Prostate Cancer Treatment
In laboratory studies, vitamin D interferes with several cancer processes (Pdq Integrative 2017; Abu El Maaty 2017; Moukayed 2017). For instance, laboratory data suggest vitamin D can prevent cancer cells from metastasizing (Hsu 2011). Several animal studies have shown that under some conditions vitamin D can control tumor growth (Pdq Integrative 2017; Mordan-McCombs 2010; Ajibade 2014). In addition, vitamin D can boost the immune system, possibly helping it identify and destroy cancer cells (Pandolfi 2017).
Several studies have explored whether vitamin D can help fight prostate cancer in humans (Brandstedt 2016; Xie, Chen 2017). In one study, serum vitamin D levels were analyzed before diagnosis in 1,000 patients with prostate cancer. Those with higher vitamin D levels were significantly less likely to die from the disease (Mondul 2016). In another study, short-term supplementation with high-dose vitamin D for three to eight weeks lowered PSA levels (Wagner 2013). As part of another study, 52 men with low-risk prostate cancer being monitored with active surveillance took 4,000 IU vitamin D3 daily for one year. In 55% of the men, the prostate cancer was less extensive at the end of the study than at the beginning based on biopsy analysis (Marshall 2012). Vitamin D supplementation improved PSA test results in two additional studies (Srinivas 2009; Newsom-Davis 2009).
Hormone therapy can weaken the bones of prostate cancer patients, but supplemental vitamin D may help prevent fractures in these patients (Ottanelli 2015; Dueregger 2014). A study examining factors associated with bone preservation in prostate cancer patients using hormone therapies found that those taking vitamin D supplements experienced less bone loss in their lower-back vertebrae (Alibhai 2013).
Green tea and its catechins, including epigallocatechin gallate or EGCG, may be helpful in fighting prostate cancer. In laboratory studies, EGCG slowed prostate tumor growth and caused cancer cells to die (Li 2014; Lin 2015). EGCG may also interfere with hormone signaling in prostate cancer cells (Ren 2000; Siddiqui 2011; Lee 2012).
Several human trials have suggested green tea and its catechins can prevent prostate cancer, particularly in men with high-grade prostatic intraepithelial neoplasia, or PIN, a precancerous condition (Pdq Integrative 2017; Jacob 2017). In a placebo-controlled trial, PSA levels decreased in men diagnosed with high-grade PIN taking 400 mg EGCG daily (Kumar 2015); furthermore, no toxic effects were seen after one year of EGCG supplementation at this dose (Kumar 2016). In a meta-analysis of multiple studies in men with high-grade PIN, taking green tea catechins reduced the rate of progression to prostate cancer from 23.1% to 7.6% (Cui 2017).
In a randomized trial, 113 men diagnosed with prostate cancer were assigned to drink six cups per day of green tea, black tea, or water for at least three weeks prior to prostatectomy. PSA levels significantly decreased in the group taking green tea (Henning 2015). In another trial, taking a green tea catechin supplement providing 800 mg EGCG daily was found to decrease levels of PSA and some other cancer markers in the blood in men with biopsy-confirmed prostate cancer awaiting prostatectomy (McLarty 2009).
Fish Oil and Omega-3 Fatty Acids
Oily fish are high in omega-3 polyunsaturated fatty acids (Ruxton 2004). These fatty acids have many health benefits and may even slow the growth of prostate cancer (Li 2014; Berquin 2011; Aucoin 2017). In laboratory and animal studies, omega-3 fatty acids were found to inhibit inflammation, interfere with blood vessel growth in tumors, and cause cancer cells to die (Spencer 2009; Gu 2013). Mice with prostate cancer whose only source of fat was fish oil survived longer than control mice fed diets with olive oil, corn oil, or animal fat (Lloyd 2013). Further analysis found that omega-3 fatty acids had beneficial effects on several types of cancer-fighting immune cells in the mice (Liang 2016).
In a study that included more than 290,000 men, those who reported high fish and high omega-3 fatty acid intake on diet questionnaires at the beginning of the study were significantly less likely to die from prostate cancer during approximately 20 years of follow up (Bosire 2013). In a randomized trial, men scheduled for radical prostatectomy ate either a low-fat diet supplemented with 5 grams of fish oil daily or a traditional Western diet. Prostate cancer cells exposed to blood taken from the men eating the low-fat plus fish oil diet showed decreased growth in the laboratory (Aronson 2011). A second analysis of this same study found that pro-inflammatory marker levels were decreased and scores on a prognostic test were more favorable in the patients eating the low-fat plus fish oil diet (Galet 2014). In a study in men with low-risk prostate cancer undergoing active surveillance, higher tumor levels of omega-3 fatty acids, particularly the marine omega-3 fatty acid eicosapentaenoic acid (EPA), were associated with reduced risk of prostate cancer progression (Moreel 2014).
Flaxseed is a plant source of omega-3 fatty acids and fiber, as well as a class of polyphenols called lignans that have weak estrogenic activity (Kajla 2015). In one study, 25 men awaiting surgery for prostate cancer ate a low-fat diet supplemented with 30 grams of ground flaxseeds per day. Several tests indicated that the diet may have reduced cancer cell survival and proliferation (Demark-Wahnefried 2001). In a larger follow-up study, a similar group of patients ate either 30 grams ground flaxseeds per day, a low-fat diet, a low-fat diet plus 30 grams ground flaxseeds per day, or a control diet. Flaxseed supplementation, even without the context of a low-fat diet, was associated with molecular changes that may indicate that cancer cells were dividing more slowly (Demark-Wahnefried 2008).
As described in the “Dietary and Lifestyle Considerations” section, lycopene may help reduce risks of prostate cancer. Beneficial cancer-fighting effects of lycopene have been demonstrated in laboratory studies (Pdq Integrative 2017; Lin 2015). Small clinical studies in humans have shown that supplemental lycopene is safe and may reduce prostate cancer cell activity (Pdq Integrative 2017; Kumar 2008).
In a randomized controlled trial, men being treated with surgical removal of the testicles had a more consistent decrease in PSA levels if they were taking 4 mg per day of supplemental lycopene (Ansari 2003). Another randomized trial found that taking 30 mg lycopene per day reduced levels of markers of tumor growth in men newly diagnosed with localized prostate cancer (Kucuk 2001). In addition, men with intermediate-risk prostate cancer who ate tomato products providing 30 mg lycopene daily had significant decreases in PSA levels after three weeks (Paur 2017).
Pomegranate contains a number of compounds that combat free radicals, and extracts from pomegranate interfere with cancer cell division in laboratory research (Pdq Integrative 2017). In a study designed to simulate consumption of one to two pomegranate fruits per day in an average adult human, mice injected with prostate cancer cells drank either plain water or water with pomegranate extract. Tumor onset was later and tumor growth was slower in the mice receiving the pomegranate extract (Malik 2005). In a study using experimental mice bred to be highly susceptible to prostate cancer, the same dose of pomegranate extract prevented metastasis and increased survival (Adhami 2012). Several other animal studies have shown similar results (Seeram 2007; Sartippour 2008; Albrecht 2004).
Pomegranate products have also been tested in human studies. In one trial, the average PSA doubling time increased from 15 months to 54 months in men with rising PSA levels after surgery or radiation therapy who drank eight ounces of pomegranate juice daily. Prostate cancer cells exposed to blood taken from patients treated in this study did not divide as rapidly and were more likely to die (Pantuck 2006). A randomized trial in a similar patient population found that doses of 1 and 3 grams of pomegranate extract per day extended PSA doubling time by 58% and 43%, respectively, an effect that was statistically the same for the two doses (Paller 2013).
Cruciferous Vegetable Isothiocyanates
Cruciferous vegetables such as cabbage, broccoli, cauliflower, collard greens, arugula, Brussels sprouts, and kale contain phytochemicals called glucosinolates. During food preparation, chewing, and digestion, glucosinolates are broken down into isothiocyanatets (eg, sulforaphane) and other bioactive compounds called indoles (eg, indole-3-carbinol). The cruciferous-vegetable-breakdown products have some compelling anti-prostate-cancer properties (Novio 2016; Watson 2013). Epidemiological studies have found correlations between greater intake of cruciferous vegetables and reduced risk of prostate cancer (Watson 2013). A small clinical study in which 20 men with prostate cancer took an isothiocyanate-rich broccoli extract for up to 20 weeks showed that PSA doubling time increased during treatment (Alumkal 2015). A meta-analysis of observational studies found that cruciferous vegetable consumption was associated with a roughly 20% relative prostate cancer risk reduction among men who ate the most cruciferous vegetables versus those who ate the least (Liu 2012). As of the time of this writing in early 2018, four clinical trials examining different cruciferous vegetable derivatives or preparations are pending publication of results.
Cranberries are a rich source of phytonutrients known to boost the immune system and fight infection, and laboratory and clinical data suggest cranberry products may be useful for cancer patients (Weh 2016). In several laboratory studies, various preparations of cranberry juice have been shown to interfere with cancer cell division and signals that boost cancer growth (Weh 2016; Deziel 2012; Deziel 2010). In an animal model of prostate cancer, a purified proanthocyanidin-rich extract from cranberries significantly slowed prostate tumor growth (Ferguson 2006).
In a controlled clinical trial, 64 participants scheduled for radical prostatectomy took either 1,500 mg per day of cranberry fruit powder or placebo for at least 21 days prior to surgery. Average PSA levels decreased by 22.5% in the group taking cranberry and increased by 0.9% in the placebo group (Student 2016).
Some studies have addressed whether cranberry can help relieve urinary symptoms in men treated for prostate cancer. Urinary tract infections are a common side effect of radiation therapy (Flannigan 2014; Bonetta 2012). Cranberry extract can interfere with the ability of bacteria to stick to tissue in the urinary tract (Weh 2016; Sobota 1984; Hisano 2012). In a randomized controlled trial in 370 men undergoing radiation therapy, those receiving 200 mg cranberry extract daily had a lower rate of urinary tract infections than those receiving placebo (8.7% vs. 24.2%) (Bonetta 2012). A large follow-up study confirmed these results in a group of 924 participants (Bonetta 2017). In a separate study, cranberry extracts protected men being treated with radiation therapy from another common side effect—inflammation of the bladder (Hamilton 2015).
Soy isoflavones such as genistein have been studied extensively for their anti-inflammatory and estrogen-modulating effects (Danciu 2017). Laboratory data on prostate cancer cells suggest isoflavones may reduce inflammation and interfere with signals that promote blood vessel growth in tumors (Swami 2009; Rabiau 2010). Genistein has been shown to slow prostate tumor cell proliferation in laboratory and animal models (Ajdzanovic 2013; Wang 2004; El Touny 2009). Findings from other studies suggest isoflavones may make prostate cancer cells more sensitive to radiation therapy (Raffoul 2007; Singh-Gupta 2010).
In a randomized controlled trial, 32 patients with rising PSA levels after prostate cancer treatment added two slices of soy-enriched bread, providing 34 mg of isoflavones per slice, or a placebo bread to their daily diet. Reduced levels of markers of inflammation and suppressed cancer-promoting immune activity were seen in those receiving isoflavones in their bread (Lesinski 2015). In another randomized trial including 54 patients scheduled for prostatectomy, those who received 30 mg genistein per day had a 7.8% drop in PSA levels versus a 4.4% increase in the placebo group (Lazarevic 2011). Two small open trials using isoflavone-containing soy beverages noted reductions in PSA level increases in participants with rising post-treatment PSA levels (Kwan 2010; Pendleton 2008).
Some clinical trials have found that isoflavones do not affect PSA levels or other health parameters (deVere White 2010; Hamilton-Reeves 2013). Inconsistencies in preparations, doses, participant characteristics, and treatment durations make it difficult to draw conclusions. Future research into the effects of soy and isoflavones on prostate cancer outcomes is needed.
Modified Citrus Pectin
Pectin is an indigestible carbohydrate that is especially abundant in the peels and pulp of citrus fruits. Modified citrus pectin (MCP) is pectin that has been chemically modified to break into smaller carbohydrate chains that can be absorbed into the blood. Studies have shown that these small bits of MCP inhibit a molecule called galectin-3. Cancer cells use galectin-3 during metastasis, and inhibiting galectin-3 may impede cancer cells’ ability to spread (Leclere 2013; Zhang 2018; Jiang 2013).
Indeed, findings from a study using a rat model of prostate cancer suggest oral MCP may reduce metastases. Although nearly all untreated rats had metastases after 30 days, only about half of the rats drinking water containing MCP had metastases (Pienta 1995).
In a small clinical trial, 10 men with rising PSA levels after treatment for prostate cancer received 14.4 grams per day of MCP for 12 months; PSA doubling times increased in seven of the 10 men (Guess 2003). Another open trial tested the effects of MCP supplementation, at 15 grams per day, in participants with a variety of advanced solid cancers. MCP led to improved quality of life and disease stabilization in 20.7% of the 29 participants who completed eight weeks of supplementation. One participant with metastatic prostate cancer had a remarkable response, with a 50% decreased PSA level, improved quality of life, and decreased pain at 16 weeks (Azémar 2007). An ongoing clinical trial is evaluating the effect of MCP, at a dose of 4.8 grams three times per day, on PSA levels (Keizman 2017).
Laboratory research suggests MCP may prevent tumor growth and spread by interfering with cell-cell interaction and adherence (Leclere 2013). MCP and a similar product called fractionated pectin powder have also been shown to cause cell death in prostate cancer cell cultures (Jackson 2007; Yan 2010).
Curcumin, a carotenoid pigment extracted from the spice turmeric, has well-established anti-inflammatory and oxidative stress-reducing effects. In laboratory studies, curcumin interfered with cancer growth signals, decreased androgen receptor activity, reduced production of PSA, and slowed tumor growth (Li 2014; Lin 2015; Goel 2010; Rivera 2017). In one trial, 36 patients with castration-resistant prostate cancer and rising PSA levels were given 6,000 mg curcumin per day while undergoing treatment with docetaxel and prednisone. Positive PSA responses were noted in 59% of participants (Mahammedi 2016). Another study with 85 participants found that a combination of curcumin and soy isoflavones markedly reduced PSA levels in men with high PSA levels and negative biopsies (Ide 2010).
Healthy prostate cells accumulate zinc to accomplish their normal cellular functions. In contrast, prostate cancer cells have depleted zinc stores, which makes them less susceptible to cell death (Costello 2016; Eidelman 2017; Franz 2013). When prostate cancer cells are treated with zinc in the laboratory, they begin to die (Feng 2002). In a group of over 35,000 men, those taking higher amounts of supplemental zinc were observed to be significantly less likely to be diagnosed with advanced prostate cancer (Gonzalez 2009). Another observational study in 525 men noted that those with higher dietary zinc intake around the time of their prostate cancer diagnosis had a lower risk of dying from prostate cancer (Epstein 2011).
Melatonin, a hormone best known for its role in regulating sleep, is also emerging as a promising anti-cancer agent. Evidence to date has shown that melatonin can interfere with cancer initiation, progression, and metastasis (Reiter 2017). In an observational study, men with higher levels of melatonin metabolites in their urine were found to be significantly less likely to have prostate cancer, especially advanced prostate cancer (Tai 2016). When rodents with prostate cancer were treated with supplemental melatonin, blood vessel growth was inhibited and the tumors grew more slowly (Paroni 2014; Xi 2001; Siu 2002; Mayo 2017). Melatonin may fight prostate cancer by interfering with androgen receptor signaling (Reiter 2017). Melatonin has also been shown to decrease glucose metabolism in prostate cancer cells, reducing cancer cells’ ATP production (ATP is a key cellular-energy-storage compound) (Hevia 2017). Melatonin may also enhance cancer cells’ sensitivity to conventional anti-cancer drugs, possibly complementing standard therapy (Reiter 2017).
Milk Thistle and Silymarin
Milk thistle (Silybum marianum) has been used for thousands of years as an herbal remedy for liver disorders. One of the main active ingredients in the seeds and fruit of milk thistle is a flavonoid complex called silymarin (Vue 2016; Abenavoli 2010; Vaknin 2008). Many studies have tested the effects of silymarin on rodents with prostate cancer and on prostate cancer cells in the laboratory. For example, one component of silymarin, called silibinin, reduced the creation of new blood vessels in tumors and slowed tumor growth in mice with prostate cancer (Deep 2017). In another study, silibinin made prostate tumors in mice more sensitive to the effects of radiation yet protected healthy tissues from radiation damage (Nambiar 2015).
Silibinin is being tested in clinical trials for breast cancer (Lazzeroni 2016), hepatitis C infection (Braun 2015), and liver cancer (Siegel 2014). In six patients with prostate cancer awaiting prostatectomy, taking 13 grams daily of a preparation of silibinin led to high levels of silibinin in the blood; however, levels were very low in the prostate tissue obtained during surgery (Flaig 2010). Recent studies have explored variations in the silibinin compound that may be more potent and may reach the prostate tissue more effectively (Vue 2017; Manivannan 2017).
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