By Stephen Daniells, 10-Feb-2010

Related topics: Nutritional lipids and oils, Cancer risk reduction, Women’s health

Supplements of the omega-3 fatty acid docosahexaenoic acid (DHA) may improve outcomes for breast cancer patients undergoing chemotherapy, says a new study from France.

A daily dose of 1.8 grams of DHA also produced no adverse effects, according to a new study published in the British Journal of Cancer.

“Our data show for the first time that a dietary intervention targeted on DHA is a feasible approach that has potential to substantially increase survival in metastatic breast cancer patients treated with chemotherapy,” wrote the researchers, led by Dr Philippe Bougnoux from the French Institut National de la Santé Et de la Recherche Médicale (INSERM) U921 in Tours.

Being a phase II clinical trial, the research represents an “incentive to set up a prospective-controlled randomised trial aimed at identifying the place of dietary DHA in breast cancer treatments”, added the researchers.

Every year about 1.3 million women are diagnosed with breast cancer around the world, with just fewer than half a million deaths associated with the disease, according to the American Cancer Society (ACS).

While the incidence of the disease has increased by about 30 per cent over the last 25 years in the west, death rates have declined dur to improved detection and tratments, said the ACS.

The new study, if supported by additional research, suggests that DHA may help improve survival by sensitising tumours to chemotherapy, said Dr Bougnoux and his co-workers.

Study details

The Tours-based researchers recruited 25 women with breast cancer to participate in their open-label single-arm phase II study. As part of their anthracycline-based chemotherapy (FEC) regimen women were given additional DHA (1.8 grams per day, DHA-enriched triglyceride oil of algal origin, supplied by Martek Biosciences) for between 2 and 96 months.

After an average of 31 months, Dr Bougnoux and his co-workers found that the overall survival of women was 22 months, and reached 34 months in women with the highest DHA levels in their blood.

“Although the median time to progression (6 months) and overall survival (22 months) in our study were within the frame of published data, it should be stressed that our patient population had a particularly poor prognosis, as 68 per cent had liver metastases in addition to other sites of metastases,” stated the researchers. “The median overall survival of patients having liver metastases was reported to be 14 months.”

Importantly the DHA supplements during chemotherapy were not associated with any adverse side effects, they added.

Source: British Journal of Cancer
Volume 101, Pages 1978–1985, doi:10.1038/sj.bjc.6605441
“Improving outcome of chemotherapy of metastatic breast cancer by docosahexaenoic acid: a phase II trial”
Authors: P. Bougnoux, N. Hajjaji, M.N. Ferrasson, B. Giraudeau, C. Couet, O. Le Floch

ScienceDaily (Dec. 9, 2009) — A new study has found that the amount of vitamin D in patients being treated for diffuse large B-cell lymphoma was strongly associated with cancer progression and overall survival. The results will be presented at the annual meeting of the American Society of Hematology in New Orleans.

“These are some of the strongest findings yet between vitamin D and cancer outcome,” says the study’s lead investigator, Matthew Drake, M.D., Ph.D., an endocrinologist at Mayo Clinic in Rochester. “While these findings are very provocative, they are preliminary and need to be validated in other studies. However, they raise the issue of whether vitamin D supplementation might aid in treatment for this malignancy, and thus should stimulate much more research.”

The researchers’ study of 374 newly diagnosed diffuse large B-cell lymphoma patients found that 50 percent had deficient vitamin D levels based on the commonly used clinical value of total serum 25(OH)D less than 25 ng/mL. Patients with deficient vitamin D levels had a 1.5-fold greater risk of disease progression and a twofold greater risk of dying, compared to patients with optimal vitamin D levels after accounting for other patient factors associated with worse outcomes.

The study was conducted by a team of researchers from Mayo Clinic and the University of Iowa. These researchers participate in the University of Iowa/Mayo Clinic Lymphoma Specialized Program of Research Excellence (SPORE), which is funded by the National Cancer Institute. The 374 patients were enrolled in an epidemiologic study designed to identify predictors of outcomes in lymphoma. Since this was not a clinical trial, patient management and treatments were not assigned, but rather followed standard of care for clinical practice.

The findings support the growing association between vitamin D and cancer risk and outcomes, and suggest that vitamin D supplements might help even those patients already diagnosed with some forms of cancer, says Dr. Drake. “The exact roles that vitamin D might play in the initiation or progression of cancer is unknown, but we do know that the vitamin plays a role in regulation of cell growth and death, among other processes important in limiting cancer,” he says.

The findings also reinforce research in other fields that suggest vitamin D is important to general health, Dr. Drake says. “It is fairly easy to maintain vitamin D levels through inexpensive daily supplements or 15 minutes in the sun three times a week in the summer, so that levels can be stored inside body fat,” he says. Many physicians recommend 800-1,200 International Units (IU) daily, he adds.

Vitamin D is a steroid hormone obtained from sunlight and converted by the skin into its active form. It also can come from food (naturally or fortified as in milk) or from supplements. It is known best for its role of increasing the flow of calcium into the blood. Because of that role, vitamin D deficiency has long been known to be a major risk factor for bone loss and bone fractures, particularly in elderly people whose skin is less efficient at converting sunlight into vitamin D. But recent research has found that many people suffer from the deficiency, and investigators are actively looking at whether low vitamin D promotes poorer health in general.

Cancer researchers have discovered that vitamin D regulates a number of genes in various cancers, including prostate, colon and breast cancers. Recent studies have suggested that vitamin D deficiency may play a role in causing certain cancers as well as impacting the outcome once someone is diagnosed with cancer.

Researchers looked at vitamin D levels in lymphoma patients because of the observation, culled from U.S. mortality maps issued by the National Cancer Institute, that both incidence and mortality rates of this cancer increase the farther north a person lives in the United States, where sunlight is limited in the winter. Also, several recent reports have concluded that vitamin D deficiency is associated with poor outcomes in other cancers, including breast, colon and head and neck cancer. This is the first study to look at lymphoma outcome.

The study was funded by the National Cancer Institute and the Mayo Hematologic Malignancies Lymphoma Fund.

Hardy ML. Dietary supplement use in cancer care: help or harm. Hematol Oncol Clin N Am. 2008;22: 581-617.

Studies consistently show that most cancer patients use dietary supplements (DS) in all phases of treatment, most often without revealing use, or revealing it only partially, to oncologists. Most oncologists recommend complete avoidance of DS, reducing patients’ willingness to disclose use and thereby potentially increasing risks. Overall, physicians and patients do not share the same perceptions of possible benefits from complementary and alternative medicine (CAM) or agree on what evidence to use for CAM therapy.

Some risks cited by oncologists for CAM use are not fully supported by research. These include fears that patients using CAM may refuse or delay conventional treatment or that CAM products may be contaminated or adulterated, and risk of liver toxicity from DS. The author states that these risks are relatively small and would be best guarded against by physician-patient communication. In one study, only 8% of advanced cancer patients were receiving alternative care alone. According to the author, contaminated or adulterated DS should be substantially reduced under new rules from the Food and Drug Administration. Not all evidence of liver toxicity for herbs is equally compelling; in particular, reports involving black cohosh (Actaea racemosa syn. Cimicifuga racemosa) were insufficiently persuasive for the National Institutes of Health to halt or modify clinical trials.

Herb-drug interactions, another risk cited by oncologists, have been the subject of several reviews, but only two studies. In one, of 76 chemotherapy patients, three were using botanical DS that could interfere with the chemotherapeutic agent: St. John’s wort (SJW; Hypericum perforatum) and garlic (Allium sativum). In another, of 318 chemotherapy patients also taking herbs, 11% took DS in higher-than-recommended doses. Potential interactions were inferred for 12%, mostly with echinacea (Echinacea spp.) on the presumption that it might adversely affect immune stimulation. However, neither study confirmed any interactions. In screening tests, herbal preparations have shown the ability to up- or down-regulate activity of P450 isoenzymes, but relatively few clinical trials have verified this. One review assessed in vitro, in vivo, and human data for common herbs concluding that, in chemotherapy, interactions with black cohosh, milk thistle (Silybum marianum), saw palmetto (Serenoa repens), cranberry (Vaccinium macrocarpon), and bilberry (Vaccinium myrtillus) were not expected. Mostly preclinical research suggests that for garlic, ginkgo (Ginkgo biloba), soy (Glycine max), Asian ginseng (Panax ginseng), valerian (Valeriana officinalis), and kava (Piper methysticum), precautions should be taken. Human studies with SJW and imatinib found reduced levels and increased clearance of the drug; similar results were found for SJW and irinotecan. Induction of CYP450 enzymes is thought to be caused by hyperforin, one constituent of SJW. In no pharmacokinetic study cited was composition of the SJW extract described or independently confirmed by investigators.

Reduced blood coagulation, perhaps due to antiplatelet action or interference with warfarin, is also cited as a risk for cancer patients using DS. Evidence for either effect is mixed with mostly poor quality case reports unsupported by in vivo research.

Some herbs’ phytohormonal effects cause concern for oncologists with regards to hormone-sensitive cancers, particularly breast, ovarian, endometrial, or prostate. Research has focused on estrogenic activity in menopause. Both soy and red clover (Trifolium pratense) extracts are phytoestrogenic, with uncertain significance for estrogen receptor-positive breast cancer patients. Black cohosh, however, does not appear to be estrogenic. Activity on serotonergic neutrons in the hypothalamus may account for its effects on symptoms of menopause.

While eating antioxidant-rich foods is associated with reduced risk of many cancers, using antioxidant DS to prevent cancer is not supported by large randomized trials and has at times been found to increase risk. However, a large amount of preclinical data and some human trials support use of some antioxidants, e.g., high-dose vitamin C for possible tumor response; and vitamins C, E, and coenzyme Q10 to reduce chemotherapy-related toxicity. Some evidence for harm exists for vitamin E use in head and neck cancers.

                                                                * * *

While most perceived risks remain theoretical or even unlikely, benefits are found for cancer patients from many CAM products in overall quality of life and reduced side effects of conventional treatment. The author omits discussion of lectin compounds from mistletoe (Viscum album), and a polysaccharide extract from shiitake mushroom (Lentinus edodes), because both are delivered parenterally or intravenously, and therefore are not DS by US standards; and omits whole-herb cannabis (Cannabis sativa) extracts and isolated compounds because of “legal ambiguity and challenges with standardization.”

Among immunomodulators, mushrooms and mushroom-derived polysaccharides improved quality of life, modified tumor response, and boosted immune response in several cancer models and some clinical trials, mostly in patients with solid tumors. A proprietary extract of turkey tail mushroom (Trametes versicolor syn. Coriolus versicolor), PSK® (JHS Natural Products; Eugene, Oregon), showed those benefits and lower relative risk of regional metastases, in trials of over 1200 subjects with colorectal cancer and over 8000 with gastric cancer. Another turkey tail extract, together with danshen (Salvia miltiorrhiza), improved immunological parameters in nasopharyngeal cancer patients having radiation therapy and in breast cancer patients. A polysaccharide extract of a proprietary hybrid mushroom identified as Basidiomycotina (probably Agaricus blazei), has shown beneficial immune effects in clinical trials, and a highly significant statistical increase in survival in some advanced liver cancer patients. An A. blazei extract given to gynecological cancer patients increased natural killer cell activity and decreased chemotherapy side effects from carboplatin, etoposide, or taxol. Other promising immunomodulators include a proprietary fermented wheat (Triticum spp.) germ extract standardized to methoxy-substituted benzoquinones (Avé® or Avemar®; American BioSciences; Blauvelt, New York), and probiotics. Unexpected and still unexplained deaths in a recent trial of probiotics in patients with severe pancreatitis mandate caution.

Stomatitis or mucositis, a common side effect of cancer therapy, reduces quality of life and caloric intake. Simple natural interventions, such as ice (plain or flavored), honey, and topical vitamin E oil, reduce stomatitis. There is strong evidence, in several cancers and with a variety of chemotherapeutic agents, for glutamine as an oral rinse that is then swallowed; however, results with 5-fluorouracil (5-FU) chemotherapy were generally negative. Zinc supplementation, a proprietary homeopathic remedy (Traumeel®; Heel, Inc.; Albuquerque, New Mexico) containing arnica (Arnica montana), and proteolytic enzymes have all shown benefit. Aloe (Aloe vera) and chamomile (Matricaria recutita) rinses have had mixed results. Chamomile fared better in uncontrolled cases with heterogenous chemotherapy and radiation than in a controlled study with 5-FU. Stomatitis is often associated with disruption of gut mucosa leading to diarrhea or leaky gut syndrome. Glutamine benefited 5-FU-induced intestinal toxicity and diarrhea associated with irinotecan in some studies, but not diarrhea from doxifluridine or neo-adjuvant chemotherapy or radiation in others. Even when no benefit was found, there was no interference with chemotherapy. Probiotics decreased diarrhea when given concurrently with 5-FU chemotherapy or radiation; again, caution is currently warranted. Both glutamine and vitamin E have shown promise in alleviating chemotherapy-induced neuropathies, caused especially by platinum-based drugs and taxanes. Ginger (Zingiber officinale), in doses as low as 1 g/d powdered root, reduces chemotherapy-induced nausea, with no serious adverse effects, and fewer side effects than metoclopramide.

Radiation therapy damages skin contributing to morbidity. So far, few herbal agents have shown benefit. Aloe is often used for radiation-induced burns, but trials have not confirmed a strong benefit. It has delayed onset of damage briefly. A proprietary chamomile cream, compared to almond (Prunus dulcis) oil, delayed onset of dermatitis and reduced damage, though the differences were not statistically significant. Those using a homeopathic calendula (Calendula officinalis) cream compared with trolamine during radiation had significantly less dermatitis and were more satisfied with the calendula cream despite its being more difficult to use.

Reviews and meta-analyses confirm the usefulness of omega-3 fatty acids in preventing cancer-related cachexia, but relatively high doses are required for efficacy: 7.5 g/d fish oil or eicosapentaenoic acid (EPA). Combining fish oil with celecoxib gave significantly more improvement in appetite, fatigue, body weight, and muscle strength than fish oil alone in a small group of patients with advanced lung cancer.

Edema after conventional cancer treatments can be a serious issue and difficult to treat. One randomized trial with selenium selenite reduced upper extremity edema and improved function of breast cancer patients, while an uncontrolled trial showed its benefit for head and neck radiotherapy. Several small studies with flavonoid-rich preparations have shown benefit, including one using a proprietary ginkgo formula.

DS studied for cancer-related fatigue have generally been ineffective, but supplementation with up to 3000 mg/d carnitine decreased fatigue and improved quality of life in carnitine-deficient patients during chemotherapy.

Black cohosh – as discussed earlier, effective against symptoms of menopause but not estrogenic – has been suggested for vasomotor symptoms in cancer therapy, especially in younger women. Not all trials have shown benefits in women with breast cancer, but some have, without serious adverse effects. And, far from increasing breast cancer risk, two studies found a possible protective effect of black cohosh extract (BCE). In a case-controlled study of 949 menopausal breast cancer patients and 1524 menopausal controls, women who took BCE had 50% less risk of developing breast cancer. In a retrospective cohort study comparing 1102 breast cancer survivors who took BCE with a small group who did not, those who used BCE had longer disease-free intervals.

While DS are inappropriate as primary cancer treatments, some show promise in pre-malignant lesions, early cancers usually treated with watchful waiting, and specific treatment-resistant cancers. Subjects with oral leukoplakia received 3 g tea (Camellia sinensis) or placebo. After six months, the treatment group had smaller lesions and fewer micronucleated exfoliated cells. High-grade intraepithelial neoplasia of the prostate (HG-PIN) has responded to oral administration of a green tea extract. Pomegranate (Punica granatum) juice (POM Wonderful®; POM Wonderful, Inc.; Los Angeles, California), given to men with rising prostate-specific antigen (PSA) after surgery or radiation, increased mean PSA-doubling time from 15 to 54 months. Another DS with soy, lycopene, silymarin, and antioxidants increased PSA-doubling time from 445 to 1,150 days. Some tumor response was seen in a trial of 10 mg/d lycopene (Lycored®; LycoRed Natural Product Industries; Beer Sheva, Israel) supplementation, for three months, in men with hormone-resistant or refractory prostate cancer (HRPC). Most were able to reduce the amount of analgesics used. Lycopene with orchiectomy improved outcomes of men with metastatic HRPC. However, given to HRPC patients as tomato (Lycopersicon esculentum) paste or juice, it showed no effect.

Oncologists are urged to become familiar with literature on DS in cancer and to accept that the majority of their patients will use DS, with or without their knowledge or approval. Being able to discuss well-characterized, well-tested products can help minimize risks. Finally, it is critical that additional research examine benefits and risks of DS use in cancer.

 —Mariann Garner-Wizard

Karppi J, Kurl S, Nurmi T, Rissanen TH, Pukkala E, Nyyssönen K. Serum lycopene and the risk of cancer: the Kuopio Ischaemic Heart Disease Risk Factor (KIHD) Study. Ann Epidemiol. 2009 Jul;19(7): 512-518.

Cancer is a leading cause of death worldwide, second only to mortality associated with heart disease. It is thought that nutritional factors play an important role in the prevention of chronic diseases, such as cancer, and it has been estimated that nearly one-third of all cancer deaths in the United States could have been prevented through dietary modification. For example, diets rich in fruit and vegetables have been shown to be associated with a lower risk of many cancers. Among various phytochemicals the carotenoids in fruit and vegetables have shown “considerable promise” in preventing cancer because of their antioxidative ability to reduce oxidative stress—a risk factor for cancer. Of the many carotenoids, lycopene’s ability to reduce the risk of prostate cancer has been studied the most. Dietary lycopene is derived primarily from tomatoes (Lycopersicon esculentum) and tomato products, but is also found in small amounts in pink grapefruit (Citrus x paradisi), watermelon (Citrullus lanatus), rose hip (Rosa spp.), apricot (Prunus armeniaca), guava (Psidium guajava), and papaya (Carica papaya). Lycopene is a potent antioxidant, and its anticancer activity has been shown both in vivo and in vitro. Its likely anticarcinogenic mechanisms of action include free radical scavenging, upregulation of detoxification systems, interruption of cell proliferation, and inhibition of cell cycle progression. The objective of the present study was to evaluate the association between serum lycopene concentrations and the risk of cancer in middle-aged eastern Finnish men in the Kuopio Ischaemic Heart Disease Risk Factor (KIHD) study.

 The KIHD study is an ongoing, population-based, prospective study designed to investigate cardiovascular disease risk factors and related outcomes in middle-aged men from eastern Finland. Residents of Kuopio and the surrounding rural communities (n = 2682) aged 42, 48, 54, or 60 years were enrolled for the baseline examinations between March 1984 and December 1989. Reexaminations took place every 4 years thereafter. Nine hundred ninety-seven men from the Finnish cohort had serum lycopene data available from the reexaminations that took place between 1991 and 1993 and comprised the study population for the present study. During the examinations, blood samples were collected for the measurement of serum lycopene, retinol, a-tocopherol, a-carotene, b-carotene, and folate concentrations. Physical activity, smoking habits, alcohol consumption, education level, and family history of cancer were assessed. In addition, waist-to-hip ratio and body mass index were measured. All cancers diagnosed in Finland are recorded in the National Cancer Registry. The incidence and type of cancer that developed in the Finnish cohort were derived from this registry. All cancers diagnosed in the cohort between the time of study entry (March 1991 to December 1993) and 31 December 2006 were included in the analysis.

 Over an average follow-up period of 12.6 years, 141 cancers were diagnosed: 55 prostate cancers, 17 lung cancers, 16 intestinal cancers, 10 urinary bladder cancers, and 43 cancers of other origin (e.g., stomach, lymphoma, skin, liver, kidney, and pancreas). The mean serum lycopene concentration was 0.12 mmol/L in the subjects who developed cancer and was 0.16 mmol/L in the subjects who did not develop cancer. Of the vitamins and carotenoids measured, serum lycopene was the only serum antioxidant that was significantly higher in men without cancer than in men with cancer and was the only carotenoid to have a negative correlation with cancer (r = -0.10, P = 0.003). More men with cancer than without cancer were smokers, and the duration of smoking was longer in the men with cancer than in those without cancer; smoking duration was inversely associated with serum lycopene concentration (r = -0.11; P < 0.0001). Men in the highest tertile of serum lycopene concentration had a 45% lower risk of overall cancer (risk ratio [RR] = 0.55; 95% confidence interval [CI] = 0.34–0.89; P = 0.015) and a 57% lower risk of other cancers (RR = 0.43; 95% CI = 0.23–0.79; P = 0.007) than did those in the lowest tertile of serum lycopene concentration after adjustment for the covariates age, examination years, family history of cancer, waist-to-hip ratio, duration of smoking, physical activity level, education level, alcohol consumption, and serum folate. No association between serum lycopene and prostate cancer was observed.

The results suggest that high serum lycopene concentrations may lower the risk of cancer, except for prostate cancer, in middle-aged men. However, the relatively small number of cancer cases in the cohort reduced the possibility of studying the risk of site-specific cancers. Also, the limitations to this study include obtaining only a single serum sample that simply demonstrates short-term dietary intake of lycopene due to its half-life of only a few days; multiple measurements would have been more precise.

 —Brenda Milot, ELS

Supplement users may have better cancer survival: Study

By Stephen Daniells, 31-Jul-2009

Warren L. Cargal, L. Ac.

Recently, I attended the Society for Integrative Oncology fifth international conference. There were many excellent research orientated studies demonstrating the positive effects of some Chinese herbals to inhibit cancer angiogenesis.

However what was most interesting to me were the presentations by several of the large teaching Universities, many of whom are now setting up in-house nutritional counselors to advise their patients during and after cancer treatments.

One revealing statistical statement was that if patients beginning cancer treatment were not taking supplements (herbs included), that by the end of their treatment 95 % of them would be taking some form of supplement.

Another statement made by one of the presenters was that she had lost count of how many patients show up in her office with a large bag of supplements wanting to know which one they should or should not be taking during or after their cancers treatments.

Currently most cancer treatments have no provisions for nutritional or botanical support and in effect most Oncologists either don’t understand or don’t support their use.

There is an extensive body of research demonstrating the ability of botanicals to inhibit angiogenesis, to activate protective properties of the body and stimulate regenerative processes.

Furthermore the use of some botanicals has been shown to decrease the toxic effects of chemotherapy, radiation and improve drug tolerance.

I thought it may be helpful to identify our basic post cancer treatment protocol and its rationale. Additions will be made based on the type of cancer and treatment modalities used. When approaching a disease like cancer it is important to formulate a balanced protocol that addresses (1) current weaknesses of the person (either pre or post cancer) (2) type of cancer and characteristics and (3) exogenous factors such as diet, lifestyle, and environment.

PectaSol Modified Citrus Pectin
Chemically, pectin is what’s known as a long-chain polysaccharide, a string of molecules comprised primarily of sugar (about two-thirds of its molecular structure closely resembles the sugar galactose). Given its constitution, pectin is particularly attractive to molecules that bind with galactose—and among these molecules is a class of carbohydrate-binding proteins called galectins.

Cancer cells carry a disproportionate number of these galectins—specifically galectin-3.

Hundreds of studies have pointed to the role of galectins in cancer development over the years—the most recent have exposed galectin-3 as a key player in the growth and spread of cancer within the body.

Galectin-3 promotes cancer progression in three interconnected ways:
• It allows cancer cells to attach to one another, forming groups that can survive in
your bloodstream and migrate to other parts of your body.
• Once cancer cells have formed a main tumor, galectins allow the cells to attach
themselves to new sites as well, forming secondary tumors.
• Lastly, galectin-3 nourishes malignant tumors by stimulating new blood vessel
growth (even where there was no blood supply before) to feed the tumor. This process is called angiogenesis.

Modified Citrus Pectin has a high affinity for galectins, binding these cells and preventing their spread and growth.

One study (published in the prestigious Journal of the National Cancer Institute) showed that administration of MCP reduced tumor metastasis by a remarkable 90 percent. These incredible results were supported two years later, in a follow-up study that demonstrated a similar decrease in melanoma cell adhesion—a phenomenon that the study authors attributed to MCP’s superior galectin-3 binding capabilities.

Platt D, Raz A. “Modulation of the lung colonization of B16-F1 melanoma cells by citrus pectin,” J Natl Cancer Inst, 1994; 84(6):438-42.

Ten Mushroom Formula
As immune stimulants, mushrooms can be used to help treat cancer and fight infections by initiating an immune response which results in higher levels of white blood cells, cytokines, antibodies and complement proteins. The cell walls of these mushrooms contain large polysaccharides called 1,3 ß-D-glucans linked to the chitin framework. These polysaccharides can also have smaller branching chains called 1,6 ß-D-glucans. Each mushroom has a different arrangement and degree of branching, which results in a different immune response. In addition, some mushrooms have 1,6 ß-D-glucans with 1,3 ß-D-glucan branching. A fragment of a mushroom ß-glucan serves as an antigen which a macrophage will display on its surface and present to T-helper cells. These T-helper cells will in turn release a variety of immune stimulating substances, cytokines, which will result in a cascade of immune responses. Cytokines released by both the macrophage and T-helper cells will cause a proliferation of T cells and B cells and stimulate production of complement proteins. Certain mushrooms, especially reishi, maitake and multi-mushroom blends, also dramatically increase the activity of natural killer cells and facilitate apoptosis of cancer cells resulting in the reduction of tumors. Macrophages and neutrophils will increase their levels of antimicrobial substances. These substances include antimicrobial enzymes and toxins, such as superoxide radical, hydrogen peroxide, hydroxyl radical, hydrochloruous acid and nitric oxide. These substances are produced in membrane-bound sacs, lysosomes, so they do not enter the cytoplasm of the white blood cell. When a macrophage or neutrophil envelopes a bacterium or virus, the microbe is enveloped within another membrane bound sac, a phagosome, which separates it from the cytoplasm of the phagocyte. Once a lysosome and phagosome merge, the toxins are released onto the microbe and destroy it (Delves 2006). The ß-glucan fragments thus serve to charge the immune system into an activated state making response to disease and infection much swifter and more effective.

Beta 1,3 Glucan
Numerous studies report that beta-1, 3-D glucan has anti-tumor and anti-cancer activity.[1],[2] In one study, intralesional administration of beta-1, 3-D glucans resulted in rapid tumor shrinkage. [3] In another study with mice, beta-1, 3-D glucan in conjunction with interferon gamma (INF-gamma) inhibited both the establishment of tumors and liver metastasis.[4] In some studies, beta-1, 3-D glucans enhanced the effects of chemotherapy. In studies on bladder cancer with mice, administration of cyclophosphamide, in conjunction with beta-1, 3-D glucans derived from yeast resulted in reduced mortality.[5] In human patients with advanced gastric or colorectal cancer, the administration of beta-1, 3-D glucans derived from shiitake mushrooms, in conjunction with chemotherapy (mitomycin C + 5-Fluorouracil) resulted in prolonged survival times compared to a control group receiving identical chemotherapy.[6]

Elevated cholesterol: Beta-glucans appear to be the major cholesterol lowering agents in oat bran fiber. Studies reveal that soluble glucans in oat bran can lower total cholesterol and LDL cholesterol levels in patients with hypercholesterolemia.[7],[8] Similar cholesterol lowering effects are reported in studies where barley is the source of beta glucans.[9]
Prevention of infection: 41 patients with multiple trauma (but no infections) were admitted to a double-blind trial to receive beta-1, 3-D glucan or a placebo. 11 of 20 controls contracted pneumonia vs only 2 of 21 treated with beta-1, 3-D glucan. Sepsis developed in 35% of controls vs 9.5% of those treated with glucan; deaths due to infection and general mortality in controls was 30% and 42.1% compared to 4.8% and 23.5% in the beta-1, 3-D glucan-treated group.[10]

Radiation exposure: In animal experiments, therapy with beta-1, 3-D glucans reportedly enhances recovery after radiation exposure and results in improvements in the bone marrow, spleen and white blood count.[11] ,[12]

Septic shock: Toxins from either external or internal (infections) sources cause leukocytes to release pro-inflammatory cytokines that can produce a series of biochemical events that ends in septic shock. Administration of soluble beta-1, 3/1/6 glucans reduces the production of pro-inflammatory cytokines, most notably Tumor Necrosis Factor-alpha (TNF-alpha), which reduced mortality.[13]

Surgery: In mice, treatment with beta-1, 3-D glucans either pre-or post-surgically reduced the production of nuclear factor-kappa B (NF-kappa B) and nuclear factor interleukin 6 (NF-IL6), which increased long-term survival approximately 40%.[14]

Wound healing: Macrophage activity is known to play a key role in wound healing from surgery or trauma. In both animal and human studies, therapy with beta glucan has provided improvements such as fewer infections, reduced mortality, and stronger tensile strength of scar tissue.

[1]Luzio N.R. Williams D.L. et al, “Comparative evaluation of the tumor inhibitory and antibacterial activity of solubilized and particulate glucan,” Recent Results Cancer Res 75:165-172. 1980.
[2] Morikawa K, Takeda R, Yamazaki M, et al., Induction of tumoricidal activity of polymorphonuclear leukocytes by a linear beta-1, 3-D-glucan and other immunomodulators in murine cells, Cancer Res. 1985 Apr; 45(4): 1496-501.
[3] Mansell PW, Ichinose H, Reed RJ, et al., “Macrophage-mediated destruction of human malignant cells in vivo,” J Natl Cancer Inst. 1975 Mar; 54(3): 571-80.
[4]Sveinbjornsson B, Rushfeldt C, Seljelid R, et al., “Inhibition of establishment and growth of mouse liver metastases after treatment with interferon gamma and beta-1, 3-D-glucan,” Hepatology. 1998 May; 27(5): 1241-8.
[5]Thompson IM, Spence CR, Lamm DL, et al., “Immunochemotherapy of bladder carcinoma with glucan and cyclophosphamide,” Am J Med Sci. 1987 Nov; 294(5): 294-300.
[6] Wakui A, Kasai M, Konno K, et al., “Randomized study of lentinan on patients with advanced gastric and colorectal cancer. Tohoku Lentinan Study Group,” Gan To Kagaku Ryoho. 1986 Apr; 13(4 Pt 1): 1050-9.
[7]Davidson MH; Dugan LD; Burns JH, et al., “The hypocholesterolemic effects of beta-glucan in oatmeal and oat bran. A dose-controlled study,” JAMA, 1991 Apr 10, 265:14, 1833-9.
[8]Braaten JT, Wood PJ, Scott FW, et al., “Oat beta-glucan reduces blood cholesterol concentration in hypercholesterolemic subjects,” Eur J Clin Nutr. 1994 Jul; 48(7): 465-74.
[9]McIntosh GH; Whyte J; McArthur R, et al., “Barley and wheat foods: influence on plasma cholesterol concentrations in hypercholesterolemic men,” Am J Clin Nutr, 1991 May, 53:5, 1205-9.
[10]de Felippe Junior J, da Rocha e Silva Junior M, Maciel FM, et al., “Infection prevention in patients with severe multiple trauma with the immunomodulator beta 1-3 polyglucose (glucan),” Surg Gynecol Obstet. 1993 Oct; 177(4): 383-8.
[11] Patchen ML; DiLuzio NR; Jacques P, et al., “Soluble polyglycans enhance recovery from cobalt-60-induced hemopoietic injury,” J Biol Response Mod, 1984 Dec, 3:6, 627-33.
[12]Petruczenko A, “Glucan effect on the survival of mice after radiation exposure,” Acta Physiol Pol. 1984 May-Jun; 35(3): 231-6.
[13]Soltys J, Quinn MT, “Modulation of endotoxin- and enterotoxin-induced cytokine release by in vivo treatment with beta- (1,6)-branched beta- (1,3)-glucan,” Infect Immun. 1999 Jan; 67(1): 244-52.
[14] Williams DL, Ha T, Li C, et al., “Inhibiting early activation of tissue nuclear factor-kappa B and nuclear factor interleukin 6 with (1–>3)-beta-D-glucan increases long-term survival in polymicrobial sepsis,” Surgery. 1999 Jul; 126(1): 54-65.

Resveratrol
Resveratrol is known for its ability to protect plants from bacteria and fungi. Purified versions have been described in scientific journals as potential anti-cancer, anti-inflammatory and anti-atherogenic agents, and for their ability to modulate cell growth.

Scientists found that Resveratrol apparently helps turn off a protein in the body that prevents cancer cells from being killed, as they should. The protein, called NF-kappa B, attaches to DNA inside cell nuclei and turns genes on and off like a switch.

In vitro resveratrol interacts with multiple molecular targets (see the mechanisms, and has positive effects on the cells of breast, skin, gastric, colon, esophageal, prostate, and pancreatic cancer, as well as leukemia.

Resveratrol interferes with all three stages of carcinogenesis — initiation, promotion and progression. Experiments in cell cultures of varied types and isolated subcellular systems in vitro imply many mechanisms in the pharmacological activity of resveratrol. In vitro, resveratrol “inhibited the proliferation of human pancreatic cancer cell lines.” In some lineages of cancer cell culture, resveratrol has been shown to induce apoptosis, which means it kills cells and may kill cancer cells. Resveratrol also possesses antioxidant and anti-angiogenic properties.

CoQ 10
The body also uses coenzyme Q10 as an antioxidant. An antioxidant is a substance that protects cells from chemicals called free radicals. Free radicals can damage DNA (deoxyribonucleic acid). Genes, which are pieces of DNA, tell the cells how to work in the body and when to grow and divide. Damage to DNA has been linked to some kinds of cancer. By protecting cells against free radicals, antioxidants help protect the body against cancer.

Low blood levels of coenzyme Q10 have been found in patients with myeloma, lymphoma, and cancers of the breast, lung, prostate, pancreas, colon, kidney, and head and neck.

Small studies have been done on the use of coenzyme Q10 after standard treatment in patients with breast cancer:
• In a study of coenzyme Q10 in 32 breast cancer patients, it was reported that some signs and symptoms of cancer went away in 6 patients. Details were given for only 3 of the 6 patients. The researchers also reported that all the patients in the study used less pain medicine, had improved quality of life, and did not lose weight during treatment.
• In a follow-up study, two patients who had breast cancer remaining after surgery were treated with high doses of coenzyme Q10 for 3 to 4 months. It was reported that after treatment with high-dose coenzyme Q10, the cancer was completely gone in both patients.
• In a third study led by the same researchers, 3 breast cancer patients were given high-dose coenzyme Q10 and followed for 3 to 5 years. The study reported that one patient had complete remission of cancer that had spread to the liver, another had remission of cancer that had spread to the chest wall, and the third had no breast cancer found after surgery.

Alpha Lipoic Acid
Free radical damage can promote the activity of a particular cell protein called NF kappa B. (NF-kB) NF-kB works to promote inflammation and genetic changes that have been linked with the development of cancer. Studies at the University of California at Berkley have found that when cells are bathed in ALA, NF-kB is inhibited thus preventing cell mutations from replicating. Researchers believe that this has significant implications in inhibiting the formation of cancerous tumors.

In various ways, lipoic acid appears to help restore a cellular “signaling” process that tends to break down in older blood vessels. It reduces mitochondrial decay in cells, which is closely linked to the symptoms of aging. With age, glutathione levels naturally decline, making older animals more susceptible to both free radicals and other environmental toxins – but lipoic acid can restore glutathione function to near normal. And the expression and function of other genes seems to come back to life.

Studies have shown that mice supplemented with lipoic acid have a cognitive ability, behavior, and genetic expression of almost 100% detoxification and antioxidant genes that are comparable to that of young animals.

Green Tea (ECGC extract from Green Tea)
Laboratory cell culture studies show that green tea polyphenols are powerful triggers of apoptosis (cell suicide) and cell cycle arrest in cancerous but not in normal cells. (Cell cycling is the process cells go through to divide and replicate.)
These anticancer actions have been assumed to be due to the powerful antioxidant effects of green tea’s catechins, especially epigallocatechin-3-gallate (EGCG). This is a reasonable assumption, given that a number of studies have shown that green tea possesses remarkable antioxidant properties. In one study published in the November 2004 issue of Mutation Research, EGCG’s protective antioxidant effects against several carcinogens were found to be 120% stronger than those of vitamin C.
One of these mechanisms is green tea’s ability to inhibit angiogenesis, the development of new blood vessels. Cancer cells, which are constantly attempting to divide and spread, have an endless appetite that can only be temporarily quieted by decreasing the number of blood vessels that supply them with nutrients. By inhibiting angiogenesis, green tea helps starve cancer.
Studies also show that green tea works at the genetic level, shutting off genes in cancerous cells that are involved in cell growth, while turning on those that instruct the cancer cells to self-destruct. EGCG has even been found to work as a pro-oxidant or free radical, but just inside cancer cells, where it causes so much damage that the cancer cells’ self-destruct mechanisms are triggered.

2009-06-15

Researchers concluded that cancer patients should undergo vitamin D screening after a recent study found high prevalence of deficiency among subjects regardless of nutritional status.

Conducted at the Cancer Treatment Centers of America (CTCA) researchers assessed 737 cancer patients (302 male and 435 female) between January and June of 2008.

Subjects were evaluated and assigned to one of three classes of nutritional status: well nourished, moderately malnourished and severely malnourished. The mean age at presentation was about 56 years (SD = 10.2) and the most common cancer types were lung (133, 18%), breast (131, 18%), colorectal (97, 13%), pancreatic (86, 12%), prostate (44, 6%) and ovarian (38, 5%).

“While emerging evidence suggests the protective role of vitamin D in cancer, vitamin D status is not routinely assessed in cancer patients despite the high prevalence of malnutrition in this population,” said Carolyn Lammersfeld, national director of nutrition for CTCA and a principal investigator in the study.

Before the study, researchers hypothesized that malnutrition could contribute to vitamin D deficiency and therefore expected mean serum 25-hydroxy-vitamin D [25(OH)D] levels to be significantly lower in malnourished oncology patients. However, contrary to what they expected, vitamin D deficiency was found to be prevalent in cancer regardless of nutritional status.

This study was presented at the American Society of Clinical Oncology (ASCO) annual meeting and publicly released on ASCO’s website.

By Stephen Daniells, 03-Jun-2009

Related topics: Antioxidants, carotenoids, Vitamins & premixes, Cancer risk reduction

Increased intakes of vitamins C and E and beta-carotene may reduce the risk of cancer of the uterus, according to a new review and meta-analysis of the science to date.

Writing in Cancer Causes and Control, US scientists report that for every 1,000 microgram increase per 1,000 kcal of diet of beta-carotene was associated with a 12 per cent reduction in the risk of endometrial cancer.

Similarly, for every 50 milligram increase per 1,000 kcal of vitamin C the risk of endometrial cancer was reduced by 15 per cent, and for every 5 milligram increase per 1,000 kcal of vitamin E the risk of endometrial cancer was reduced by 9 per cent.

Endometrial cancer is the fifth most common cancer among women worldwide – around 7,000 American women die from the disease annually – but incidence of the cancer varies more than 10-fold worldwide.

The results are based on data from 12 case-control studies, and intakes from supplements were not considered by the researchers, led by Elisa Bandera from the Cancer Institute of New Jersey.

“Although the current case-control data suggest an inverse relationship of endometrial cancer risk with dietary intakes of beta-carotene, vitamin C, and vitamin E from food sources, additional studies are needed, particularly cohort studies, to confirm an association,” cautioned the researchers.
Indeed, data from one prospective cohort study “provided little indication of an association”, said Bandera and her co-workers.

Commenting on the potential mechanism, the US-based researchers noted that antioxidant vitamins may reduce the risk of cancer by limiting oxidative damage to DNA.
Antioxidant controversy

A vast body of epidemiological studies has linked increased dietary intake of antioxidants from fruits and vegetables to reduced risks of a range of diseases including cancer, cardiovascular disease and diabetes.

However, when such antioxidants have been extracted and put into supplements the results, according to the randomized clinical trials (RCTs), do not always produce the same benefits, and may even be harmful.

These observations have led to much negative publicity about antioxidant supplements, particularly the more well-known vitamin E and beta-carotene.

The design of randomised clinical trials, following the drug- or evidence-based model has received much criticism.

In an editorial comment in the Journal of the American Medical Association, Peter Gann, MD, ScD, from the University of Illinois at Chicago, said: “…single-agent interventions, even in combinations, may be an ineffective approach to primary prevention in average-risk populations.”

Bandera worked in collaboration with scientists from the University of Medicine and Dentistry of New Jersey, the American Cancer Society, and Kaiser Permanente

Source: Cancer Causes and Control
July 2009, Volume 20, Number 5, Pages 699-711doi: 10.1007/s10552-008-9283-x
“Antioxidant vitamins and the risk of endometrial cancer: a dose-response meta-analysis”
Authors: E.V. Bandera, D.M. Gifkins, D.F. Moore, M.L. McCullough, L.H. Kushi

Cancer Institute, Chinese Academy of Medical Sciences, Beijing, Peoples Republic of China.
BACKGROUND: The General Population Nutrition Intervention Trial was a randomized primary esophageal and gastric cancer prevention trial conducted from 1985 to 1991, in which 29,584 adult participants in Linxian, China, were given daily vitamin and mineral supplements. Treatment with “factor D,” a combination of 50 microg selenium, 30 mg vitamin E, and 15 mg beta-carotene, led to decreased mortality from all causes, cancer overall, and gastric cancer. Here, we present 10-year follow-up after the end of active intervention. METHODS: Participants were assessed by periodic data collection, monthly visits by village health workers, and quarterly review of the Linxian Cancer Registry. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the cumulative effects of four vitamin and mineral supplementation regimens were calculated using adjusted proportional hazards models. RESULTS: Through May 31, 2001, 276 participants were lost to follow-up; 9727 died, including 3242 from cancer (1515 from esophageal cancer and 1199 from gastric cancer). Participants who received factor D had lower overall mortality (HR = 0.95, 95% CI = 0.91 to 0.99; P = .009; reduction in cumulative mortality from 33.62% to 32.19%) and gastric cancer mortality (HR = 0.89, 95% CI = 0.79 to 1.00; P = .043; reduction in cumulative gastric cancer mortality from 4.28% to 3.84%) than subjects who did not receive factor D. Reductions were mostly attributable to benefits to subjects younger than 55 years. Esophageal cancer deaths between those who did and did not receive factor D were not different overall; however, decreased 17% among participants younger than 55 (HR = 0.83, 95% CI = 0.71 to 0.98; P = .025) but increased 14% among those aged 55 years or older (HR = 1.14, 95% CI = 1.00 to 1.30; P = .47). Vitamin A and zinc supplementation was associated with increased total and stroke mortality; vitamin C and molybdenum supplementation, with decreased stroke mortality. CONCLUSION: The beneficial effects of selenium, vitamin E, and beta-carotene on mortality were still evident up to 10 years after the cessation of supplementation and were consistently greater in younger participants. Late effects of other supplementation regimens were also observed.

J Natl Cancer Inst. 2009 Apr 1;101(7):507-18. Epub 2009 Mar 24

Departments of Urology, Institute for Human Genetics, University of California at San Francisco, San Francisco, California 94143-0794, USA.

PURPOSE: Dietary intake of long-chain omega-3 (LC n-3) polyunsaturated fatty acids may reduce inflammation and in turn decrease risk of prostate cancer development and progression. This potential effect may be modified by genetic variation in cyclooxygenase-2 (COX-2), a key enzyme in fatty acid metabolism and inflammation. EXPERIMENTAL DESIGN: We used a case-control study of 466 men diagnosed with aggressive prostate cancer and 478 age- and ethnicity-matched controls. Diet was assessed with a semiquantitative food frequency questionnaire, and nine COX-2 tag single nucleotide polymorphisms (SNP) were genotyped. We used logistic regression models to estimate odds ratios (OR) for association and interaction. RESULTS: Increasing intake of LC n-3 was strongly associated with a decreased risk of aggressive prostate cancer (P(trend)

Clin Cancer Res. 2009 Apr 1;15(7):2559-66. Epub 2009 Mar 24