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Category: cancer

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The following medical article (actually an interview with Prof. Cedric F Garland, Department of Family & Preventive Medicine, University of California San Diego School of Medicine) is strongly in favor of Americans getting their Vitamin D levels tested, and taking vitamin D3 (if needed) to raise serum levels of vitamin D's metabolite 25(OH)D to at least 30 ng/mL and preferably more.

It is suggested that taking 1000 IU of vitamin D3 daily would achieve these levels in most people. From Medscape:

Vitamin D and Mortality Risk: Should Clinical Practice Change?

Traditionally associated with skeletal disease including osteoporosis and fractures, low levels of serum 25-hydroxyvitamin D (25[OH]D), the metabolite usually measured as a mark of vitamin D status, more recently have been linked to a wide range of nonskeletal diseases, including some cancers and autoimmune, cardiometabolic, and neurologic diseases. A number of studies also have reported an inverse association between 25(OH)D concentration and all-cause mortality.

To explore this association more, Medscape reached out to Dr. Cedric Garland, a well-known expert on vitamin D. Dr. Garland is a professor in the Division of Epidemiology, Department of Family and Preventive Medicine, and a Fellow of the American College of Epidemiology. He has a Doctor of Public Health degree from University of California San Diego and studied epidemiology at Johns Hopkins. His research has focused on vitamin D status in health and the association between vitamin D deficiency and increased risk for disease, including some common cancers (breast cancer, colon cancer, leukemia, and melanoma) and diabetes. He is active in seeking to reduce the risk for cancer and diabetes by improving vitamin D status among the US population.

To examine the relation between serum 25(OH)D and mortality, Dr. Garland and colleagues at the University of California San Diego and others in the United States pooled data from 32 studies published between 1966 and 2013.[6] They found an overall relative risk of 1.8 (95% confidence interval [CI]: 1.7-1.8; P <.001) comparing the lowest (0-9 ng/mL) with the highest (>30 ng/mL) category of 25(OH)D for all-cause mortality. Serum 25(OH)D concentrations ≤30 ng/mL were associated with higher all-cause mortality than concentrations >30 ng/mL (P <.01).

The investigators noted that these findings confirmed observations from the Institute of Medicine (IOM) that 25(OH)D levels of <20 ng/mL are too low for safety,[8] but they suggested a cut-off point of >30 ng/mL rather than >20 ng/mL for all-cause mortality reduction. This level "could be achieved in most individuals by intake of 1000 IU per day of vitamin D3," the investigators said, noting that this is described as a safe dose in almost all adults by both the IOM[8] and Endocrine Society[9] clinical guidelines on dietary intake of vitamin D.

In particular, a randomized clinical trial by Lappe et al[12] had demonstrated a reduced risk for all cancers with vitamin D supplementation in postmenopausal women.... Only one third of the US population is below 20 ng/mL,[15] but two thirds of the population is below 30 ng/mL.[16]

We decided to look at what would happen if we put together all the existing studies that have looked at the survival of "ordinary" people; that is, mostly people in general practices who did not, for the most part, have illnesses. Studies that only included people who were already ill were not eligible for inclusion in our analysis. We found 88 relevant studies, of which 32 presented their data by quartiles of intake, allowing us to see a dose response

The incidence of colon cancer is very high in countries like Iceland and Sweden, and other countries nearer the North Pole, and in countries like New Zealand, which is closer to the South Pole, and intermediate in countries at intermediate latitudes such as the United States, which is, on average, 38º north of the Equator. By the time you get down within the tropics, which is 23º from the Equator, it begins to decrease, and within 5º of the Equator there are vanishingly low incidence rates of colon cancer. In the past, some scientists theorized that the low incidence rates near the equator were due to intake of a high-fiber diet, but now my group believes -- and many others are leaning more in this direction -- that it is the high UVB irradiance and high circulating 25(OH)D year-around nearer the equator rather than a high-fiber diet that best explains the inverse association with solar UVB irradiance

Raising the serum 25(OH)D from 30 to 40 ng/mL reduces the incidence of breast, bowel, and lung cancer by 80%, as reported by Lappe and colleagues in their clinical trial.[12]On the other hand, if you lump all cancers together, in both sexes, and include countries where there is a whole lot of cigarette smoking, then you may obscure the effect of the vitamin D. Vitamin D is not able to overcome the effect of heavy smoking, and the CHANCES analysis[7] included data from people in countries like the Czech Republic, Poland, and Lithuania, where there is a huge amount of smoking. Although the effects are still there, they are weakened.

Studies such as our meta-analysis have provided us an opportunity to not just be locked into the present but to predict mortality on the basis of vitamin D levels in the present. I had expected our results to be convincing, but we were shocked at the persistence of the belief that very low levels of vitamin D, such as approximately 20 ng/mL, are safe. They are not safe with regard to breast and colon cancer, several other cancers, diabetes in youth and adulthood, fractures, and other complications of 25(OH)D <30 ng/mL. Even higher levels, such as 40-60 ng/mL, would be even safer, according to a letter of consensus of expert vitamin D scientists and physicians.

In addition, 2 ongoing trials, the CAPS study[23] (aiming to replicate the findings of Lappe et al[12]) and the VITAL study,[22] are both using a vitamin D3 dose of 2000 international units (IU)/day. I think that if I were to design a trial, knowing what we know today, I would use 4000-5000 IU/day. It seems as though each time we do a clinical trial, by the time the trial is completed, we know that the doses were too small to elicit an effect.

I am also concerned that there may be not enough calcium to see an effect. In CAPS, the women are being given 1500 mg of calcium, which was done in the original randomized controlled trial in which 80% of the cancers in postmenopausal women were prevented. I would have stayed with this design and dose for the VITAL trial. We know that it helps because in their original trial, Lappe and colleagues[12]examined the effects of vitamin D alone vs vitamin D plus calcium, and the effects were stronger when the calcium was included.

Testing should be universal. And ideally it should be done in March when the vitamin D is at its lowest levels. This will prevent hundreds of thousands of cases of serious diseases worldwide annually, beginning with postmenopausal breast cancer and including colon cancer and types 1 and 2 diabetes. Skipping this test would be equivalent to not measuring blood pressure, serum lipids, or weight at an annual exam.

No one should run a serum 25(OH)D less than 30 ng/mL. This means that two thirds of the US population needs supplementation. You may have noticed that President Obama was recently tested for his vitamin D, and it was 22.9 ng/mL.[35] His physicians wisely decided to treat him, and he is now taking vitamin D.

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Another study finding health benefits from eating dairy foods (vs not eating any dairy foods).

From Science Daily: A heart-felt need for dairy food: Small serving beneficial, large not necessary

A daily small serve of dairy food may reduce the risk of heart disease or stroke, even in communities where such foods have not traditionally formed part of the diet according to new research.

A study of nearly 4000 Taiwanese, led by Emeritus Professor Mark Wahlqvist from Monash University's Department of Epidemiology and Preventive Medicine and the Monash Asia Institute, considered the role increased consumption of dairy foods had played in the country's gains in health and longevity.

"We observed that increased dairy consumption meant lower risks of mortality from cardiovascular disease, especially stroke, but found no significant association with the risk of cancer," Professor Wahlqvist said.

Milk and other dairy foods are recognised as providing a broad spectrum of nutrients essential for human health. According to the study findings, people only need to eat small amounts to gain the benefits.

"Those who ate no dairy had higher blood pressure, higher body mass index and greater body fatness generally than other groups. But Taiwanese who included dairy food in their diet only three to seven times a week were more likely to survive than those who ate none."

For optimal results, the key is daily consumption of dairy foods -- but at the rate of about five servings over a week. One serving is the equivalent to eight grams of protein: a cup of milk, or 45 grams of cheese. Such quantities rarely cause trouble even for people considered to be lactose intolerant, Professor Wahlqvist said.

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Eating more tomatoes is doable, tastes delicious, and reduces prostate cancer risk! From Science Daily:

Fighting prostate cancer with tomato-rich diet

Men who eat over 10 portions a week of tomatoes have an 18 percent lower risk of developing prostate cancer, new research suggests. With 35,000 new cases every year in the UK, and around 10,000 deaths, prostate cancer is the second most common cancer in men worldwide. Rates are higher in developed countries, which some experts believe is linked to a Westernised diet and lifestyle.

To assess if following dietary and lifestyle recommendations reduces risk of prostate cancer, researchers at the Universities of Bristol, Cambridge and Oxford looked at the diets and lifestyle of 1,806 men aged between 50 and 69 with prostate cancer and compared with 12,005 cancer-free men.

The NIHR-funded study, published in the medical journal Cancer Epidemiology, Biomarkers and Prevention, is the first study of its kind to develop a prostate cancer 'dietary index' which consists of dietary components -- selenium, calcium and foods rich in lycopene -- that have been linked to prostate cancer. Men who had optimal intake of these three dietary components had a lower risk of prostate cancer.

Tomatoes and its products -- such as tomato juice and baked beans -- were shown to be most beneficial, with an 18 per cent reduction in risk found in men eating over 10 portions a week. This is thought to be due to lycopene, an antioxidant which fights off toxins that can cause DNA and cell damage. 

The researchers also looked at the recommendations on physical activity, diet and body weight for cancer prevention published by the World Cancer Research Fund (WCRF) and the American Institute for Cancer Research (AICR). Only the recommendation on plant foods -- high intake of fruits, vegetables and dietary fibre -- was found to be associated with a reduced risk of prostate cancer. 

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Here it is, a list of 17 cancers linked to being overweight or obese. From Science Daily:

Overweight and obesity linked to 10 common cancers, over 12,000 cases every year in UK

A higher body mass index (BMI) increases the risk of developing 10 of the most common cancers, the largest study of its kind on BMI and cancer, involving more than 5 million adults in the UK, shows. Each 5 kg/m² increase in BMI was clearly linked with higher risk of cancers of the uterus (62% increase), gallbladder (31%), kidney (25%), cervix (10%), thyroid (9%), and leukemia (9%). Higher BMI also increased the overall risk of liver, colon, ovarian, and breast cancers.

Using data from general practitioner records in the UK's Clinical Practice Research Datalink (CPRD), the researchers identified 5·24 million individuals aged 16 and older who were cancer-free and had been followed for an average of 7·5 years. The risk of developing 22 of the most common cancers, which represent 90% of the cancers diagnosed in the UK, was measured according to BMI after adjusting for individual factors such as age, sex, smoking status, and socioeconomic status. A total of 166 955 people developed one of the 22 cancers studied over the follow-up period. BMI was associated with 17 out of the 22 specific types of cancer examined.

Each 5 kg/m² increase in BMI was clearly linked with higher risk of cancers of the uterus (62% increase), gallbladder (31%), kidney (25%), cervix (10%), thyroid (9%), and leukemia (9%). Higher BMI also increased the overall risk of liver (19% increase), colon (10%), ovarian (9%), and breast cancers (5%), but the effects on these cancers varied by underlying BMI and by individual-level factors such as sex and menopausal status. Even within normal BMI ranges, higher BMI was associated with increased risk of some cancers.

There was some evidence that those with high BMI were at a slightly reduced risk of prostate cancer and premenopausal breast cancer. Based on the results, the researchers estimate that excess weight could account for 41% of uterine and 10% or more of gallbladder, kidney, liver, and colon cancers in the UK.

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Treating tumors with bacteria is very exciting and new.From Medical Express:

Injected bacteria shrink tumors in rats, dogs and humans

A modified version of the Clostridium novyi (C. noyvi-NT) bacterium can produce a strong and precisely targeted anti-tumor response in rats, dogs and now humans, according to a new report from Johns Hopkins Kimmel Cancer Center researchers.

In its natural form, C. novyi is found in the soil and, in certain cases, can cause tissue-damaging infection in cattle, sheep and humans. The microbe thrives only in oxygen-poor environments, which makes it a targeted means of destroying oxygen-starved cells in tumors that are difficult to treat with chemotherapy and radiation. The Johns Hopkins team removed one of the bacteria's toxin-producing genes to make it safer for therapeutic use.

For the study, the researchers tested direct-tumor injection of the C. noyvi-NT spores in 16 pet dogs that were being treated for naturally occurring tumors. Six of the dogs had an anti-tumor response 21 days after their first treatment. Three of the six showed complete eradication of their tumors, and the length of the longest diameter of the tumor shrunk by at least 30 percent in the three other dogs.

In a Phase I clinical trial of C. noyvi-NT spores conducted at MD Anderson Cancer Center, a patient with an advanced soft tissue tumor in the abdomen received the spore injection directly into a metastatic tumor in her arm. The treatment significantly reduced the tumor in and around the bone. "She had a very vigorous inflammatory response and abscess formation," according to Nicholas Roberts, Vet.M.B., Ph.D. "But at the moment, we haven't treated enough people to be sure if the spectrum of responses that we see in dogs will truly recapitulate what we see in people."

"One advantage of using bacteria to treat cancer is that you can modify these bacteria relatively easily, to equip them with other therapeutic agents, or make them less toxic as we have done here, " said Shibin Zhou, M.D., Ph.D., associate professor of oncology at the Cancer Center.  He and colleagues at Johns Hopkins began exploring C. novyi's cancer-fighting potential more than a decade ago after studying hundred-year old accounts of an early immunotherapy called Coley toxins, which grew out of the observation that some cancer patients who contracted serious bacterial infections showed cancer remission.

The researchers focused on soft tissue tumors because "these tumors are often locally advanced, and they have spread into normal tissue," said Roberts, a Ludwig Center and Department of Pathology researcher. The bacteria cannot germinate in normal tissues and will only attack the oxygen-starved or hypoxic cells in the tumor and spare healthy tissue around the cancer.

Verena Staedtke, M.D., Ph.D., a Johns Hopkins neuro-oncology fellow, first tested the spore injection in rats with implanted brain tumors called gliomas. Microscopic evaluation of the tumors showed that the treatment killed tumor cells but spared healthy cells just a few micrometers away. The treatment also prolonged the rats' survival, with treated rats surviving an average of 33 days after the tumor was implanted, compared with an average of 18 days in rats that did not receive the C. noyvi-NT spore injection.

Zhou said that study of the C. noyvi-NT spore injection in humans is ongoing, but the final results of their treatment are not yet available. "We expect that some patients will have a stronger response than others, but that's true of other therapies as well. Now, we want to know how well the patients can tolerate this kind of therapy."

It may be possible to combine traditional treatments like chemotherapy with the C. noyvi-NT therapy, said Zhou, who added that the researchers have already studied these combinations in mice. "Another good thing about using bacteria as a therapeutic agent is that once they're infecting the tumor, they can induce a strong immune response against tumor cells themselves," Zhou said.

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Excellent way to lower breast cancer risk. From Science Daily:

Postmenopausal breast cancer risk decreases rapidly after starting regular physical activity

Postmenopausal women who in the past four years had undertaken regular physical activity equivalent to at least four hours of walking per week had a lower risk for invasive breast cancer compared with women who exercised less during those four years, according to new data.

"Twelve MET-h [metabolic equivalent task-hours] per week corresponds to walking four hours per week or cycling or engaging in other sports two hours per week and it is consistent with the World Cancer Research Fund recommendations of walking at least 30 minutes daily," said Agnès Fournier, PhD, a researcher in the Centre for Research in Epidemiology and Population Health at the Institut Gustave Roussy in Villejuif, France. "So, our study shows that it is not necessary to engage in vigorous or very frequent activities; even walking 30 minutes per day is beneficial."

Postmenopausal women who in the previous four years had undertaken 12 or more MET-h of physical activity each week had a 10 percent decreased risk of invasive breast cancer compared with women who were less active. Women who undertook this level of physical activity between five and nine years earlier but were less active in the four years prior to the final data collection did not have a decreased risk for invasive breast cancer

"We found that recreational physical activity, even of modest intensity, seemed to have a rapid impact on breast cancer risk. However, the decreased breast cancer risk we found associated with physical activity was attenuated when activity stopped. As a result, postmenopausal women who exercise should be encouraged to continue and those who do not exercise should consider starting because their risk of breast cancer may decrease rapidly."

Fournier and colleagues analyzed data obtained from biennial questionnaires completed by 59,308 postmenopausal women who were enrolled in E3N, the French component of the European Prospective Investigation Into Cancer and Nutrition (EPIC) study. The mean duration of follow-up was 8.5 years, during which time, 2,155 of the women were diagnosed with a first primary invasive breast cancer.

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I have seen a lot of excitement about this research, especially whether several day fasting would be beneficial for other diseases (e.g., Crohn's disease) or even for middle-aged or older people who just want to boost their immune system. From Science Daily:

Fasting triggers stem cell regeneration of damaged, old immune system

In the first evidence of a natural intervention triggering stem cell-based regeneration of an organ or system, a study shows that cycles of prolonged fasting not only protect against immune system damage -- a major side effect of chemotherapy -- but also induce immune system regeneration, shifting stem cells from a dormant state to a state of self-renewal.

In both mice and a Phase 1 human clinical trial, long periods of not eating significantly lowered white blood cell counts. In mice, fasting cycles then "flipped a regenerative switch": changing the signaling pathways for hematopoietic stem cells, which are responsible for the generation of blood and immune systems, the research showed.

The study has major implications for healthier aging, in which immune system decline contributes to increased susceptibility to disease as we age. By outlining how prolonged fasting cycles -- periods of no food for two to four days at a time over the course of six months -- kill older and damaged immune cells and generate new ones, the research also has implications for chemotherapy tolerance and for those with a wide range of immune system deficiencies, including autoimmunity disorders.

"When you starve, the system tries to save energy, and one of the things it can do to save energy is to recycle a lot of the immune cells that are not needed, especially those that may be damaged," Longo said. "What we started noticing in both our human work and animal work is that the white blood cell count goes down with prolonged fasting. Then when you re-feed, the blood cells come back. So we started thinking, well, where does it come from?"

Prolonged fasting forces the body to use stores of glucose, fat and ketones, but also breaks down a significant portion of white blood cells. Longo likens the effect to lightening a plane of excess cargo.

During each cycle of fasting, this depletion of white blood cells induces changes that trigger stem cell-based regeneration of new immune system cells. In particular, prolonged fasting reduced the enzyme PKA, an effect previously discovered by the Longo team to extend longevity in simple organisms and which has been linked in other research to the regulation of stem cell self-renewal and pluripotency -- that is, the potential for one cell to develop into many different cell types. Prolonged fasting also lowered levels of IGF-1, a growth-factor hormone that Longo and others have linked to aging, tumor progression and cancer risk.

"PKA is the key gene that needs to shut down in order for these stem cells to switch into regenerative mode. It gives the 'okay' for stem cells to go ahead and begin proliferating and rebuild the entire system," explained Longo, noting the potential of clinical applications that mimic the effects of prolonged fasting to rejuvenate the immune system. "And the good news is that the body got rid of the parts of the system that might be damaged or old, the inefficient parts, during the fasting. Now, if you start with a system heavily damaged by chemotherapy or aging, fasting cycles can generate, literally, a new immune system."

Prolonged fasting also protected against toxicity in a pilot clinical trial in which a small group of patients fasted for a 72-hour period prior to chemotherapy, extending Longo's influential past research: "While chemotherapy saves lives, it causes significant collateral damage to the immune system. The results of this study suggest that fasting may mitigate some of the harmful effects of chemotherapy," said co-author Tanya Dorff, assistant professor of clinical medicine at the USC Norris Comprehensive Cancer Center and Hospital. 

"We are investigating the possibility that these effects are applicable to many different systems and organs, not just the immune system," said Longo, whose lab is in the process of conducting further research on controlled dietary interventions and stem cell regeneration in both animal and clinical studies.

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Very interesting. Gives people a way to eat red meat, but not increase their colorectal cancer risk (by also eating resistant starch, e.g., potato salad or beans). From Science Daily:

Eating resistant starch may help reduce red meat-related colorectal cancer risk

Consumption of a type of starch that acts like fiber may help reduce colorectal cancer risk associated with a high red meat diet, according to a study. "Red meat and resistant starch have opposite effects on the colorectal cancer-promoting miRNAs, the miR-17-92 cluster," said one researcher. "This finding supports consumption of resistant starch as a means of reducing the risk associated with a high red meat diet.

Unlike most starches, resistant starch escapes digestion in the stomach and small intestine, and passes through to the colon (large bowel) where it has similar properties to fiber, Humphreys explained. Resistant starch is readily fermented by gut microbes to produce beneficial molecules called short-chain fatty acids, such as butyrate, she added.

"Good examples of natural sources of resistant starch include bananas that are still slightly green, cooked and cooled potatoes [such as potato salad], whole grains, beans, chickpeas, and lentils. Scientists have also been working to modify grains such as maize so they contain higher levels of resistant starch," said Humphreys.

After eating 300 g of lean red meat per day for four weeks, study participants had a 30 percent increase in the levels of certain genetic molecules called miR-17-92 in their rectal tissue, and an associated increase in cell proliferation. Consuming 40 g of butyrated resistant starch per day along with red meat for four weeks brought miR-17-92 levels down to baseline levels.

The study involved 23 healthy volunteers, 17 male and six female, ages 50 to 75. Participants either ate the red meat diet or the red meat plus butyrated resistant starch diet for four weeks, and after a four-week washout period switched to the other diet for another four weeks.

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Great reason to enjoy spicy food. From Science Daily:

Chili peppers for a healthy gut: Spicy chemical may inhibit gut tumors

Researchers report that dietary capsaicin – the active ingredient in chili peppers – produces chronic activation of a receptor on cells lining the intestines of mice, triggering a reaction that ultimately reduces the risk of colorectal tumors.

...the current study suggests one potential remedy might be spicy capsaicin, which acts as an irritant in mammals, generating a burning sensation in contact with tissue. Capsaicin is already broadly used as an analgesic in topical ointments, where its properties as an irritant overwhelm nerves, rendering them unable to report pain for extended periods of time. It's also the active ingredient in pepper spray.

The researchers fed capsaicin to mice genetically prone to developing multiple tumors in the gastrointestinal tract. The treatment resulted in a reduced tumor burden and extended the lifespans of the mice by more than 30 percent. The treatment was even more effective when combined with celecoxib, a COX-2 non-steroidal anti-inflammatory drug already approved for treating some forms of arthritis and pain.

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This research review suggests that 5 servings a day of fruits and vegetables has the best health benefits. They surprisingly did not find that fruit/vegetable consumption was protective against cancer. But the authors point out that other studies of cancer and fruit/vegetable consumption have also been inconsistent, and this might be partly explained if certain fruits and vegetables only have effects on certain cancers. From Medical Daily:

An Apple A Day Keeps The Doctor Away? Actually It's 5 Apples, And They Keep Death Away

A review of the eating habits of more than 800,000 people seems to discredit the old maxim about "an apple a day." In fact, five servings of fruit and vegetables offers the best health benefits, particularly against heart disease, and reduces your chances of dying for any reason.

After calculating the odds, researchers write in the Journal of Epidemiology and Community Health that "the risk of all-cause mortality was decreased by 5 percent for each additional serving a day of fruit and vegetables." But, contrary to other reports, they found the benefits drop off after five servings, at which point, they wrote, "we observed a threshold." Previous studies have said seven fruit and vegetable servings is the optimum number.

Other studies have also made the case for fruits and vegetables as a ward against cancer. This one, led by Professor Frank B. Hu in the Harvard School of Public Health, saw no evidence for that. They did, however, find a "significant inverse association" between a fruit and veggie diet and death by heart disease. "The results support current recommendations to increase consumption to promote health and overall longevity," Hu and his colleagues wrote.

Of course, the authors admit, the studies they looked at may have been corrupted by participants lying or guessing on their diet questionnaires. But one thing this study has going for it is the massive sample size. They looked at 16 papers involving 833,234 people and 56,423 deaths. Most of those deaths — as is the case in the general population — were caused by cardiovascular disease and cancer. The people who lived longest adhered to what's called the Mediterranean diet, which favors carrots and tomatoes to steak and bacon.