep aid. The cancer is aggressive among patients who have nighttime production of melatonin. The supplementation of melatonin in cancer patients shows anti-cancer effects. Melatonin is used as an adjuvant to establish improved outcomes and responses to conventional treatments in cancer. It has improved the quality of life among cancer patients by reducing side effects and symptoms. The measurement of melatonin concentration in blood and urine is associated with cancer risk. Reduced risk of cancers has been observed with melatonin supplementation (Li et al., 2017).

1.8.1 Clinical evidence

The clinical evidence for melatonin is illustrated below:

• Studies have revealed that administration of melatonin in combination with tamoxifen in women with breast cancer showed progression (González-González et al., 2018). The simultaneous administration of melatonin and tamoxifen evolved cancer regression in women with metastatic breast cancer that did not respond to tamoxifen alone. 
• The parallel administration of melatonin with interleukin 2 in patients suffering from distant metastases of non-small cell lung carcinoma, liver carcinoma, bowel carcinoma, stomach carcinoma, pancreatic carcinoma and breast cancer results in cancer regression and disease stabilization (Gurunathan et al., 2021). 
• Melatonin inhibits the growth of breast cancer cells, cervical cancer cells and ovarian cancer cells. It is a group of regulatory factors that controls cell multiplication and death (Shen et al., 2016).
• When used with chemotherapy and radiotherapy, increased survival rates have been observed in people with skin cancer (Pourhanifeh et al., 2019).

1.9 Vitamin D3:

Vitamin D is a fat-soluble vitamin produced by the body when the skin is exposed to ultraviolet rays in sunlight. It is found naturally in some food items such as egg yolks, cod liver oil, fish oil, wild fish such as salmon, sardines, herring and cod, blood sausage, organ meats such as liver, butter, and mushrooms that have been exposed to sunlight. Also, vitamin D is found in some dairy products, orange juice, soy milk and cereals and is primarily available as a dietary supplement. Vitamin D intake works against cancer growth or spread, improving survival, or working with other treatments or therapies to enhance their anti-cancer action. 

1.9.1 Clinical evidence

Some of the clinical evidence are discussed below:

• The high vitamin D serum levels have decreased the death rate among breast cancer patients (Maalmi et al., 2014).
• Better prognosis with medium or high vitamin D serum levels is evaluated compared with low levels, with a more substantial effect in patients receiving hormone therapy (Tretli et al., 2009).
• Supplementation of vitamin D shows cell-killing (cytotoxic) effects of docetaxel which is used in treating breast, lung, prostate, stomach, and head and neck cancers (Frenkel & Gupta, 2010).
• Regression and improved metabolic status is observed in cervical intraepithelial neoplasia grade 1 (Vahedpoor et al., 2017). 
• Reduction in the progression of low-grade prostate cancer in pilot studies has been evaluated (Ahn et al., 2016).

1.10 Essential Oils:

Essential oils are complex mixtures of low molecular weight compounds extracted from plants. The main constituents of essential oils include terpenes and phenylpropanoids, which possess biological and pharmaceutical properties showing insecticidal, parasiticidal, antimicrobial, antioxidant, anti-inflammatory, analgesic, antinociceptive, anticarcinogenic, and antitumor properties. Essential oils are obtained from aromatic plants’ secondary metabolites possessing different functions. It acts as a defense against herbivores, insects, and microorganisms, maintains communication with plants of the same species and helps to signal within the plant in response to environmental stimuli. These have been effective in treating diseases involving emetics and laxatives, muscle relaxants, cardiac stimulants, and cardiac depressants resulting in hypotension and induction of bradycardia. 

1.10.1 Clinical Evidence:

Essential oils have been used as dietary supplements. It acts as an anti-cancer therapeutic agent that helps cancer prevention while establishing tumor cells and interacting with the microenvironment. Some of the clinical evidence of essential oils are discussed below:

• The essential oils are used as complementary and alternative medicine among patients with colorectal cancer (Tough et al., 2002).
• It shows anti-proliferative effects on human metastatic breast cancer cell lines (Arunasree, 2010). 
• The constituents of essential oils induce cell cycle arrest and mitochondria-mediated apoptosis in human cervical cancer (HeLa) cells (Priyadarsini et al., 2010).

1.11 Astragalus

Astragalus is one of the most common herbs derived from traditional Chinese medicine and is effective in treating different cancer types such as breast, colorectal, esophageal, lung and stomach cancers. It effectively reduces the side effects of cancer treatment and helps improve quality of life. It possesses anti-inflammatory and enhances immune function. It is often used in combination with other traditional Chinese medicine herbs.

1.11.1 Clinical evidence:

Different clinical studies have represented an improved survival rate with the treatment using Astragalus. Some of them are described below:

• The use of Astragalus radix shows efficacy in improving the tumor response to chemotherapy (Zhu et al., 2016).
• Astragalus membranaceus has shown efficacy in increasing the chemotherapy completion rate in breast cancer with the chemotherapy-associated hand-foot syndrome (Yu et al., 2020).
• The use of Astragali radix with other herbal medicines has improved the clinical effectiveness and survival rate in patients with advanced colorectal cancer who are undergoing chemotherapy (Huang et al., 2019).
• The use of astragalus polysaccharide injections in radiotherapy among oesophagal cancer patients has shown an improved overall response rate (Zhongguo et al., 2015).
• Astragalus-based botanical therapy is integrated for patients with small-cell lung cancer, showing increased effectiveness of platinum-based chemotherapy with improved survival, performance status and tumor response rate (Wang et al., 2016).
• Improved clinical efficacy and overall response are observed with astragalus polysaccharides injection when used with the FOLFOX regimen in case of stomach cancer (Zhang et al., 2017).

1.12 European Mistletoe

Mistletoe is a woody plant material belonging to different species. European mistletoe (Viscum album) is the raw mistletoe plant. Its raw plant material and berries are toxic, but its pure extracts have benefits when injected or infused. It consists of various biologically active compounds, among which lectin is the most important. It shows toxicity to cancer cells and effectively stimulates the immune system, showing anti-cancer activities. Mistletoe preparations are used by administering subcutaneous, intramuscular, intrapleural injections or as an intravenous infusion. High-dose of European mistletoe has interrupted the recurrent tumors among the cancer patients with recurrent cancer (von Schoen-Angerer et al., 2015). It supports the immune system by increasing the number and activities of white blood cells, mainly the natural killer (NK) cells.

1.12.1 Clinical evidence:

Different clinical studies have represented an improved survival rate using European Mistletoe treatment. Some of them are described below:

• European Mistletoe effectively improves survival and prolonged relapse intervals in breast cancer (Ziegler et al., 2010).
• Fewer lung metastases and a lower adjusted hazard ratio for brain metastases, along with significantly longer tumor-related survival, overall survival, disease-free survival and brain metastases-free survival of primary intermediate- to high-risk malignant melanoma patients without distant metastases following surgery are observed (Augustin et al., 2005).
• Effectiveness in improving the overall survival rate in ovarian cancer patients has been observed in the case of distant metastasis using mistletoe extracts (Grossarth-Maticek & Ziegler, 2007).
• The patients of pancreatic cancer who have undergone improved adjuvant chemotherapy with gemcitabine after surgery are recommended for using mistletoe showing improved survival rate (Matthes et al., 2010). 

1.13 Turkey Tail Mushroom: 

It is a traditional Chinese medicine with the formulation of PSK or Krestin™ being majorly used in Japan. It enhances immune-modulating effects and is considered an adjuvant or supplement in cancer treatment. The major constituents of turkey tail mushrooms are related to their medicinal properties involving β-glucans, PSK (protein-bound polysaccharide, β (1-4)D-glucan protein): Krestin (Japanese formulation), PPSP (polysaccharopeptide), and Ergosterol (provitamin D2 derivatives). It shows efficacy in combination with evidence-based conventional treatment, such as chemo/radiotherapy or surgery. PSK (a glycoprotein-bound mixture) is the best-known component of the turkey tail showing an anti-cancer mechanism. 

1.13.1 Clinical evidence:

Different clinical studies have shown improved survival rates with the treatment using turkey tail mushrooms. Some of them are described below:

• The prolonged survival rate in patients with breast cancer has been observed who have used turkey tail mushroom (Eliza et al., 2012).
• It has shown efficacy in improving the five-year disease-free rate and survival after curative gastrectomy for gastrointestinal cancer patients (Nakazato et al., 1994).
• Improved overall survival is observed when used as an adjunct with chemo/radiotherapy or surgery in a trial with nasopharyngeal cancer (Zhong et al., 2019).

B) Other cancer types evidence:

Breast cancer: Some of the integrative medicine for breast cancer are illustrated below:

• Cancer treatment: Grape seed extract, Flaxseed lignans, Mistletoe extract, Melatonin (with caution during surgery), Reishi mushroom, Vitamin D, Curcumin, Silymarin, Medical cannabis and cannabinoids, Turkey tail mushroom
• Management of side-effects and promoting wellness: Ginger, Medical cannabis and cannabinoids, Grape seed extract, Vitamin D, Curcumin, Melatonin, Astragalus, Bromelain, Coenzyme (CoQ10), Guarana, Mistletoe extract  
• Optimizing body function: Curcumin, Reishi mushrooms, Astragalus, Omega‐3 fatty acids, Ginseng, Medicinal mushrooms such as agaricales, maitake, reishi and shiitake

Colorectal cancer: The integrative medicines effective for colorectal cancer care are illustrated below:

• Cancer treatment: Grape seed extract, Reishi mushroom, Vitamin D, Curcumin, Medical cannabis and cannabinoids, Medicinal mushrooms such as turkey tail mushrooms or extracts, shiitake mushroom extracts
• Management of side-effects and promoting wellness: Ginger, Medical cannabis and cannabinoids, Grape seed extract, Vitamin D, Curcumin, Melatonin, Omega‐3 fatty acids, Beta-glucans, Milk thistle, Astragalus, L‐glutamine (glutamine), Probiotics
• Risk reduction: Curcumin, Medical cannabis, Melatonin, Beta-glucan, Calcium supplements, Magnesium supplements, Vitamin B2 supplements, Medicinal mushrooms such as  reishi mushrooms, turkey tail mushrooms or extracts
• Optimizing body function: Curcumin, Reishi mushrooms, Omega‐3 fatty acids, Beta-glucans, Grape seed extract, Green tea extract, Aged garlic extract, Astragalus and other saponins, EGCG supplements, L‐glutamine, Probiotics, Vitamin E supplements 

Ovarian cancer:  Following are the natural products effective for ovarian cancer care:

• Cancer treatment: Combination therapy of Indole 3‐carbinol (I3C) and EGCG, Grape seed extract, Melatonin (with caution during surgery), Reishi mushroom, Vitamin D, Curcumin, Silymarin, Medical cannabis and cannabinoids
• Management of side-effects and promoting wellness: Ginger, Medical cannabis and cannabinoids, Curcumin, Melatonin, Panax ginseng, Vitamin E
• Optimizing body function: Isoflavones including genistein from Soy, Selenium, Milk thistle, Silymarin

Prostate cancer: Following are the natural products effective for prostate cancer care:

• Management of side-effects and promoting wellness: Cranberry juice or extract, Medical cannabis and cannabinoids, Grape seed extract, Curcumin, Melatonin
• Risk reduction: Grape seed extract, Lycopene, Quercetin

Kidney cancer: Following are the natural products used as integrative medicine for patients with kidney cancer:

• Cancer treatment: Integrative medicines used in kidney cancer treatment includes:
• Grape seed extract: It shows antioxidative activity and anti-inflammatory effects that improves renal injury in case of surgery in kidney cancer. 
• Melatonin: It induces apoptosis in renal cancer cells through up-regulating the expression of E2F1 and Sp1, leading to the enhancement of the expression of Bcl-2-interacting mediator of cell death. 
• Curcumin: It promotes cell cycle arrest and inhibits survival of human renal cancer cells by negative modulation of the PI3K/AKT signaling pathway. 
• Amygdalin: It reduces the growth of renal cancer cells and proliferation. 
• Thymoquinone: It induces autophagy in renal cell cancer cells.  
• Englerin: It kills kidney cancer cells. 
• Vitamin E: It reduces renal cortex superoxide production and preserves nNOS abundance that helps in restoring local balance between NO and superoxide in the kidney.
• Genistein: It induces cell apoptosis and inhibits the proliferation of kidney cancer cells via regulating CDKN2a methylation. 
• Coumarin: It shows efficacy in  counteracting the side effects caused by radiotherapy in renal cell carcinoma. 
• Sulforaphane: It inhibits proliferation and invasive activity of everolimus-resistant kidney cancer cells.
• Honokiol: It shows efficacy in inhibiting the growth of renal cancer cells  by releasing in the form of therapeutic agents-loaded electrospun scaffolds in the treatment of kidney cancer.
• Kahweol: It inhibits the renal cancer proliferation and migration by inducing apoptosis in kidney cancer.
• Alpinumisoflavone: It shows anti-tumor effects in the treatment of renal cell carcinoma.

Management of side-effects and promoting wellness: Following integrative medicines are used for reducing the side-effects and enhances the health outcome of the kidney cancer patients:

• Reishi mushroom: It makes the kidney less spongy, helps with proteinuria and helps stop the erosion of the outer membrane of the nephron by reducing kidney inflammation. 
• Medical cannabis and cannabinoids:  It provides relief from pain and other symptoms of kidney cancer during and after chemotherapy.
• Curcumin: It reduces inflammation in patients with kidney cancer. 
• Quercetin:  It protects the kidney by lowering glucose, reducing oxidative stress while increasing the antioxidant capacity of cells, and delaying fibrosis by inhibiting the conversion of renal tubular epithelial cells in kidney cancer.
• Grape seed extract: It reduces kidney damage and improves function by reducing oxidative stress and inflammatory damage.  
• Silymarin: It helps in reducing the side-effects and toxicity of chemotherapeutic drugs in renal cancer. 
• Milk thistle: It supports detoxification while enhancing kidney functions.

Optimizing body function: Following integrative medicines are used for optimizing body functions in  kidney cancer patients:

• EGCG supplements: It improves the renal function and attenuates renal fibrosis, which indicates that it may lower blood pressure via exerting renal protective effects.

Brain cancer: Following are the natural products used as integrative medicine for patients with brain cancer:

• Cancer treatment:  Integrative medicines used in brain cancer treatment includes:
• Reishi mushroom: It stimulates nerve growth promoting communication among the neurons in the brain and helps in protecting the brain against seizures.
• Curcumin: It is used as a therapeutic agent in case of brain tumors including glioblastoma multiforme.
• Procyanidin: It is the inhibitor of P-glycoprotein in the blood brain barrier and shows chemo-sensitizing effects in human cerebrum in brain cancer. 
• Scillarenin: It improves the efficacy of therapy regimens in treating brain cancer.
• Latex: It causes cell death in case of brain cancer while showing synergistic response among patients. 
• Ethanolic extract of Propolis: It inhibits proliferation in glioblastoma and fibroblast cell lines. 
• Propolisis: It increases the sensitivity of human brain cancer cells when combined with TMZ, showing efficacy  glioma therapy. 
• Tetrandrine: It inhibits cell migration and invasion in human brain glioblastoma multiforme GBM 8401 cells.
• Quercetin: It inhibits the tumor cell proliferation in case of glioblastoma, 

Management of side-effects and promoting wellness: Following integrative medicines are used for reducing the side-effects and enhances the health outcome of the brain cancer patients:

• Grape seed extract: It is used as a dietary supplement and possesses water-soluble properties that are capable of crossing the blood-brain barrier more easily than other natural antioxidants. 
• Melatonin: It reduces the side effects associated with chemotherapy and radiation therapy by exerting synergistic effects in brain cancer.
• Silymarin: It is effective in reducing brain metastasis by eliminating metastasis by traversing the blood–brain barrier.
• Medical cannabis and cannabinoids:  It provides relief from pain and other symptoms of brain cancer during and after chemotherapy.
• Ginger: It possesses anti-inflammatory properties that increase serotonin and dopamine levels and reduces  inflammation in the brain.
• Ginseng: It is effective in memory improvement and the direct prevention of brain cancer.
• Vitamin E supplements: It helps in prolonged survival in patients with malignant glioma.
• Probiotics: It is used as  replacement or a complementary therapy in case of glioblastoma cancer. 
• Omega-3 fatty acids: It is effective in brain development  and reduces the risk of brain cancer development.
• Essential oils: It is effective in improving cognitive function and improves brain function in case of surgery or brain injury in brain cancer patients. 

Optimizing body function:  Following integrative medicines are used for optimizing body functions in  brain cancer patients:

• EGCG supplements: It protects the brain from oxidative stress and reduces brain damage.

Pancreatic cancer:  Following are the natural products used as integrative medicine for patients with pancreatic cancer:

• Cancer treatment:  Integrative medicines used in pancreatic cancer treatment includes:
• Melatonin: It shows the therapeutic approach of antioxidants and tissue protector against inflammation and oxidative stress in pancreatic cancer.
• Reishi mushroom: It shows anti-cancer potential when used in pancreatic cancer when the patient undergoes specific chemotherapy.
• Curcumin: It suppresses tumor growth in pancreatic cancer cell lines in a time and dose-dependent manner by inhibiting nuclear transcription factor-kappa B (NF-κB). 
• Polydatin (Polidal-Ghimas): It possesses antimutagenic and antitumor action, involving pathways related to cell cycle, apoptosis, angiogenesis, and metastatic progression in pancreatic cancer. 
• Kampo: It is used as medicine in advanced pancreatic cancer cases for prolonged survival. 
• Shiitake extract: It is used as oral formulation showing extended survival rate among patients of pancreatic cancer. 
• Lactoferrin: Its oral administration controls the tumor proliferation, survival, migration, invasion, and metastasization in patients of pancreatic cancer. 
• Active Hexose Correlated Compound (AHCC): It shows efficacy in downregulating the HSP27 of pancreatic cancer cells and helps in the cytotoxic effect of gemcitabine. 
• Artemisinin: It shows growth inhibitory effects on pancreatic cancer cells as a single agent or in combination with gemcitabine. 

Management of side-effects and promoting wellness: Following integrative medicines are used for reducing the side-effects and enhances the health outcome of the pancreatic cancer patients:

• Mistletoe: It improves the quality of life among patients suffering from locally advanced or metastatic pancreatic carcinoma. 
• Silymarin: It inhibits pancreatic cancer growth and reduces pancreatic cancer induced cachexia or weakness. 
• Medical cannabis and cannabinoids:  It provides relief from pain and other symptoms of pancreatic cancer during and after chemotherapy.
• Curcumin: It is effective in reducing the inflammation of the pancreas.   
• Milk thistle: It protects the pancreas from causing any side effects during the chemotherapy sessions for pancreatic cancer. 
• Vitamin D:  It acts as a protective factor in reducing the risk of pancreatic cancer by regulating the cell cycle differentiation.
• Vitamin E supplements: It acts as antioxidants and reduces the incidence of pancreatic cancer by inhibiting the pancreatic cancer cell line growth. 

Selenium: Its intake reduces the risk of pancreatic cancer development, lessens pain, and prevents pancreatitis recurrences.

• Probiotics: Probiotics: It suppresses the growth of pancreatic cancer cells by showing antiproliferative properties and regulating intestinal immunity.
• Optimizing body function: Following integrative medicines are used for optimizing body functions in pancreatic cancer patients:
• Green tea extract: It inhibits growth and induces apoptosis in human pancreatic cancer cells and suppresses the process of pancreatic carcinogenesis.  
• Probiotics: It releases cytokines that act against pathogens in case of pancreatic cancer and helps in boosting the immune response.

Liver cancer: The integrative medicines effective for the treatment of liver cancer are illustrated below::

• Berberine: It is capable of suppressing the proliferation of liver cancer cells showing a clinical approach in the form of anti-tumor drug.
• Flavonoids: It shows reaction while arresting the cell cycle, inducing apoptosis and suppressing the cancer cell proliferation.
• Brucein D:  It shows anti-cancer activity in the case of hepatocellular carcinoma.
• Matrine: It shows efficacy in cancer cell proliferation  by strengthening  anti-cancer capacity of chemotherapeutic drugs.
• Longikaurin A: It induces arresting of cell cycle and apoptosis in  the case of hepatocellular carcinoma.
• Isoquercitrin:  It is capable of inhibiting the progression of liver cancer through the molecular mechanism of the MAPK signaling pathway.
• Gigantol: It shows inhibition of proliferation and induction of apoptosis by liver cancer HepG2 cells.  
• Curcumin: It shows efficacy as an anti-cancer agent in treating liver cancer and decreases the chances of recurrence.

Management of side-effects and promoting wellness: Following integrative medicines are used to reduce the side effects and enhance the health outcome of liver cancer patients:

• Astragalus: It possesses antibacterial and anti-inflammatory properties that protect the liver from infection and inhibit tumor growth by inducing apoptosis.
• Reishi mushroom: It reduces the chances of hepatitis B infection in liver cells and improves the function of the liver. 
• Planch root extract: It inhibits cancerous biological behavior of hepatocellular carcinoma cells by regulating epithelial-mesenchymal transition.
• Ganoderma lucidum polysaccharide (GLP): It enhances radiosensitivity while showing therapeutic effect on hepatocellular carcinoma cells. 
• Grape seed extract: It shows efficacy in improving the grade of fatty liver changes showing anti-cancer effects. 
• Selenium: It suppresses liver cancer carcinogenesis and improves the liver function by reducing the serum aspartate transaminase and alanine transaminase.
• Medical cannabis and cannabinoids:  It relieves  pain and other symptoms of liver cancer during and after chemotherapy.
• Curcumin: It helps in reducing inflammation in the case of liver cancer. 
• Probiotics:  It influences the gut microbiota and modulates pathogenesis in liver cancer.
• Aloe vera: It acts as an  antioxidant by cutting down the free radicals from the body and boosting the immune response.
• Reishi mushroom: It stimulates the compounds that are responsible for tumor suppression and decreases inflammatory compounds in the liver.
• Fucoidan: It shows anti-metastatic effects showing biological mechanisms in human liver cancer cells. 
• Lactone: It shows efficacy in lowering portal hypertension by improving liver fibrosis in liver cancer.
• Vitamin C: It shows antioxidant effects, helps defend against liver damage, and prevents cirrhosis.
• Garlic: It cleanses the liver and triggers the liver enzymes by flushing out the toxins naturally. 
• Ginger: It inhibits liver carcinogenesis through the downregulation of elevated NF-κB and TNF-α. 
• Silymarin: It acts as a free radical scavenger and modulates the enzymes concerned with the liver.

Optimizing body function: Following integrative medicines are used for optimizing body functions in liver cancer patients:

• Green tea extract: It regulates lipid metabolism, reducing lipids accumulation in the liver.
•  EGCG supplements:  It inhibits the growth and induces apoptosis of different liver cancer cells by activating other molecular mechanisms.
• Milk thistle: It helps treat liver inflammation in cancer patients who receive chemotherapy.

Head & neck cancer: The integrative medicines effective for head & neck cancer are illustrated below:

• Cancer treatment: Integrative medicines used in head and neck cancer treatment includes:
• Mistletoe extract: It promotes tumor defense by eliminating minimal residual cancer cells in patients with head and neck cancer.
• Gossypol: It inhibits growth and promotes apoptosis of human head and neck squamous cell carcinoma.
• Curcumin: It inhibits proliferation, migration, invasion and metastasis and induces apoptosis via modulating multiple signaling pathways in head and neck cancer. 
• Vitamin A: It shows strong differentiation induction effects with anti-tumor effect on head and neck squamous cell carcinoma. 
• Black raspberry extracts: It induces apoptosis and terminal differentiation and suppresses the translation of VEGF (vascular endothelial growth factor).
• Bowman Birk inhibitor (BBI): It acts as a chemopreventive agent in treating head and neck cancer.
• Cucurbitacins: It is a highly potent inhibitor of cell proliferation and viability. It inhibits the proliferation of both SCC-40 cells and UM-SCC-47.

Management of side effects and promoting wellness: Following integrative medicines are used to reduce the side effects and enhance the health outcome of head and neck cancer patients:

• Green tea extract: It protects against various steps in cancer progression and invasion through multiple and complex signal transduction pathways.
• Reishi mushroom: It exerts anti-cancer properties and improves survival rates among head and neck cancer patients.
• Selenium: It results in a cell-mediated immune response when taken during therapy.  
• Medical cannabis and Cannabinoids: It relieves pain and other symptoms of head and neck cancer during and after chemotherapy.
• Vitamin A: It shows anti-tumor effect on head and neck squamous cell carcinoma patients. 
• Curcumin: It suppresses the growth of xenograft derived from head and neck cancer. 
• L‐glutamine (glutamine): It maintains the patients’ nutritional status and reduces the patients’ diet-related or other side effects caused by radiotherapy. 
• Probiotics: It is effective in reducing oral Candida spp, which can be recommended alone or in combination with traditional antifungal agents for effective reduction of oral Candida in the head- and neck-radiotherapy patients.  
• Aloe vera:  It reduces the severity of radiation-induced mucositis without side effects.
• Sandalwood oil:  It prevents radiodermatitis in head and neck cancer patients undergoing radiation therapy.
• Indigowoad root extract: It enhances immune response while the patients with head and neck cancer undergo radiation therapy. 

Optimizing body function: Following integrative medicines are used for optimizing body functions in head and neck cancer patients:

• Green tea extract: It protects against diverse steps in cancer progression and invasion through multiple and complex signal transduction pathways in patients with head and neck cancer.
• EGCG supplements: It protects against various steps in cancer progression and invasion through multiple and complex signal transduction pathways in head and neck cancer patients.
• Milk thistle: It prevents radiotherapy-induced mucositis in patients with head and neck cancer.

Blood cancer:  Following are the natural products used as integrative medicine showing efficacy among leukemia patients:

• Cancer treatment:  Integrative medicines used in blood cancer (leukemia) treatment includes:
• Vitamin C:  It suppresses the development of leukemia from blood- forming stem cells. 
• Curcumin: It helps to stabilize the condition of chronic lymphocytic leukemia.
• Reishi mushroom: It has potency, and the ability to selectively target leukemia cells makes it a promising candidate for cancer treatment.
• Melatonin: It suppresses the growth of the human myeloid leukemia HL‐60 cells by blocking the progression from G1 to the S phase. 
• Vitamin E:  It reduces tumor growth rate, improves host survival and increases serum vitamin E level.
• Omega‐3 fatty acids: It can selectively kill the leukemia-causing stem cells. 
• Probiotics: It induces tumor cell apoptosis and inhibits tumor cell proliferation and metastasis. 
• Aspirin: It induces apoptosis of chronic lymphocytic leukemia (CLL) cells.

Following integrative medicines are used to reduce the side effects and enhance the health outcome of blood cancer (leukemia) patients:

• Grape seed extract: It has the potential to curb leukemia.
• Medical cannabis and cannabinoids: It relieves pain and other symptoms of blood cancer during and after chemotherapy.
• Garlic: It inhibits proliferation and induces apoptosis of human leukemia cells and induces apoptosis in myeloblasts. 
• Ginseng: It induces the inhibition of proliferation and differentiation of leukemia.  
• Curcumin: It  inhibits the growth and invasion of human monocytic leukemia. 
• Vitamin C: It  reduces the risk of leukemia, and may also be useful as chemotherapy for the blood cancer.
• Kenaf: It inhibits the proliferation of WEHI-3B leukemia cells.
• Gongura: It enhances cell death in leukemia cells.
• Moringa powder: It shows anti-cancer effects on leukemia cells. 
• Green seed extract: It appears to keep cancer in check in most of the chronic lymphocytic leukemia (CLL) patients.
• Probiotics: It helps in reducing the symptoms of gastrointestinal side effects due to chemotherapy, mainly among children with acute leukemia.
• Optimizing body function: Following integrative medicines are used for optimizing body functions in blood cancer (leukemia) patients:
• EGCG supplements: It shows a greater drop in their leukemia cell count. 
• Omega‐3 fatty acids: It improves red blood cell flexibility. 

Skin cancer: Following are the natural products used as integrative medicine showing efficacy among skin cancer patients:

• Cancer treatment: Integrative medicines used in skin cancer treatment includes:
• Vitamin B: It helps in reducing non-melanoma skin cancers.
• Vitamin C: It is used as an adjunct to chemotherapy for tumors in melanoma cells and causes a decrease in tumor-cell invasiveness and growth.
• Curcumin: It protects skin by quenching free radicals and reducing inflammation through nuclear factor-KB inhibition.
• Silymarin: It is a chemopreventive and pharmacologically safe agent which can be exploited or tested against skin cancer in the human system.
• Medical mushrooms: It is effective in healing the wounds after surgery in skin cancer patients.
• Reishi mushroom: It hydrates the skin. 
• Melatonin:  It is used to control melanoma growth and support basic and clinical studies on melatonin as a promising immunometabolic adjuvant for melanoma therapy.
• Vitamin E: It inhibits growth and survival of melanoma cells.

Management of side effects and promoting wellness: Following integrative medicines are used for reducing the side effects and enhancing the health outcome of the skin cancer patients:

• Grape seed extract: Chemicals found in grape seeds help ward off skin cancer due to regular exposure to the sun.
• Mistletoe: It helps in tumor progression and an improvement in psychosomatic self-regulation in patients with malignant melanoma.
• Ginger: It is capable of reducing side effects of chemotherapy such as vomiting and nausea. 
• Medical cannabis and cannabinoids: It provides relief from pain and other symptoms of skin cancer during and after chemotherapy.
• Curcumin: It inhibits skin cancer formation and prolong time to tumor onset.
• Melatonin: It suppresses ultraviolet (UV)-induced damage to skin cells and exerts strong antioxidant effects on UV-exposed cells. 
• Vitamin C: It  shows protective effects against the development of skin cancer. 
• Apigenin: It reduces the incidence and the size of the tumors in both chemical and UVB-induced skin carcinogenesis. 
• Boswellia: It reduces skin damage caused during radiation treatments for skin cancer.

Optimizing body function: Following integrative medicines are used for optimizing body functions in skin cancer patients:

• Green tea extract: It reverses, inhibits or slows down the process of skin carcinogenesis at one or at all the stages of carcinogenesis.  
• Milk thistle: It protects against UV-induced skin cancer.
• Silymarin: It  supplements sunscreen protection and provides additional anti-photocarcinogenic protection. 
• EGCG supplements: It  has anti-inflammatory and anticancer properties that may help prevent the development and growth of skin tumors. 
• Bilberry:  It acts as a protective strategy against skin cell damage induced by ROS.
• Ginkgo:  It has potent antioxidant protection, skin-soothing effects, increased skin-hydration, and significant anti-aging defense.
• Hawthorn: It  effectively inhibits the growth of melanoma cells.

Lung cancer: The integrative medication effective for lung cancer are discussed below:

Cancer treatment: Integrative medicines used in lung cancer treatment includes:

• Reishi mushroom:  It aids in improving oxygen utilization among lung cancer patients having asthma, bronchitis, pneumonia, chronic obstructive pulmonary disease (COPD) and similar conditions.
• Curcumin: It activates p38 pathway in lung cancer that induces cellular apoptosis. 
• Turkey tail mushroom: It is used as adjuvant therapy in strengthening the immune system of lung cancer patients.
• Polydatin: It suppresses proliferation and metastasis of non-small cell lung cancer cells.
• Boswellia serrata (BSE): It improves the lung function by enhancing the effectiveness of conventional leukotriene modifier medications. 

Management of side effects and promoting wellness:  Following integrative medicines are used to reduce the side effects and enhances the health outcome of skin cancer patients:

• Ginger: It helps in reducing the severity of nausea.
• Medical cannabis and cannabinoids: It provides relief from pain and other symptoms of lung cancer during and after chemotherapy.
• Curcumin: It helps to prevent lung nodules from growing larger in former and current smokers. 
• Melatonin: It is taken after complete resection to reduce lung cancer recurrence and mortality.
• Omega‐3 fatty acids: It improves nutritional status and inflammatory response in lung cancer patients.
• Beta-glucans: It exhibits direct anticancer effects and can suppress cancer proliferation in lung cancer patients.
• Astragalus: It improves lung functions, promotes healing, and reduces fatigue.
• Inositol: It reduces the tumor burden and prevents bronchial epithelial dysplasia in lung cancer patients. 
• Apigenin: It promotes TRAIL-mediated apoptosis in human lung cancer cells.
• Acetyl L-carnitine: It helps to improve appetite and increase energy levels after conventional treatment.
• Ginseng: It activates the processes of proliferation and death of lung cancer cells. 
• Epigallocatechin-gallate: It inhibits lung cancer cell proliferation. 
• Aloe vera: It reduces the severity of side effects among cancer patients.
• Fucosterol: It is used as phytomedicine showing  antiproliferative effects on human lung cancer cells.
• Lapacho: It induces apoptosis and inhibits telomerase activity in lung cancer patients.

Risk reduction: Following integrative medicines are used to reduce risk among lung cancer patients:

• Vitamin A: It helps in preventing the development of squamous and small cell carcinoma of the lung in smokers. 
• Vitamin C: It evolves 7% decrease in the risk of developing lung cancer. 
• Vitamin E: It acts as an antioxidant  and helps to prevent chronic lung conditions.
• Selenium supplements: It is effective for current smokers in preventing chronic lung conditions.
• Green seed extract:  It remodels a certain protein in the lung cancer cells, more likely to stick together and less likely to move.
• Tamarix Gallica: It inhibits invasion of human lung adenocarcinoma cells. 

Optimizing body function: Following integrative medicines are used for optimizing body functions in lung cancer patients:

• Curcumin: It modulates the activity of several transcription factors and their signaling pathways and enhances immune response in cancer patients.
• Reishi mushrooms: It is adjuvant therapy that may help strengthen the immune system in patients with lung cancer.
• Omega‐3 fatty acids: It helps the body to combat lung infections. 
• Beta-glucans: It is a potent immune-system enhancers in lung cancer patients. 
• Probiotics: It reduces respiratory infections and duration of infection with the common cold in lung cancer patients.
• Shiitake: It inhibits lung cancer cells. 
• Maitake mushrooms: It helps in improving the symptoms in advanced lung cancer patients.

C) Other Integrative Approaches:

Anti-cancer diet: The intake of a diet based on plant foods like vegetables, whole grains, beans and fruit and following some basic guidelines have effectively reduced cancer risk. The anticancer diet includes a plant-dependent diet that provides fiber intake to the body along with other vitamins, minerals and other antioxidants. Dietary interventions have resulted in improved outcomes in cancer treatment. Also, diet interventions have shown efficacy in overcoming the side effects caused by cancer treatment. The anticancer diet consists of high content food of phytochemicals with potent anticancer and anti-inflammatory properties. The food is an anticancer diet with the properties capable of blocking precancerous cells from developing into malignant cells by interfering directly with tumor cells and by preventing the generation of an inflammatory microenvironment that would sustain the progression of the tumors. Researchers have implicated that the use of natural products has been effective in improving the survival rate of cancer patients. Some of the common anticancer foods and nutrients involve flaxseeds, soy, garlic, berries, tomatoes, cruciferous vegetables, green tea, whole grains, turmeric, leafy green vegetables, grapes, beans, etc.

Dieticians or specialists recommend anti-cancer dietary guidelines for the prevention of cancer and reduce the risk of cancer. Some of the smart-eating policies as having been discussed below:

• Limiting the alcohol consumption and intake of foods with folic acid is recommended.
• Exercise regularly and reduce the intake of fat and sugar in food.
• Varieties of fruits and vegetables with about 1/2 cup every nine times a day are recommended. One cup of dark green vegetables and one cup of orange fruit and vegetables are recommended.
• Intake of fish and fish products is recommended two to three times a week while replacing with meats which contain high saturated fats.
• Intake of beans involving soybean products is essential, which is recommended three times a week to take the place of red meat and as a source of folic acid, fiber, and various phytochemicals.
• Several servings of whole-grain foods each day are recommended.
• Substitutes for foods with low calories, fat, and higher nutrients involving fibers is  recommended.
• Lean meats and low-fat dairy products and substitute canola and olive oil for butter, lard, and margarine high in trans fats are chosen.

The anti-cancer diet provided by Zen Integrative Oncology Wellness Protocol to help cancer patients are listed below:

Zen Anti Cancer Supplement Kit: It is a unique combination of clinically proven nutraceuticals that have displayed their efficiency in cancer treatment over the years. The individual should ensure to give a fighting chance by incorporating these nutraceuticals in their cancer treatment plan. Its benefits are:

• Anti-inflammation
• Anti-oxidants
• Immunity booster
• Natural pain killer
• Anti-anxiety and depression
• Metabolism regulation

Physical Fitness: Physical fitness is correlated with lowering the cancer risk and improving the survival rate after diagnosis and treatment. Exercises have been considered safe and feasible in terms of oncology, and many studies have revealed that it has improved the patients’ quality of life during and after cancer treatment (Sweegers et al., 2018). The positive aspects of physical fitness include enhancing cardiorespiratory fitness and muscular strength while improving body composition. Also, maintaining physical fitness by doing regular exercises helps regulate various side-effects of cancer treatment involving fatigue, nausea and improved psychological condition, and decreasing anxiety and depression levels. Several factors are responsible for the participation of cancer patients in exercise programs. The physical fitness of cancer patients is evolved by developing an exercise intervention that should consider the cancer patients’ obstacles and preferences, enabling them to choose the activities as per their preference. 

Emotional Wellness: Cancer patients suffer from psychosocial distress as soon as they are diagnosed with cancer before initiating the treatment approach. Increasing pain among cancer patients during and after the treatment has resulted in increased vulnerability in the patients’ cancer journey. The after-effects of the treatment, such as chemotherapy, surgery, and radiation in cancer treatment, have been a significant reason for deteriorating the mental health of cancer patients. Hence, emotional distress entirely depends upon the patient’s clinical condition, health, and prognosis. Therefore, there is a need to mitigate the emotional pain among the patients to improve their quality of life and increase their survival rate. Emotional wellness in cancer patients is promoted by helping them cope with their current situation by taking consideration from doctors, nurses, and allied health staff. The healthcare treatment team of the patient is one of the important sources of emotional support. The patients value the care being provided to them with empathy and per their desire. Hence, the nurses and oncologists mitigate the psychosocial concerns of the patients, which will help improve the patient’s well-being. Some of the emotional wellness support are discussed below:

Mindfulness: Mindfulness is the method of achieving a state of mind that is aware and in control. It helps reduce stress, improve physical health, and maintain harmony in life. It is considered an effective pain control method in cancer. Its practice has helped in reducing sleep disorders among cancer patients and survivors. 

Emotional and Spiritual Wellness: It involves the patients’ choice of gaining peace and comfort, adhering to emotional support from family members, and reducing the fear of death with the help of the healthcare team, social groups, families, volunteers, and religious personnel. It also helps in improving the quality of life of cancer patients. Spiritual care in cancer patients involves body-mind-community-spirit that includes various aspects such as peaceful, holistic, special, hospice, overall nursing care, palliative treatment, death education, etc. Spiritual wellness will add high value to the life of cancer patients, along with achieving peace of mind even during the drastic conditions of the cancer journey.

Guided imagery: These practices help reduce the cognitive, emotional stress, and fatigue among cancer patients that is evolved due to the integration of various treatment approaches. It mainly involves the inclusion of motivating sentences, music, and breathing and relaxation training. It is easy, convenient, and not restricted by patients’ activity levels. Guided imagery has helped cancer patients relax and has been effective in relieving the adverse side effects of chemotherapy, such as nausea, vomiting, anxiety, and depression. It is effective in improving the overall care for patients. 

Mind-body approaches: Mind-body approaches are the practices that have a major impact on the body functioning and improve the quality of life of cancer patients. It mainly enhances the changes in the brain’s evolving neurological effect showing effectiveness in managing chronic stress and understanding the actions of the brain towards well-being and improved health outcomes. It is considered one of the most healthy behavioral approaches for cancer patients that helps manage stress, improve quality of life, and achieve balance in life.

Healing Environment: There is a need to develop a person-centred healthcare environment for supporting the patients in building their physical and psychological well-being. A healing environment is related to the healthcare environment for cancer patients that helps establish therapeutic relationships between professionals and patients depending upon mutual trust, dignity, understanding, and sharing of human experiences. These factors will help promote a healing environment that involves care, and a degree of patient and family participation, thus enabling satisfaction levels among both patients and the healthcare team. The recovery of the patients does not entirely depend upon the medical factors, but it also depends upon the environmental and psychological aspects of the patients. Environmental factors play a vital role in the healing process after cancer treatment. Hence, a healing environment is a smart investment as it is cost-effective, increases staff efficiency, and reduces the patient’s hospital stay by making it less stressful.

Community Support: Finding an effective way to heal from such adverse events is being explored while exploring the internal and external resources that would help deal with the stressful conditions for longer durations. Community support, in this case, has been considered an essential factor that would help improve the lives of the cancer patients and help them to follow a path that would be effective in improving their survival in the cancer journey. The community support is capable of fulfilling the patients’ requirements, which helps develop optimal methods to cope with cancer adverse events. Excessive support in the patient’s life may result in causing negative effects on their daily activities that further integrate the chances of dependency. Hence, optimizing the community support has helped the patients develop a healthy approach to treatment and recovery. 

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