Natural Supplements for Brain Tumors

Brain Tumors and Conventional Medicine

The National Cancer Institute (NCI) and the American Cancer Society (ACS) estimate that 22,020 primary malignant brain tumors will be diagnosed in 2010 (Porter KR et al 2010). The American Brain Tumor Association, since they count both malignant and benign brain tumors, predicts twice as many cases (Jemel A et al 2008).

Secondary brain tumors, which originate elsewhere in the body, outnumber primary tumors four-to-one, so add another 100,000 cases a year to get an idea of the total number of people who will be diagnosed with brain cancer each year (Davis FG et al 2001).

The medical treatment of primary brain tumors typically consists of two steps: surgical excision, followed by combined radiation and chemotherapy. For advanced or high-grade tumors the benefit of these therapies seems small.

“After conventional treatments, the survival rate for patients with astrocytomas or glioblastomas is about 50% at 1 year, 25% at 2 years, and 10 to 15% at 5 years” (Online Merck Manual, accessed Oct, 2010).

Thus many patients wisely seek complementary therapies hoping to improve their odds. The risk factors for brain tumor are almost unknown, though there are hints that suggest early exposure to certain chemicals might play a role.

In 2010 the Fred Hutchinson Cancer Research Center in Seattle reported that children who develop brain tumors are likely both to have been exposed to higher than average amounts of pesticides and to have been born with a reduced ability to detoxify these chemicals (Barrett JR 2010, Nielsen SS et al 2010).

Other studies also point to chemical exposure as a potential risk factor. The children of women who had high exposure to beauty-products are at increased risk for brain tumors (Efird JT et al 2005). Personal hair dye use increases risk in one study. Using brown hair dye for 20 years, for example, almost quadrupled risk of glioma in women (Bluhm EC et al 2007).

Individuals who engage in a hobby that involves using glue are at 18 times the average risk (Spinelli V et al 2009). A 2009 review found that people who used cell phones for at least 10 years had a 2.4-fold greater risk of developing an acoustic neuroma in the ear to which they routinely held their phone, but had no change in risk for other types of cancer (Han YY et al 2009).

The idea that nitrosamines in processed meats may increase the risk of glioma has been circulating for several decades (Michaud DS et al 2009), yet a July 2010 paper found only a modest increase in risk in people who ate large amounts of nitrosamines compared to those who ate very little (Dubrow R et al 2010).

There are no tests to predict the risk of brain cancer, or steps we can take to prevent it. Our focus is on preventing recurrence or at least slowing down the disease.

Natural Supplements for Brain Tumors

Vitamin D

Vitamin D deficiency that occurred before birth may have set the stage for brain tumor formation later in life. Vitamin D deficiency during gestation causes long-term effects on brain development (Levenson CW et al 2008).

Vitamin D remains important after birth, as it activates chemical pathways, in particular the sphingomyelin pathway, which kills glioblastoma cells (Magrassi L et al 1998). Vitamin D, the chemical form of vitamin D made in the skin and sold as a nutritional supplement, calcitriol (1,25-dihydroxy vitamin D), the active form of vitamin D, and various chemical analogs and metabolites of vitamin D, have all been shown to inhibit growth and trigger apoptosis in neuroblastoma and glioma cells (Naveilhan P et al 1994, Baudet C et al 1996, Elias J et al 2003, van Ginkel PR et al 2007).

A 2009 report on brain tumor death statistics from Finland alludes to the benefit of vitamin D. Mortality from brain tumors is highest in patients who were diagnosed and underwent surgery during the late winter, particularly from February to March. This is the time of year when vitamin D levels are at their lowest (Hakko H et al 2009).

Similar seasonal variations in cancer survival rates are seen for lung (Porojnicu AC et al 2007), breast (Stajner I et al 2010), and colon cancer (Robinson D 2010). The explanation tendered in all these studies is that in the winter people have lower vitamin D levels and are less capable of fighting the cancer.

Another data analysis from Spain revealed a direct correlation between latitude and brain cancer incidence. The higher the latitude, that is the further from the equator someone lives, the greater their risk for brain cancer (Grant WB et al 2007). The further people live from the equator, the lower their vitamin D levels (Genuis SJ et al 2009).

Melatonin

Melatonin is often suggested for treating various forms of cancer, particularly breast, lung and colorectal cancers. Lissoni has conducted repeated studies demonstrating that patients with advanced cancers given melatonin survive longer than patients receiving a placebo (Lissoni P et al 2007).

There is growing evidence suggesting melatonin may be useful in treating primary brain tumors. An in vitro experiment showed that melatonin, at physiologic concentrations, inhibits growth of neuroblastoma cells (Cos S et al 1996).

A 2006 paper published in Cancer Research reported that melatonin stopped the growth of gliomas that had been implanted into rats (Martín V et al 2006). As a result, some researchers suggest melatonin might be useful in treating glioma (Wion D et al 2006).

The strongest evidence for the use of melatonin in brain cancer is in treating pituitary tumors. Melatonin given to rats inhibits the chemical-induced formation of pituitary tumors (Gao L 2001). Giving melatonin to rats with pituitary tumors halts tumor growth and triggers apoptosis, especially if the tumor secretes prolactin (Yang QH et al 2006).

Vitamins and Minerals

Folic Acid and 5-MTHF

To be of use in the body, natural folate from food and folic acid from supplements must be converted into the active form, 5-MTHF (5-methyltetrahydrofolate), by the enzyme 5,10-methylenetetrahydrofolate reductase (MTHFR). In certain people the gene that codes for this enzyme produces a less effective enzyme.

In some studies, the risk for glioma in these people is increased by about 23% while meningioma risk is more than doubled (Sirachainan N et al 2008, Bethke L et al 2008, Kafadar AM et al 2006).

People can compensate for this genetic problem by taking a supplement of active 5-MTHF and bypassing the need for the MTHFR enzyme. A German study compared survival times of patients with glioblastoma multiforme with their MTHFR gene variants.

Those patients who were best able to convert folate into its active form survived for about 13 months. Those with the less effective MTHFR genes survived for only seven months (Linnebank M et al 2008). This suggests that supplementing with the active form of folate might be helpful.

Selenium

Selenium is another antioxidant that patients with brain tumors should consider. Many oncologists fear that any nutritional supplement classified as an antioxidant will interfere with the ability of radiation or chemotherapy to kill cancer cells.

Though this theory sounds logical, there is little published evidence to support it. In the case of selenium, a 2004 paper in the journal Anticancer Research, reports a “radiosensitizing effect” on glioma cells (Schueller P et al 2004).

Exposing brain cancer cells to selenium makes them more sensitive to, and more likely to die after, radiation therapy. Selenium also inhibits growth and invasion, and induces apoptosis in various types of brain tumor cells, including malignant cell lines (Sundaram N et al 2000, Rooprai HK et al 2007).

Vitamin E

Vitamin E is another antioxidant of particular interest in connection with brain cancer. According to a 2005 study, alpha-tocopherol-succinate enhances chemotherapy treatment of drug resistant glioblastoma cells, increasing effectiveness (Kang YH et al 2005).

A researcher from Tufts University described the use of vitamin E in treating glioblastoma multiforme in a 2004 article in the Journal of Nutrition.Glioblastoma multiforme is the most common and aggressive brain cancer in humans and resists all forms of therapy.

Vitamin E (succinate) induces apoptosis in glioblastoma cells in a dose-related manner; we find that a 48-h exposure to 50 micromol/L vitamin E results in a 15% increase in apoptosis in the glioblastoma cells over control. Pretreatment with vitamin E may have a potential role in sensitizing glioblastoma to radiotherapy” (Borek C 2004).

Botanical or Herbal Extracts

Berberine

Berberine is an alkaloid found in various different medicinal herbs. Probably the most popular herb containing berberine is Goldenseal (Hydrastis Canadensis), followed by Oregon grape (Berberis aquifolium) and Chinese Isatis (Isatis tinctoria).

A 1990 study tested the tumor-killing effect of berberine compared to the chemotherapy drug BCNU (carmustine) in both glioma cell cultures and in rodents implanted with tumors. Berberine alone produced a 91% kill rate in cell cultures, compared to 43% for BCNU.

Combining berberine with BCNU yielded a kill rate of 97% (Zhang, RX et al 1990). A 1994 paper described in vitro experiments using berberine alone, or in combination with laser treatments, on glioma cells. The combination was especially effective, suggesting “the possibility of berberine as a photosensitive agent” (Chen KT et al 1994).

A 2004 paper tells us that berberine increases the benefit of radiation treatment by making glioblastoma cells more sensitive to radiation damage, without affecting healthy brain cells (Wallace J et al 2004).

A similar effect is seen in lung cancer wherein berberine sensitizes lung tumor cells to radiation (Peng PL et al 2008, Liu Y et al 2008). Berberine slows the spread of nasopharyngeal carcinoma, decreasing motility of the tumor cells (Liu SJ et al 2008).

Berberine inhibits gene expression and enzyme activity necessary for glioblastoma and astrocytoma growth (Wang DY et al 2002). It also inhibits an enzyme called arylamine N-acetyltransferase (NAT). NAT may initiate cancer and has been correlated with the carcinogenic effect of heterocyclic aromatic amines, the kind of chemicals formed when red meat is cooked (Hung CF et al 2000).

The scientific understanding of how berberine actually works continues to advance. A 2007 description suggested that berberine acts “through several ways, such as regulating apoptotic gene expression, suppressing the formation of tumor angiogenesis [and] blocking signal transduction pathway” (Yang J et al 2007).

A 2008 study explained that berberine triggers apoptosis in glioblastoma cells through the mitochondrial caspases pathway (Eom KS et al 2008). As of 2009, research reported that berberine kills glioma cells through several mechanisms: “Cytotoxicity is attributable to apoptosis mainly through induced G2/M-arrested cells, in an ER-dependent manner, via a mitochondria-dependent caspase pathway regulated by Bax and Bcl-2” (Chen TC et al 2009).

In 2010 explanations for action expanded to include the inhibition of NF-KappaB and the reduction of a series of chemicals that help cancer cells to survive, including one called survivin (Pazhang Y et al 2010).

Survivin slows down apoptosis, allowing tumor cells to survive. Healthy cells do not produce survivin but cancer cells typically do (Pandey MK et al 2008). Several hundred published papers suggest that berberine is effective against not only brain tumors but a range of cancers.

In the last few months alone, several interesting papers have been published. Among their conclusions are: berberine prevents cell growth and induces apoptosis in breast cancer cells (Kim JB et al 2010; Patil JB et al 2010); berberine is cytotoxic to cervical cancer cells (Lu B et al 2010); berberine inhibits cell growth in pancreatic cancer cells by inducing DNA damage (Pinto-Garcia L et al 2010); and berberine triggers cellular suicide in tongue cancer (Ho YT et al 2009).

Boswellia

The resin from Boswellia serrata also has an important role in treating brain cancer. Boswellia is commonly used for treating inflammation because it acts as an NF-KappaB inhibitor.

It is neuroprotective, anti-inflammatory, and reduces anxiety (Moussaieff A et al 2009). One important use of boswellia is in the treatment of traumatic brain injuries. Boswellia decreases the brain swelling from glioblastoma, allowing a decrease in the use of prednisone and thus reducing its side effects (Janssen G et al 2000).

Boswellia inhibits hippocampal neurodegeneration and exerts a beneficial effect on functional outcome after closed head injury, as evidenced by reduced neurological severity scores and improved cognitive ability in an object recognition test (Moussaieff A et al 2008). A 2006 paper reports that Boswellia serrata was gaining importance in the treatment of edema surrounding tumors and other chronic inflammatory diseases.

This study suggested that boswellia might be considered as an alternative to corticosteroids in reducing cerebral peritumoral edema (Weber CC et al 2006). Finding ways to reduce or replace steroid use in the treatment of brain tumors is important, since steroid drugs may protect brain tumor cells.

According to a 2000 article in Neuroscience,

“glucocorticoids are often used in the treatment of gliomas to relieve cerebral oedema, the inhibition of apoptosis by these compounds could potentially interfere with the efficacy of chemotherapeutic drugs.” (Gorman AM et al 2000)

A 2006 study reported that steroids interfere with glioma cell apoptosis (Ní Chonghaile T et al 2006). Steroids block the cancer-killing action of camptothecin, a chemotherapy drug used in treating glioma (Qian YH et al 2009). Boswellia may be doubly useful for primary brain tumors.

Studies published in 2000 (Winking M et al 2000) and 2002 (Park YS et al 2002) tell us that in addition to helping reduce cerebral swelling around the tumor, boswellia also kills glioblastoma cells in a dose-dependent manner. Boswellia is also useful for treating secondary brain tumors.

In 2007 researchers reported using boswellia to treat a patient with breast cancer metastasis to the brain. Familiar with the German research on using boswellia in the treatment of primary brain tumors, the team tried it with these secondary brain tumors and reported benefit. After ten weeks of boswellia treatment in combination with radiation treatment, all signs of brain metastases on the patient’s CT scans had disappeared (Flavin DF 2007).

Curcumin

Curcumin is extracted from turmeric rhizomes (Curcuma longa), a plant that has been eaten for thousands of years. As of this writing, the National Institute of Health’s website, PubMed, lists 1,335 published papers on curcumin and cancer in the peer-reviewed scientific literature.

A growing number of these studies focus specifically on using curcumin in connection with brain cancer. A 2006 paper tells us curcumin suppresses growth of glioblastoma by triggering the apoptotic pathways that destroy glioblastoma cells (Karmakar S et al 2006).

Curcumin turns off the signals in the cells that protect glioblastoma cells from apoptosis, allowing the suicide process to destroy the cancer cells (Karmakar S et al 2007, Luthra PM et al 2009). Curcumin has a similar action against other brain tumor types, including meduloblastoma cells and pituitary cancers (Bangaru ML et al 2010, Elamin MH et al 2010). Curcumin inhibits pituitary cancer from forming (Schaaf C et al 2010). It also slows growth of pituitary tumors and inhibits production of excess pituitary hormones by tumors (Schaaf C et al 2009, Miller M et al 2008).

Curcumin’s mechanisms of action are complex. It acts through multiple pathways, interfering with cancer growth and stimulating cancer destruction (Choi BH et al 2010). Curcumin decreases Glial cell line-derived neurotrophic factor (GDNF), a chemical that promotes tumor migration and invasion (Lu DY et al 2010, Song H et al 2006). It also acts as an angiogenesis inhibitor (Perry MC et al 2010). An article in Brain Research confirms that curcumin crosses the blood brain barrier; thus reaching the brain and any tumor cells there (Purkayastha S et al 2009).

A study published in the Journal of Neurochemistry reported that curcumin sensitized glioma cells to several of the chemotherapy drugs often utilized to treat brain cancers (cisplatin, etoposide, camptothecin, and doxorubicin) as well as to radiation.

“These findings support a role for curcumin as an adjunct to traditional chemotherapy and radiation in the treatment of brain cancer” (Dhandapani KM et al 2007).

Curcumin has long been known for poor bioavailability, requiring high doses to achieve desired blood levels. A novel curcumin formulation, BCM-95, has been developed. It delivers up to seven times more bioactive curcumin to the blood than earlier curcumin formulations.

Human evidence for the increased bioavailability of BCM-95 was published in a 2008 study in the Indian Journal of Pharmaceutical Science (Antony B et al 2008). An earlier animal trial was published in Spice India in 2006 (Merina B et al 2006).

Other Natural Ingredients

Quercetin

Quercetin enhances glioma cell death (Siegelin MD et al 2009). While killing cancer cells, quercetin protects healthy brain cells (Braganhol E et al 2006). An especially interesting study tested a combination of quercetin and the chemotherapy drug temozolomide (Temodar®) on astrocytoma tumor cells.

Temozolomide is commonly used for the treatment of glioma in conjunction with radiation therapy. This drug typically kills brain tumor cells by triggering a process called autophagy, while quercetin promotes necrosis in a dose dependent manner.

This study reported for the first time that quercetin combined with temozolomide was much more effective in inducing apoptosis, programmed cell death, in glioma cells than was either substance alone. To quote the authors,

“Our results indicate that quercetin acts in synergy with temozolomide and when used in combination rather than in separate pharmacological application, both drugs are more effective in programmed cell death induction. Temozolomide administered with quercetin seems to be a potent and promising combination which might be useful in glioma therapy” (Jakubowicz-Gil J, et al 2010).

Resveratrol

Resveratrol also strongly inhibits brain tumor cells (Leone S et al 2008, Shao J et al 2009, Gagliano N et al 2010). Quercetin and resveratrol, when taken together

“presented a strong synergism in inducing senescence-like growth arrest. These results suggest that combining these polyphenols can potentiate their antitumoral activity, thereby reducing the therapeutic concentration needed for glioma treatment” (Zamin LL et al 2009).

Green Tea and Coffee

People who drink five cups per day of tea or coffee are 40% less likely to get glioma (Holick CN et al 2010). A 2006 study informed us that the EGCG in green tea reduces the radio-resistance of glioblastoma cells potentially increasing the benefit of the standard radiation and chemotherapy treatment of this cancer (Karmakar S et al 2006).

Caffeine, found in significant quantities in coffee and green tea, inhibits migration of glioblastoma cells and increases survival (Kang SS et al 2010). It also makes glioma cells more sensitive to ionizing radiation and chemotherapy (Sinn B et al 2010).

Caffeine enhances the effect of temozolomide in radiation treatments (Chalmers AJ et al 2009). At least part of the explanation for these benefits is that coffee is a peroxisome proliferator-activated receptor (PPAR) gamma agonist (Choi SY et al 2009). PPAR gamma agonists inhibit brain tumor growth and possibly even brain cancer stem cells (Grommes C et al 2010, Chearwae W 2008).

Sulforaphane

Sulforaphane is one of the active compounds in cruciferous vegetables, especially broccoli, responsible for their anti-cancer action. Sulforaphane activates “multiple molecular mechanisms for apoptosis in glioblastoma cells following treatment” (Karmakar S et al 2006).

Resveratrol and sulforaphane act synergistically against brain tumor cells. A 2010 article states,

“Combination treatment with resveratrol and sulforaphane inhibits cell proliferation and migration, and reduces cell viability. Resveratrol and sulforaphane, may be a viable approach for the treatment of glioma.” (Jiang H et al 2010)

A Diet for Brain Cancer

There are two specific diets that should be considered for treating brain tumors, either separately or in combination.

The Ketogenic Diet

The Ketogenic Diet is a very high fat, high protein, and extremely low carbohydrate diet typically used to treat epilepsy (Porta N et al 2009).

Without carbohydrates, the body shifts from using glucose to ketones for energy. Healthy brain cells can utilize either glucose or ketones. Brain tumor cells can only burn glucose. The theory is that switching to ketones for energy starves brain tumor cells.

A 2007 study tested this theory on mice implanted with malignant brain tumors. The treatment group was fed a drink high in fat and protein that was designed to cause ketosis in children with epilepsy, and the control group was fed a low fat high carbohydrate diet.

The ketone-producing diet decreased growth of the brain tumors from 35 to 65%, depending on the tumor line, and significantly enhanced health and survival compared to the control group, which was on the low fat, high carbohydrate diet (Zhou W et al 2007).

In 1995 doctors from Case Western Reserve reported treating two young girls suffering from astrocytomas with low-carbohydrate ketogenic diets. One of the girls had a favorable clinical response without reported disease progression for 12 months at the time of publication (Nebeling LC et al 1995).

In April 2010, a case report was published describing an older female patient treated for glioblastoma multiforme with an initial 2-day water fast followed by a ketogenic diet and then simply a caloric-restricted diet. The tumor regressed during treatment, getting smaller on subsequent scans from January until July, at which point the patient stopped following the diet.

The tumor returned ten weeks later (Zuccoli G et al 2010). At this point the evidence supporting the management of brain cancer through a ketogenic diet is intriguing, and the risks are minimal (Seyfried TN et al 2010).

Caloric Restriction

Caloric restriction also appears to slow brain tumor growth. A 2002 study reported experiments on mice with brain tumors. Compared to mice that were not restricted in their food intake, the brain tumors in mice on a calorie-restricted diet grew slower, were less dense, and displayed less angiogenesis (building new blood vessels to feed the tumor).

The tumor cells in the caloric-restricted mice were more likely to undergo apoptosis (Mukherjee P et al 2002). A July 2010 paper confirmed the benefit in mice with glioblastoma multiforme. Caloric restriction was effective in reducing malignant brain tumor growth and invasion (Shelton LM et al 2010).

Caloric restriction, although it may put the body into ketosis, is thought to act differently than the ketogenic diet. Hunger puts a mild stress on the body. Mild stress is, in turn, hypothesized to create a hormetic reaction awakening protective mechanisms within the body, stimulating the individual cells to fight the cancer (Kouda K et al 2010).

Researchers at Boston College are now investigating the simultaneous implementation of both of these dietary strategies by using a caloric-restricted ketogenic diet against brain cancer (Seyfried TN et al 2008).

Antidepressants and brain tumors

People with brain tumors should be selective about antidepressants. There is a chemical made in the brain called glial cell-line derived neurotrophic factor (GDNF). It typically aids the survival of neurons after injury. The problem is that it also helps brain tumor cells survive, and, in particular, gliomas.

It also helps tumor cells migrate and invade surrounding brain tissue (Lu DY et al 2010, Song H et al 2006, Wan G et al 2010). Many antidepressants increase GDNF and thus may help tumor cells survive treatment.

A 2007 paper reported that amitriptyline, a tricyclic antidepressant, did so (Hisaoka K et al 2007). Serotonin itself increases GDNF (Tsuchioka M et al 2008). Antidepressants classified as selective serotonin reuptake inhibitors (SSRIs) which increase serotonin levels in the brain, may therefore increase GDNF, increasing tumor survival and helping it spread further into the brain.

While SSRIs might pose a problem, certain tricyclic antidepressants may be useful in treating brain tumors. A 2010 paper reported the effects of several tricyclic antidepressants on the cellular respiration rates of malignant glioma cells. Lowered cellular respiration rates are an indirect measure of increased apoptosis.

Clomipramine (Anafranil®) was the most potent inhibitor of cellular respiration in glioma cells. Of even more interest, combining clomipramine with the steroid drug dexamethasone had a synergistic effect, increasing cell death rates even further (Higgins SC et al 2010). This research is still in its early stages.

In the future, though, doctors may prescribe specific antidepressants during brain cancer treatments with the intention of increasing tumor cell death. Steroids are a potential problem in patients with brain cancer. Almost all patients who undergo surgery or radiation treatment will be prescribed some form of steroid medication, like prednisone, as part of their treatment.

These drugs are needed to reduce brain swelling. The problem is that these drugs may inhibit apoptosis in glioma cells, preventing cancer cell death. A 2000 paper concluded,,

“Since glucocorticoids are often used in the treatment of gliomas to relieve cerebral edema, the inhibition of apoptosis by these compounds could potentially interfere with the efficacy of chemotherapeutic drugs” (Gorman AM et al 2000).

Steroids also block the chemotherapy drug camptothecin from killing glioma cells (Qian YH et al 2009). Patients should be cautious in using these drugs. Concomitant use of curcumin and boswellia may act to reduce inflammation, reducing the necessity for steroids.

Summary

Given the inadequacy of standard medical treatment in controlling high-grade malignant brain tumors, this approach of co-treating brain tumors with brain tumor-specific diet and nutritional supplementation, in addition to the medical oncology standard of care, is an option that offers hope to those afflicted with brain tumors.

Because of the synergistic effects between various anti-cancer nutrients and phytochemicals, Life Extension Foundation recommends use of a wide variety of these substances rather than attempting to rely on large doses of single nutrients to fight cancer.

Life Extension Recommendations

Brain Tumor Safety Caveats

Inositol

  • An enzyme that requires inositol to function is a key regulator of angiogenesis and invasion in malignant glioma (Auf G et al 2010). It should be avoided.

Serotonin

  • 5-HTP and the selective serotonin reuptake inhibitor antidepressants should be avoided.

Steroids

  • Patients should be cautious in using these drugs.

Online Resources

The Oncology Association of Naturopathic Physicians. Lists of naturopathic physicians who specialize in naturopathic oncology as well as naturopathic physicians who have been board certified in naturopathic oncology are found on this website.

American Brain Tumor Association Thank you for taking the time to read Brain Tumor Protocol Your success is our passion. If you have any questions or contributions, please contact us via email or phone-call.

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