Nutritional Therapy and Supplements
Dietary-Derived Targeted Therapy
Biologically active extracts (from fruits, vegetables, and herbs) that specifically target cancer cell growth provide complementary therapy options to pancreatic cancer patients who do not have time to wait for large-scale clinical trials to validate the usefulness of these dietary agents, either alone or in combination with conventional treatments.
Dietary-derived extracts with proven specific bioactivity that have been used clinically to treat pancreatic cancer patients include curcumin, genistein, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), alpha-lipoic acid, perillyl alcohol (Belanger 1998), and antioxidants. These dietary agents contain several biologically active constituents, in addition to vitamins, minerals, and micronutrients that exert multiple anti-cancer effects on pancreatic cancer cells and tumors, and specifically target pathways at the molecular, cellular, and physiological level, resulting in suppression of cancer growth, invasion, and metastasis (Johnson 2011)
Other dietary-derived extracts that suppress pancreatic cancer cell/tumor growth, progression, and spread (in vivo and in vitro) include green tea (EGCG), resveratrol, pomegranate, pterostilbene, and limonene. These nutritional supplements prevent pancreatic progression and cause tumor cell death by affecting multiple intracellular signaling molecules in pancreatic cancer development such as p53, K-ras, NF-kB, EGFR, STATs, COX-2, and TNF-α (Shanmugan 2011).
Studies suggest that a diet containing multiple dietary-derived bioactive agents is preferable and much more effective over single agents for the prevention and/or treatment of pancreatic cancer. For example, curcumin combined with omega-3 fatty acids, and isoflavones together with curcumin, provided synergistic inhibitory activities against pancreatic cancer (Swamy 2008). Combinatorial treatment with multiple dietary-derived bioactive agents exerts superior anti-tumor effects than either agent alone, partly due to the specific inhibition of multiple signaling pathways (in this case Notch-1 and NF-kB) (Wang 2006).
Curcumin. Curcumin is extracted from the Indian spice turmeric (Curcuma longa L.). It is one of the most important bioactive anticancer compounds and has been extensively researched for preventing and treating pancreatic cancer.
Curcumin inhibits several signaling pathways in pancreatic cancer cells at multiple levels, such as transcription factors (NF-kB, Notch-1, STAT3, and AP-1) (Lev-Ari 2006; Wang 2006), enzymes (COX-2, MMPs, and 5-LOX), cell cycle growth factors (cyclin D1), proliferation (Ras, EGFR, HER2, and Akt), survival pathways (β-catenin and adhesion molecules), and TNF, prostaglandin E2, and interleukin-8 (Li 2004; Shehzad 2010), ultimately leading to increased pancreatic cancer cell death (Dhillon 2008). In pancreatic cancer studies, curcumin has been used as a bioactive agent in lab, animal, and phase I, II, and III human trials.
Clinical Trials with Curcumin. Phase II clinical trials of curcumin determined that curcumin can be safely taken by cancer patients at oral doses up to 8 grams (g) per day (Johnson 2011). However, results of the most recent clinical trial using curcumin to treat advanced pancreatic cancer patients revealed that the curcumin dose of 8g/d was difficult to tolerate (due to abdominal fullness/discomfort) and the researchers recommended that other formulations of curcumin (with improved systemic bioavailability and therapeutic efficacy) be evaluated for future trials (Epelbaum 2010).
A phase I/II study of 21 gemcitabine-resistant patients with pancreatic cancer receiving 8 g daily of oral curcumin in combination with gemcitabine-based chemotherapy found the combination therapy to be safe, well-tolerated, and feasible. Median survival time after initiation of curcumin was 161 days (109-223 days) and 1-year survival rate was 19% (4.4-41.4%) (Kanai 2011).
Curcumin continues to exhibit promise as an anti-cancer agent, as it is remarkably bioactive but also non-toxic even at high doses. Pilot phase I clinical trials have shown curcumin to be safe even when consumed at a daily dose of 12g for 3 months (Goel 2008). At the 2011 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium, preclinical evidence was presented regarding the efficacy of curcumin (Strimpakos 2011 Abstract #222). Please note that the forms of curcumin used in these clinical studies were not the superior absorbing forms of curcumin that are now available over-the-counter. It is very important that the curcumin you take comes from a highly bioavailable form of tumeric extract.
Genistein. Genistein, an isoflavone extracted from soybeans, has been widely studied in pancreatic cancer. Genistein inhibits pancreatic cancer progression at the genetic, cellular, and physiological level.
At the genetic level, genistein prevents pancreatic cancer growth via targeted inhibition of Ras (Berner 2010), NFkB (Jotooru 2010), EGFR (McIntyre 1998), HER2 (Wang 2010), STAT3 (Huang 2011) and activation of p53 (Lian 1999). At the cellular level, genistein regulates glucose metabolism (Boros 2001). At the physiological level, genistein exerts potent antiangiogenic and anti-metastatic activities by impairing the activation of hypoxia inducible factor-1 (HIF-1) and suppressing VEGF (in vivo) (Buchler 2004). Intratumoral hypoxia is known to lead to increased tumor aggressiveness and distant metastasis and genistein prevents this occurrence.
Clinical Trials with Genistein. A phase II clinical trial on the use of genistein in combination with gemcitabine and erlotinib to treat patients with advanced or metastatic pancreatic cancer was performed. Genistein in the form of soy isoflavones at a dose of 531 mg twice daily was taken by pancreatic cancer patients. The trial showed that the addition of soy isoflavones to gemcitabine and erlotinib did not increase the survival of advanced pancreatic cancer patients (El-Rayes 2011). The researchers speculate that the benefit of adding soy isoflavones may be limited to patients whose tumors overexpress NF-kB, thus emphasizing the urgent need for individualized treatment plans.
As of September 2011, there is a phase I/II clinical trial investigating the effect of a crystalline form of genistein (AXP107-11) alone, and in combination with gemcitabine, in patients with advanced or metastatic cancer of the pancreas (www.clinicaltrials.gov).
The suggested dose of genistein is approximately 500 mg daily, which requires the swallowing of about five soy isoflavone concentrated capsules (3,500 mg soy extract daily flavones). This should be taken in two daily doses, each consisting of about 1,750 mg of soy isoflavone extract (to provide a total daily intake of 3,500 mg) (Miltyk 2003; Takimoto 2003).
Fish Oil. Weight loss in advanced pancreatic cancer patients (catabolic wasting or cachexia) is refractory to conventional nutritional support. However, it is well-established that supplementation with fish oil, rich in omega-3 fatty acids (EPA and DHA), reverses tumor-related weight loss (cachexia). Eicosapentaenoic acid (EPA) modulates the inflammatory response that contributes to weight loss in cancer and thus reverses cancer cachexia (Arshad 2011).
Omega-3 fatty acids, EPA and DHA, prevent pancreatic cancer progression and cause pancreatic tumor cell death by activating p53 (Wendel 2009) and blocking the activity of Ras (Strouch 2011), EGFR (Rogers 2010), COX-2 and 5-LOX (Swamy 2008), STAT3 (Hering 2007), and NF-kB (Ross 2003).
In a phase I study of five pancreatic cancer cachexia patients, a mean dose of approximately 18 grams per day (doses ranged from 9 to 27 grams per day) of a high-purity preparation of EPA was tolerated (Barber 2001).
Fish oil supplements providing at least 2,400 mg of EPA and 1,800 mg of DHA daily have been recommended (Anderson 1998a). To reduce cachexia, an estimated 2 to 12 grams per day of EPA is needed (Persson 2005).
Clinical Studies with Fish Oil. Many clinical studies in pancreatic cancer patients show that fish oil, omega-3 fatty acids, and/or EPA supplementation reverses weight loss caused by cancer (cachexia).
In an international, multicenter, randomized trial, a nutrition prescription of a protein and energy dense, oral nutritional supplement +/- omega-3 fatty acids taken by 200 untreated patients with unresectable pancreatic cancer over an 8-week period significantly improved weight (1.7 kg), protein (25.4 g) and energy (501kcal) intake (Bauer 2005).
Consumption of a protein- and energy-dense nutritional supplement containing omega-3 fatty acids (EPA) improved body weight, lean body mass, and quality of life in patients undergoing chemotherapy (Chen da 2005).
In a prospective, randomized, double-blinded clinical trial on 44 cancer patients undergoing major abdominal tumor surgery, daily fish oil and soybean oil supplementation (0.2 and 0.8 g/kg body weight, respectively) prevented weight loss and enabled a faster recovery (Heller 2004).
In a study of 24 home-living cachectic patients with advanced pancreatic cancer, the administration of an energy and protein dense oral supplement enriched with EPA, over an 8-week period, was associated with an increase in physical activity and improved quality of life (Moses 2004).
EPA enriched protein supplements improved physical activity levels and increased total energy expenditure in advanced pancreatic cancer patients, thereby increasing their quality of life (Klek 2005).
Vitamin D. Pancreatic cancer patients have a high prevalence of vitamin D deficiency indicating the need for appropriate supplementation (Fisher 2009). Low serum vitamin D levels, as defined by serum vitamin D levels of <32 ng/mL using Labcorp testing method for 25-hydroxyvitamin D, in pancreatic cancer patients take longer to respond to oral vitamin D supplementation compared to healthy individuals (Vashi 2010), suggesting that more aggressive supplementation may be required to obtain Life Extension’s optimal level of 50 – 80 ng/mL.
Vitamin D3 has multiple protective effects against pancreatic cancer including anti-angiogenic, anti-metastatic, anti-inflammatory, and immunomodulatory effects (Hung Pham 2011; Bulathsinghala 2010).
Perillyl Alcohol. Perillyl alcohol is a naturally derived monoterpene with activity against pancreatic cancers that have a K-ras mutation. It prevents the mutated ras proteins from stimulating pancreatic cancer growth (Stayrook 1998). Perillyl alcohol treatment causes complete pancreatic tumor regression in animal experiments (Burke 2002). Clinically achievable concentrations of perillyl alcohol combined with a virally delivered therapeutic cytokine (adenovirus-mediated mda-7/IL-24 gene therapy (Ad.mda-7)) effectively eliminated human pancreatic cancer cells grown in mice and increased their survival (Lebedeva 2008).
Clinical Studies with Perillyl Alcohol. A pilot study of perillyl alcohol in 8 pancreatic cancer patients showed that perillyl alcohol was well tolerated. Survival time was longer in patients who received full perillyl alcohol treatment (288 +/- 32 days) compared to those who did not (204 +/- 96 days), but this result did not achieve statistical significance. There was a trend toward greater apoptosis in tumors versus normal pancreatic tissue of patients receiving perillyl alcohol (Matos 2008).
Twelve clinical trials have investigated the use of perillyl alcohol in various types of cancer treatments. A 2050-mg dose given four times daily was found to be easily tolerated (Morgan-Meadows 2003). The minimum required antitumor dose is 1.3 grams per day (Boik 2001).
Antioxidants. Individual variations in the capacity to defend against oxidative stress and to repair oxidative DNA damage influence pancreatic cancer risk, and some of these genetic effects are modified by dietary antioxidants (Zhang 2011). Moreover, antioxidant levels are reduced in pancreatic tumors compared to healthy pancreatic tissue, resulting in increases in reactive oxygen species (ROS) that are capable of stimulating cancer growth (Garcea 2005; Vaquero 2004).
Vitamins A, C, and E. An overview of 14 randomized trials (with a total of 170,525 patients) showed significant effects of supplementation with beta-carotene, vitamins A, C, E, and selenium (alone or in combination) versus placebo on pancreatic cancer incidence (Bjelakovic 2004).
Retinoic acid slows pancreatic tumor progression and reduces motility of pancreatic stellate cells (PSCs) (Froeling 2011). A study of 23 pancreatic cancer patients tested retinol palmitate (vitamin A) and beta-interferon with chemotherapy. Eight patients responded and eight patients had stable disease. For all patients, median time to disease progression and survival time were 6.1 months and 11 months, respectively. Toxicity was high, but patients who had responses and disease stabilization had prolonged symptom relief (Recchia 1998).
Vitamins A, C, and E, as well as selenium, increase antioxidants needed to reduce free-radical damage in the body (Woutersen 1999). A double-blind, placebo-controlled, randomized clinical trial involving 36 cancer patients undergoing surgery for pancreatic cancer evaluated the impact of an oral nutritional supplement (enriched with antioxidants, glutamine and green tea extract) on postoperative oxidative stress. Patients received the antioxidant-enriched supplement twice the day before surgery and once 3 hours before surgery. The nutritional supplement improved total antioxidant capacity (plasma levels of vitamin C, vitamin E, selenium, and zinc) shortly after surgery and increased plasma vitamin C levels (Braga 2011).
Recent data support the use of pharmacological doses of ascorbate in adjunctive treatment (e.g., with gemcitabine) for pancreatic cancer (Espey 2011). Ascorbate induces autophagy in pancreatic cancer cells (Cullen 2010).
Melatonin. Recently, it was discovered that melatonin reduces pancreatic tumor cell viability by altering mitochondrial physiology (Gonzalez 2011). Furthermore, advanced pancreatic cancer patients have abnormal circadian fluctuations in melatonin levels (Muc-Wierzgon 2003), which should be corrected by melatonin supplementation because even low (physiologically normal) concentrations of melatonin have a pro-apoptotic effect on pancreatic cancer cells resulting in tumor cell death (Leja-Szpak 2010).
Clinical Studies with Melatonin. A clinical-study of melatonin plus immunotherapy in the treatment of fifty advanced pancreatic adenocarcinoma patients resulted in a significantly higher 1 year survival rate in the melatonin treated group than other groups tested (3/12 vs 1/38), suggesting that melatonin immunotherapy is a promising treatment of advanced pancreatic cancer (Lissoni 1994).
A phase II study of melatonin plus tamoxifen in metastatic solid tumor patients was performed. Included in the study were five pancreatic cancer patients, for whom no other standard therapy was available. Melatonin (20 mg at night) and tamoxifen (20 mg at noon) were given orally every day. Results indicated that the combination of melatonin plus tamoxifen may have some benefit in untreatable metastatic solid tumor patients (Lissoni 1996).
In another clinical study in which melatonin plus low-dose interleukin-2 (IL-2) was used to treat pancreatic cancer patients with a life expectancy of less than 6 months, a complete response was achieved in one pancreatic cancer patient, and a partial response in three others. Immunotherapy with melatonin and IL-2 was a well-tolerated and effective therapy for almost all advanced cancer patients with solid tumors, including those who did not respond to IL-2 alone or to chemotherapy (Lissoni 1995).
Investigational Nutritional Supplements
Pancreatic cancer treatment advances, whether conventional or alternative, have to be proven first in the laboratory before applying them to patients. However, epidemiological or population-based studies also provide evidence of the benefits of specific dietary interventions.
Epidemiological studies as well as laboratory and animal experiments suggest the following nutritional components may have a role in pancreatic cancer treatment.
Limonene is extracted from citrus fruits. It has been shown to reduce growth of pancreatic cancer cells by 50% (Karlson 1996; Crowell 1996). Limonene is well tolerated in cancer patients at doses that may have clinical activity (Chow 2002). One partial response in a breast cancer patient at a dose of 8 g/m2/day (8 grams taken twice daily) was maintained for 11 months. Three patients with colorectal cancer showed disease stabilization for longer than 6 months on d-limonene at 0.5 or 1 gram twice daily (Vigushin 1998). The tentative dose recommendation for limonene is 7.3 to 14.4 grams per day (Boik 2001; Vigushin 1998). Daily consumption of d-limonene from food sources is estimated to be 16.2 mg/person/day (0.27 mg/kg body weight/day) (Sun 2007).
Selenium levels were found to be reduced in 57% of pancreatic cancer patients who underwent surgery to remove the upper portion of their intestines. Many long-term survivors (>6 months) of pancreatic surgery have frank selenium deficiencies. Thus, it is recommended that micronutrient status should be regularly checked in these patients and treated where necessary (Armstrong 2007).
High-selenium yeast was shown to reduce cancer risk in an intervention trial (Clark 1996). Patients with previous skin cancer were supplemented with 200 mcg of selenium or placebo daily for an average of 4.5 years. At a 6-year follow up, it was found that those in the selenium group had a significant reduction in total cancer mortality, total cancer incidence, and incidences of lung, colorectal, and prostate cancers. Additional studies utilizing selenium supplementation have shown benefit in prostate and lung cancer (Combs 1997; Meyer 2005).
Selenium and beta-carotene were found to restrain the growth of pancreatic tumors caused by carcinogen exposure in mice (Appel 1996). In another preclinical study, a diet high in selenium reduced the number of carcinogen-induced pancreatic cancers significantly (Kise 1990).
Vitamin K. Population studies as well as animal and laboratory data suggest a role for vitamin K in cancer prevention and treatment (Nimptsch 2008; Osada 2001). In one laboratory study, vitamin K combined with the drug sorafenib strongly inhibited growth and induced apoptosis in pancreatic cancer cells (Wei 2010)
Vitamin B6. Animal and epidemiological studies have linked anti-tumorigenic and anti-inflammatory effects to dietary vitamin B6 (Larsson 2010). In a pooled analysis of data from 4 cohorts including 208 pancreatic cancer cases and 623 controls, subjects in the highest quartile (one-fourth) for plasma vitamin B6 concentrations were 20% less likely to have pancreatic cancer than those in the lowest quartile (Schernhammer 2007). Among male smokers in another study, those in the lowest one-third distribution of concentrations of the active form of vitamin B6 – pyridoxal-5’-phosphate – were about twice as likely to develop pancreatic cancer compared to those in the highest one-third (Stolzenberg-Solomon 1999).
Green Tea. In a large population-based case-control study conducted in China it was found that drinking green tea lowers the risk of pancreatic cancer (Ji 1997).
Epigallocatechin gallate (EGCG) is the main bioactive polyphenolic constituent in green tea. Animal studies show that EGCG inhibits pancreatic tumor growth, angiogenesis, invasion, and metastasis (Shankar 2007). Furthermore, EGCG, suppressed the development of pancreatic tumors in Syrian hamsters (Majima 1998; Hiura 1997).
Increasing evidence suggests an association of chronic inflammation in cancer development in which IL-1 plays a crucial role. Recent experimental studies show that EGCG downregulates IL-1RI expression and suppresses IL-1-induced tumorigenic factors in human pancreatic cancer cells resulting in tumor cell death (Hoffmann 2011).
EGCG’s anticancer activities in human pancreatic carcinoma cells are partly via the inhibition of insulin-like growth factor-I receptor (IGF-1R) (Vu 2010). EGCG (and the buckwheat flavonoid rutin) decrease induced glucotoxicity in pancreatic beta cells, preserving insulin signaling (Cai 2009). Furthermore, EGCG improves pancreatic injury in animal models of acute pancreatitis (Babu 2009). Green tea polyphenols (GTPs) prevent pancreatic fibrosis by inhibiting activated pancreatic stellate cells (PSCs). PSCs play a central role in the pathogenesis of pancreatic fibrogenesis and inflammation. EGCG inhibits PSC activation through antioxidant mechanisms (Asaumi H 2006) and prevents migration of PSCs (Masamune 2005). EGCG also decreases the expression of the K-ras gene (Lyn-Cook 1999).
Clinical evidence shows that green tea supplementation is safe and protective against some types of cancer (Stingl 2011).
Zinc is a trace element essential for normal cell growth. Zinc deficiency may have role in cancer promotion (Prasad 2009).
L-carnitine has been shown to augment the cytotoxicity of cisplatin and is involved in the mitochondrial transport of acetyl groups (Peluso 2000; Pisano 2010).
Acetyl-L-carnitine may indirectly influencethe stability of the p53 tumor suppressor gene. The activity of this gene enhances the cytotoxicity of cisplatin chemotherapy drugs. Based on this information, researchers investigated the effects of acetyl-L- carnitine in combination with cisplatin on cancer cell lines. The results revealed a significant antimetastatic activity of acetyl-L-carnitine and enhancement of the antitumor potential of platinum chemotherapy (Pisano 2010).
L-carnitine deficiency is proposed to be a cause of cancer-related weight loss (cachexia). In a randomized controlled trial, advanced pancreatic cancer patients receiving 4 grams of L-carnitine daily for 12 weeks gained weight (BMI increased 3.4%), while the control group continued to lose weight (BMI decreased 1.5%). Patients supplemented with L-carnitine also experienced improved nutritional status, increased overall survival and reported better quality of life (Kraft 2012).
Complementary Alternative Therapies
PSK (Polysaccharide K). PSK is a protein-bound polysaccharide derived from the mycelium of the mushroom Coriolus versicolor (Tsukagoshi 1984). In Japan, PSK is used as a non-specific biological response modifier to enhance the immune system in cancer patients (Koda 2003).
Two patients who had unresectable pancreatic cancer were treated with combined chemotherapy using cisplatin, PSK, and UFT (uracil-tegafur). During therapy, a partial response was observed, with a remarkable decrease in tumor size and no significant side effects. From the results of these two cases, this combination chemotherapy was considered to be one of the most effective therapies available for pancreatic cancer (Sohma 1987). PSK has been used as adjuvant immunotherapy for cancer at a dose of 3 grams daily (Ito 2004).
Recent studies showed that PSK has strong antitumor effects via stimulation of both innate and adaptive immune pathways (Lu 2011a). Furthermore, PSK activates human natural killer (NK) cells and significantly potentiates the anti-tumor effect of anti-HER2 monoclonal antibody therapy (in mice). Therefore, concurrent treatment of PSK and trastuzumab may be a novel way to augment the anti-tumor effect of trastuzumab (Lu 2011b).
PSK suppresses tumor cell invasiveness by down-regulating several invasion-related factors (Zhang 2000). PSK enhances pancreatic cancer cell death induced by Taxotere® (docetaxel) by inhibiting docetaxel-induced NF-kB activation (Zhang 2003).
Ukrain (NSC-631570). Ukrain is a semisynthetic derivative of the Chelidonium majus L. alkaloid chelidonine shown to prolong survival of pancreatic cancer patients.
In a phase II trial of advanced pancreatic cancer patients, Ukrain either alone or together with Gemzar® (gemcitabine) doubled median survival times (Gansauge 2002).
In another clinical study, Ukrain with vitamin C treatment prolonged the survival and improved the quality of life of patients with advanced pancreatic cancer. In this study, patients were administered IV therapy consisting of either vitamin C (5.4 g every second day, repeated 10 times) and Ukrain (10 mg every second day, repeated 10 times) (21 patients), or vitamin C (5.4 g every second day x 10) and normal saline (10 ml) (control group, 21 patients). The one-year survival was 81% versus 14% and the 2-year survival was 43% versus 5% (Ukrain vs control group). Median survival was 17.17 versus 6.97 months in the Ukrain versus control group, respectively. The longest survival in the Ukrain group was 54 months (Zemskov 2000).
Ukrain’s proapoptotic activity is based on Chelidonium majus L. alkaloids and is mediated via a mitochondrial death pathway (Habermehl 2006). Ukrain is able to control the expression of some of the key mediators of tumor progression in pancreatic carcinoma cells. It downregulates matrix metalloproteinases, suggesting that it may decrease pancreatic cancer cell invasion. It also reduces tumor cell proliferation by cell cycle inhibition, via G2/M phase arrest (Funel 2010).
Seven randomized clinical trials suggest that Ukrain has curative effects on a range of cancers, including pancreatic cancer. However, the methodological quality of most studies was poor; therefore, independent rigorous studies are urgently needed (Ernst 2005).
Alpha-Lipoic Acid / Low-Dose Naltrexone (ALA/N)
The Integrative Medical Center of New Mexico, (located in Las Cruces) previously reported the long-term survival of a male patient with pancreatic cancer metastasized to the liver, treated with intravenous alpha-lipoid acid and oral low-dose naltrexone (ALA/N) (and a healthy lifestyle program) without any toxic adverse effects. The man was alive and well 78 months after initial treatment (Berkson 2006) even though he was told by a reputable oncology center in October 2002 that there was little hope for his survival.
Clinical Studies with ALA/N
Recently three new patients with metastatic pancreatic cancer were treated with the ALA/N protocol at the same center. In 2010, it was reported that the first patient is alive and well 39 months after presenting with pancreatic adenocarcinoma with metastases to the liver. The second patient, also with pancreatic adenocarcinoma with metastases to the liver, was treated with the ALA/N protocol and after 5 months of therapy, PET scan showed no evidence of disease. The third patient, in addition to his pancreatic cancer with liver and retroperitoneal metastases, has a history of B-cell lymphoma and prostate adenocarcinoma. After 4 months of the ALA/N protocol his PET scan showed no evidence of cancer. ALA/N exerts multiple anti-cancer effects including reducing oxidative stress, stabilizing NFkB, stimulating apoptosis, inhibiting tumor cell proliferation and modulating an immune response (Berkson 2009)
Berkson and colleagues (2009) believe that the results from their ALA/N integrative protocol warrant clinical trials, stating that “given its lack of toxicity at levels reported it may have the possibility of extending the life of a patient who would be customarily considered to be terminal.”
The ALA-LDN protocol comprises alpha-lipoic acid (ALA) (300 to 600 mg intravenously twice weekly), low-dose naltrexone (Vivitrol™) (3 to 4.5 mg at bedtime), and orally, ALA (300 mg twice daily), selenium (200 micrograms twice daily), silymarin (300 mg four times daily), and vitamin B complex (3 high-dose capsules daily). In addition, a strict dietary regimen, stress-reduction and exercise program, and a healthy lifestyle are essential.
Disclaimer and Safety Information
This information (and any accompanying material) is not intended to replace the attention or advice of a physician or other qualified health care professional. Anyone who wishes to embark on any dietary, drug, exercise, or other lifestyle change intended to prevent or treat a specific disease or condition should first consult with and seek clearance from a physician or other qualified health care professional. Pregnant women in particular should seek the advice of a physician before using any protocol listed on this website. The protocols described on this website are for adults only, unless otherwise specified. Product labels may contain important safety information and the most recent product information provided by the product manufacturers should be carefully reviewed prior to use to verify the dose, administration, and contraindications. National, state, and local laws may vary regarding the use and application of many of the treatments discussed. The reader assumes the risk of any injuries. The authors and publishers, their affiliates and assigns are not liable for any injury and/or damage to persons arising from this protocol and expressly disclaim responsibility for any adverse effects resulting from the use of the information contained herein.
The protocols raise many issues that are subject to change as new data emerge. None of our suggested protocol regimens can guarantee health benefits. The publisher has not performed independent verification of the data contained herein, and expressly disclaim responsibility for any error in literature.