Dr. Kevin Patterson on Western Diets and Health

A few readers have pointed me to an interesting NPR interview with the Canadian physician Kevin Patterson (link). He describes his medical work in Afghanistan and the Canadian arctic treating cultures with various degrees of industrialization. He discusses the "epidemiological transition", the idea that cultures experience predictable changes in their health as they go from hunter-gatherer, to agricultural, to industrial. I think he has an uncommonly good perspective on the effects of industrialization on human health, which tends to be true of people who have witnessed the effects of the industrial diet and lifestyle on diverse cultures.

A central concept behind my thinking is that it's possible to benefit simultaneously from both:

• The sanitation, medical technology, safety technology, law enforcement and lower warfare-related mortality that have increased our life expectancy dramatically relative to our distant ancestors.


• The very low incidence of obesity, diabetes, coronary heart disease and other non-infectious chronic diseases afforded by a diet and lifestyle roughly consistent with our non-industrial heritage.

But it requires discipline, because going with the flow means becoming unhealthy.

NEOADJUVANT ANDROGEN DEPRIVATION THERAPY BEFORERADIOTHERAPY HALVES PROSTATE CANCER MORTALITY

New long-term results confirm the finding that neoadjuvant androgen-deprivation therapy (ADT), combined with radiotherapy, can significantly boost survival in men with locally advanced prostate cancer.
The updated results of the Trans-Tasman Radiation Oncology Group (TROG) 96.01 trial are published online March 25 in the Lancet Oncology.
They show that a large proportion of patients with locally advanced disease can be successfully treated with as little as 6 months of neoadjuvant ADT and a relatively low dose of radiation.
The authors note that at 10 years, neoadjuvant ADT cut the prostate-cancer-specific mortality rate in half, compared with radiation treatment alone (11% vs 22%).
All-cause mortality was also reduced, by about a third, among patients who received both therapies (29% vs 43%).
These results confirm the use of neoadjuvant ADT in this population of prostate cancer patients, explained lead author James W. Denham, MD, director of the Prostate Cancer Trials Group at the University of Newcastle, New South Wales, Australia. "It also gives evidence that the treatment needs to be at least 6 months to have an effect on mortality."
"For men with intermediate-risk cancers, RTOG [Radiation Therapy Oncology Group] 9408 has shown that 4 months of neoadjuvant ADT can improve survival," he told Medscape Medical News.
Earlier Results Confirmed
Dr. Denham and colleagues previously reported 5-year results from this study. They suggested that 6 months of neoadjuvant ADT improved prostate-cancer-specific survival by reducing metastases (Lancet Oncol. 2005;6:841-850). At 10 years, they now find that, compared with radiotherapy alone, the addition of ADT improves event-free survival, decreases the cumulative incidence of prostate-specific antigen (PSA) progression, and decreases distant progression and all-cause and disease-specific mortality.
In this prostate cancer population, neoadjuvant ADT for at least 6 months is the already the standard of care in Australia and New Zealand and a number of centers in other parts of the world, explained Dr. Denham.
He also noted that although a longer duration of ADT after radiation might increase survival slightly, which has been seen in some trials from the RTOG and European Organization for Research and Treatment of Cancer, it comes at a cost — both financially and in terms of toxicity. "A point we make in the article is that the informed treatment-consent process is getting much more rigorous in many countries, and it is getting more difficult to 'persuade' men that the inconvenience and potential prolonged ill effects of long-term ADT are worth the possible additional gains," he said.
"Six months of neoadjuvant ADT and radiation is a very reasonable choice, particularly for men with coexisting medical problems that could be exacerbated by long-term ADT," Dr. Denham added.
Clear Messages for Clinical Practice
In an accompanying editorial, Chris Parker, MD, consultant clinical oncologist from the Royal Marsden Hospital, Sutton, United Kingdom, agrees that these findings strengthen the evidence and send "2 clear messages for current clinical practice."
First off, he writes, is that it offers confirmation that neoadjuvant ADT "significantly reduces mortality after radiotherapy for high-risk prostate cancer, and is a standard of care."
The second point is that it helps to" resolve the uncertainty" regarding the duration of this therapy, and strongly suggests that the duration should be at least 6 months, he notes.
Six Months Superior to 3 Months
The TROG 96.01 study compared radiotherapy alone with 3 or 6 months of neoadjuvant ADT, which was given before and during radiation therapy. In their paper, the authors report, from the 10-year data, the benefits derived from 3 months and 6 months of neoadjuvant ADT.
Their analysis involved 802 men with stage T2b, T2c, T3, and T4 N0M0 prostate cancers. They were randomly assigned to receive radiotherapy alone (n = 270), 3 months of neoadjuvant ADT plus radiotherapy (n = 265), or 6 months of neoadjuvant ADT plus radiotherapy (n = 267).
At 10 years, prostate-cancer-specific mortality was 22% for radiotherapy alone, 18.9% for 3 months of neoadjuvant therapy (hazard ratio [HR], 0.86; P = .398), and 11.4% for 6 months of neoadjuvant ADT (HR, 0.49; P = .0008).
For all-cause mortality at 10 years, the findings were similar: 42.5% for radiotherapy alone, 36.7% for 3 months of neoadjuvant ADT (HR, 0.84; P = .18), and 29.2% for 6 months of neoadjuvant ADT (HR, 0.63; P = .0008).
Conversely, the cumulative incidence of deaths at 10 years not related to prostate cancer were similar in all treatment groups: 20.4% for radiotherapy alone, 17.7% for 3 months of neoadjuvant ADT, and 17.8% for 6 months of neoadjuvant ADT (P > .40 for all paired comparisons).
During the course of the study, 16,562 PSA levels were obtained from the 802 men; the median number of PSA levels per patient was 21 (range, 1 to 43).
Progression of PSA was observed in 508 men. At 10 years, the cumulative incidence of PSA progression was 73.8% for radiotherapy alone, 60.4% for 3 months of neoadjuvant ADT (HR, 0.72; P = .003), and 52.3% for 6 months of neoadjuvant ADT (HR, 0.57; P < .0001).
Progression of the primary tumor was found in 179 men, and progression at distant sites was found in 226 men. The 10-year cumulative incidence of local progression as a first event was 28.2% for radiotherapy alone, 15.7% for 3 months of neoadjuvant ADT (HR, 0.49; P = .0005), and 13.3% for 6 months of neoadjuvant ADT (HR, 0.45; P < .0001).
More Data to Come
The authors note that data from the RTOG 92.02 study showed that patients with high Gleason scores received the most benefit from prolonged ADT, raising the possibility that "the morbidity of long-term androgen deprivation can be restricted to men with the highest risk of progression."
Although subgroup analyses of prostate-cancer-specific mortality data in TROG 96.01 did not support this hypothesis, the authors explain that the interpretation of the trial's pathology data is limited by lack of a centralized histopathologic review.
"We hope that this trial's successor, TROG 03.04 RADAR34 — which investigates adding 12 months of adjuvant ADT, with or without 18 months of zoledronate, to 6-month neoadjuvant ADT and radiotherapy — can help resolve this possibility," they write.
The study was funded by Australian Government National Health, the Medical Research Council, Hunter Medical Research Institute, AstraZeneca, and Schering-Plough. The authors and the editorialist have disclosed no relevant financial relationships.

Randy Tobler Show: Welcome

This morning, I had a conversation with Dr. Randy Tobler on his radio show "Vital Signs", on 97.1 FM News Talk in St Louis. Dr. Tobler is an obstetrician-gynecologist with an interest in nutrition, fitness and reproductive endocrinology from a holistic perspective. He asked me to appear on his show after he discovered my blog and found that we have some things in common, including an interest in evolutionary/ancestral health. We talked about the history of the American diet, the health of non-industrial cultures, what fats are healthiest, and the difference between pastured and conventional meat/dairy-- we took a few questions from listeners-- it was fun.

The show is available as a podcast here (3/26 show), although as far as I can tell, you need iTunes to listen to it. My section of the show starts around 8:20.

To everyone who arrived here after hearing me on the air this morning: welcome! Here are a few posts to give you a feel for what I do here at Whole Health Source:

The Coronary Heart Disease Epidemic
US Weight, Lifestyle and Diet Trends, 1970-2007
Butter vs. Margarine Showdown
Preventing and Reversing Tooth Decay
The Kitavans: Wisdom from the Pacific Islands
Potatoes and Human Health, Part I, Part II and Part III
Traditional Preparation Methods Improve Grains' Nutritional Value
Real Food XI: Sourdough Buckwheat Crepes
Glucose Tolerance in Non-industrial Cultures
Tropical Plant Fats: Palm Oil
It's Time to Let Go of the Glycemic Index

Safflower Oil Study

A few people have sent me a new study claiming to demonstrate that half a tablespoon of safflower oil a day improves insulin sensitivity, increases HDL and decreases inflammation in diabetics (1). Let me explain why this study does not show what it claims.

It all comes down to a little thing called a control group, which is the basis for comparison that you use to determine if your intervention had an effect. This study didn't have one for the safflower group. What it had was two intervention groups, one given 6.4g conjugated linoleic acid (CLA; 50% c9t11 and 50% t10c12-CLA) per day, and one given 8g safflower oil. I have to guess that this study was originally designed to test the effects of the CLA, with the safflower oil group as the control group, and that the interpretation of the data changed after the results came in. Otherwise, I don't understand why they would conduct a study like this without a control group.

Anyway, they found that the safflower oil group did better than the CLA group over 16 weeks, showing a higher insulin sensitivity, higher HDL, lower HbA1c (a marker of average blood glucose levels) and lower CRP (a marker of inflammation). But they also found that the safflower group improved slightly compared to baseline, therefore they decided to attribute the difference to a beneficial effect of safflower oil. The problem is that without a control (placebo) group for comparison, there's no way to know if the improvement would have occurred regardless of treatment, due to the season changing, more regular check-ups at the doctor's office due to participating in a study, or countless other unforeseen factors. A control group is essential for the accurate interpretation of results, which is why drug studies always have placebo groups.

What we can say is that the safflower oil group fared better than the CLA group, because there was a difference between the two. However, what I think really happened is that the CLA supplement was harmful and the small dose of safflower oil had no effect. Why? Because the t10c12 isomer of CLA, which was half their pill, has already been shown by previous well-controlled studies to reduce insulin sensitivity, decrease HDL and increase inflammatory markers at a similar dose and for a similar duration (2, 3). The safflower oil group only looked good by comparison. We can add this study to the "research bloopers" file.

It's worth noting that naturally occurring CLA mixtures, similar to those found in pastured dairy and ruminant fat, have not been shown to cause metabolic problems such as those caused by isolated t10c12 CLA.

BELIMUMAB: A NEW DRUG FOR LUPUS

The US Food and Drug Administration (FDA) has approved the use of belimumab (Benlysta, Human Genome Sciences and GlaxoSmithKline) in combination with standard therapies to treat active autoantibody-positive systematic lupus erythematosus.
This is the first lupus drug to be approved since 1955, when the FDA approved hydroxychloroquine (Plaquenil) and corticosteroids. In 1948, aspirin was approved to treat lupus.
Belimumab is a B-lymphocyte stimulator protein inhibitor that is thought to decrease the amount of abnormal B cells, which is hypothesized to be a mechanism of action in lupus.
The safety and effectiveness of belimumab was demonstrated in 2 clinical trials that randomized a total of 1684 patients to receive either belimumab or placebo in combination with standard therapy. Treatment with belimumab plus standard therapy reduced disease activity and possibly decreased the number of severe flares and steroid use.
Patients with active lupus that involved the kidneys or central nervous system and those who were previously treated with a B-cell-targeted therapy or intravenous cyclophosphamide were excluded from participating in the trials.
Study participants of African American or African descent did not significantly respond to belimumab. Additional studies will be conducted to definitively determine the safety and efficacy of belimumab in this population.
Common adverse effects reported with belimumab include nausea, diarrhea, fever, and infusion-site reactions. It is suggested that patients be treated with an antihistamine prior to a belimumab infusion.
A greater number of deaths and serious infections were reported in patients treated with belimumab than in those treated with placebo. Live vaccines should not be administered during treatment with belimumab.
It is estimated that lupus afflicts up to 1.5 million Americans, and it disproportionately affects black women.

New Ancestral Diet Review Paper

Pedro Carrera-Bastos and his colleagues Maelan Fontes-Villalba, James H. O'Keefe, Staffan Lindeberg and Loren Cordain have published an excellent new review article titled "The Western Diet and Lifestyle and Diseases of Civilization" (1). The paper reviews the health consequences of transitioning from a traditional to a modern Western diet and lifestyle. Pedro is a knowledgeable and tireless advocate of ancestral, primarily paleolithic-style nutrition, and it has been my privilege to correspond with him regularly. His new paper is the best review of the underlying causes of the "diseases of civilization" that I've encountered. Here's the abstract:

It is increasingly recognized that certain fundamental changes in diet and lifestyle that occurred after the Neolithic Revolution, and especially after the Industrial Revolution and the Modern Age, are too recent, on an evolutionary time scale, for the human genome to have completely adapted. This mismatch between our ancient physiology and the western diet and lifestyle underlies many so-called diseases of civilization, including coronary heart disease, obesity, hypertension, type 2 diabetes, epithelial cell cancers, autoimmune disease, and osteoporosis, which are rare or virtually absent in hunter–gatherers and other non-westernized populations. It is therefore proposed that the adoption of diet and lifestyle that mimic the beneficial characteristics of the preagricultural environment is an effective strategy to reduce the risk of chronic degenerative diseases.

At 343 references, the paper is an excellent resource for anyone with an academic interest in ancestral health, and in that sense it reminds me of Staffan Lindeberg's book Food and Western Disease. One of the things I like most about the paper is that it acknowledges the significant genetic adaptation to agriculture and pastoralism that has occurred in populations that have been practicing it for thousands of years. It hypothesizes that the main detrimental change was not the adoption of agriculture, but the more recent industrialization of the food system. I agree.

I gave Pedro my comments on the manuscript as he was editing it, and he was kind enough to include me in the acknowledgments.

REDUCING CHEMORADIOTHERAPY SAFE FOR SOMERABDOMYOSARCOMAS

NEW YORK (Reuters Health) Mar 03 - Reducing the use of radiotherapy and eliminating cyclophosphamide has been found safe and effective in some patients with newly diagnosed, low-risk embryonal rhabdomyosarcoma (ERMS).
The findings are the latest from The Intergroup Rhabdomyosarcoma Study Group (IRSG), and were published online February 28th in the Journal of Clinical Oncology.
In previous studies the same researchers who conducted this study found that patients with localized, grossly resected, or gross residual (orbital only) ERMS had 5-year failure-free survival rates of 83% and overall survival rates of 95%. That was using specially designed protocols for low-risk patients established by the IRSG. Those regimens included vincristine and dactinomycin with or without cyclophosphamide and radiation therapy.
The aim of the present study was to see if it was feasible, in a similar cohort of patients, to decrease toxicity by reducing radiotherapy doses and eliminating cyclophosphamide in patients at lowest risk.
The researchers stratified 342 patients by risk. The lower risk group (n=264) included embryonal ectomesenchymoma or ERMS patients categorized as stage 1 group I/IIA, stage 1 group III orbit, or stage 2 group I.
The higher risk group (n=78) included patients with stage 1 group IIB/C, stage I group III nonorbit, stage 2 group II, or stage 3 group I/II ERMS.
The researchers' specific objectives were three-fold:
1. To estimate failure-free survival rates of patients in subgroup A after vincristine and dactinomycin chemotherapy for 45 weeks, plus radiation therapy for patients with residual tumor;
2. To estimate failure-free survival rates of patients in subgroup B after vincristine and dactinomycin plus cyclophosphamide for 45 weeks, plus radiation therapy for patients with residual tumors;
3. And to ascertain local control and failure-free survival rates in three selected groups of patients given radiation therapy doses 5-10 Gy lower than in previous studies: 36 Gy for stage 1 group IIA, 45 Gy for stage 1 group III N0 orbit, and 36 Gy for stages 2/3 group IIA patients.
Estimated 5-year failure-free survival rates were 89% for patients in the lower risk group, and 85% for the higher risk group, after median follow-up of 5.1 years.
For patients with stage 1 group IIA tumors (n=62), estimated 5-year failure-free survival rates were 81%. For patients with group III orbit tumors (n=77), estimated 5-year failure-free survival was 86%.
The study group says 5-year failure-free survival and overall survival were similar to that observed in IRS-III patients, including those that were treated with reduced doses of radiation. Failure-free survival and overall survival were lower, however, than comparable IRS-IV patients that received vincristine and dactinomycin plus cyclophosphamide. Five-year failure-free survival rates were similar among the lower risk and higher risk patients.
Rhabdomyosarcoma is the most common type of soft-tissue sarcoma in children. The annual incidence of the disease in the U.S. is 4.5 cases per 1 million children younger than 14 years. About 250 new cases are diagnosed each year, nearly two thirds being embryonal rhabdomyosarcomas.

Gluten-Free January Survey Data, Part II: Health Effects of a Gluten-Free Diet

GFJ participants chose between three diet styles: a simple gluten-free diet; a "paleo light" diet diet that eliminated sugar and industrial seed (vegetable) oils in addition to gluten; and a "paleo full monty" diet that only included categories of food that would have been available to our pre-agricultural ancestors. The data in this post represent the simple gluten-free diet group, and do not represent the other two, which I'll analyze separately.

To get the data I'll be presenting below, first I excluded participants who stated on the survey that they did not adhere to the diet. Next, I excluded participants who were gluten-free before January, because they would presumably not have experienced a change from continuing to avoid gluten. That left us with 53 participants.

For each of these graphs, the vertical axis represents the number of participants in each category. They won't necessarily add up to 53, for several reasons. The most common reason is that for the questions asking about changes in health conditions, I didn't include responses from people who didn't have the condition in question at baseline because there was nothing to change.

Question #1: What is your overall opinion of the effect of gluten free January on you?

Participants had a very positive experience with the gluten-free diet. Not one person reported a negative overall experience.

Question #2: Did you note a weight change at the end of gluten free January?

And here are the data for people who described themselves as overweight at baseline:

Two-thirds of people who were overweight at baseline lost weight, and only one person out of 37 gained weight. That is striking. A number of people didn't weigh themselves, which is why the numbers only add up to 37.

Question #3: Before January 2011, did you have a problem with intestinal transit (frequent constipation or diarrhea)? If so, did your symptoms change during the month of January?


Responses are heavily weighted toward improvement, although there were a few instances where transit worsened. Transit problems are one of the most common manifestations of gluten sensitivity.

Question #4: Before January 2011, did you have frequent digestive discomfort (pain, bloating, etc.)? If so, did your symptoms change during the month of January?


Digestive discomfort was common, and the gluten-free diet improved it in nearly everyone who had it at baseline. I find this really impressive.

Question #5: Before January 2011, did you have acid reflux? If so, did your symptoms change during the month of January?

Acid reflux responded well to a gluten-free diet.

Question #6: Before January 2011, did you have a problem with tiredness/lethargy? If so, did your symptoms change during the month of January?
Lethargy was common and generally improved in people who avoided gluten. This doesn't surprise me at all. The recent controlled gluten study in irritable bowel syndrome patients found that lethargy was the most reliable consequence of eating gluten that they measured (1, 2). That has also been my personal experience.

Question #7: Before January 2011, did you have a problem with anxiety? If so, did your symptoms change during the month of January?

Anxiety tended to improve in most participants who started with it.

Question #8: Before January 2011, did you have a problem with an autoimmune or inflammatory condition? If so, did your symptoms change during the month of January?

Autoimmune and inflammatory conditions tended to improve in the gluten-free group, although one person experienced a worsening of symptoms.

Question #9: If you ate gluten again or did a gluten challenge after gluten free January, what was the effect?

Just under half of participants experienced moderate or significant negative symptoms when they re-introduced gluten at the end of the month. Two people felt better after re-introducing gluten.


Conclusion

I find these results striking. Participants overwhelmingly improved in every health category we measured. Although the data may have been somewhat biased due to the 53% response rate, it's indisputable that a large number of participants, probably the majority, benefited from avoiding gluten for a month. At some point, we're going to compile some of the comments people left in the survey, which were overwhelmingly positive. Here's a typical comment in response to the question " In your own words, how would you describe your January 2011 experience" (used with permission):

Amazing! I would recommend the experiment to anyone. I felt completely more alert, and less bloated. When I ate some gluten at the close of the experiment, I felt gross, bloated, and lethargic.

I think it's worth mentioning that some participants also eliminated other starches, particularly refined starches. Judging by the comments, the diet was probably lower in carbohydrate for a number of participants. We may try to assess that next year.

Gluten-Free January Survey Data, Part I: Demographics and Limitations

Thanks to Matt Lentzner for organizing Gluten-Free January, and everyone who participated and completed the survey, we have a nice data set illustrating what happens when a group of people stop eating gluten for a month. Janine Jagger, Matt and I have been busy analyzing the data, and I'm ready to begin sharing our findings.

GFJ had over 500 participants, 527 of which received the survey and 279 of which completed the survey at the end of the month. Of those who received the survey, 53 percent completed it. I think these are respectable numbers for a survey of this nature, and it reflects the conscientious nature of the people who participated in GFJ.

Demographics

Although respondents were primarily from the United States, I'm happy to say that the data represent 18 different nationalities:

Respondents represented a diversity of ages, the largest group being 30-39 years old, with similar numbers in the 20-29 and 40-49 year groups.
Respondents were just under 2/3 women.

Respondents represented a variety of weights, but the sample was biased toward lean people, in comparison with the general population. There were not many obese participants.
Overall, I was pleased to see that the demographics were quite diverse, particularly in the age and gender categories.

Limitations

There are a few caveats to keep in mind when interpreting the survey results:

1. GFJ participants do not represent a random cross-section of the population at large. They represent primarily health-conscious individuals who were motivated enough to make a substantial dietary change. In addition, many of the people who participated probably did so because they already suspected they had a problem with gluten.
   
2. The survey response rate was 53%. Although I think that's a reasonable number considering the circumstances, it leaves open the possibility that survey responders differ from non-responders. It's conceivable that participants with better adherence and better outcomes were more likely to complete the survey than those who did not adhere to the diet or had neutral or unfavorable outcomes, despite our efforts to encourage everyone to complete the survey regardless of adherence or outcome. So the results could be biased toward positive outcomes, meaning that we will need to see a strong effect for it to be believable.
   
3. This was a non-blinded diet trial without a control group. There's no way to know how much of the effect was due to avoiding gluten per se, how much was due to overall changes in diet patterns, and how much was a placebo effect.
   

With that in mind, what can we take from the survey data? I feel that we can use it to answer the following question: "what is likely to happen when a motivated, health-conscious person decides to avoid gluten for a month?" And I think we can also use it to generate (but not test) hypotheses about the effects of eating gluten on the general population.

INTERMITTENT ANDROGEN SUPPRESSION AS EFFECTIVE AS CONTINUOUS TREATMENT FOR PROSTATE CANCER

Intergroup trial shows that intermittent androgen suppression is non-inferior to continuous androgen deprivation in men with PSA recurrence after radical therapy

In men with PSA recurrence after radical radiotherapy, intermittent androgen suppression has been suggested by phase II trials to improve quality of life (QoL) but effects on survival were unknown. In the NCIC CTG PR.7/SWOG JPR.7/CTSU JPR.7/UK intercontinental CRUKE/01/013 randomized phase III trial, investigators compared intermittent androgen suppression vs continuous androgen deprivation to test for non-inferiority with respect to overall survival.

Eligible men had rising PSA > 3.0 ng/ml more than one year after radical radiotherapy, either initial or salvage, for localized prostate cancer. Patients could receive up to 1 year of neo/adjuvant androgen deprivation therapy. Stratification factors were time since radical radiotherapy, initial PSA, prior radical prostatectomy and prior androgen deprivation therapy. Intermittent androgen suppression was delivered for 8 months in each cycle with restart when PSA reached >10 ng/ml off treatment. Primary endpoint was overall survival; secondary endpoints included time to hormone refractory state, QoL, cholesterol/HDL/LDL, duration of treatment/non-treatment intervals, time to testosterone and potency recovery. The independent Data and Safety Monitoring Committee recommended halting the trial after a planned interim analysis demonstrated that a pre-specified stopping boundary for non-inferiority was crossed.

Investigators randomized 1,386 patients, 690 to intermittent and 696 to continuous androgen deprivation. Arms were balanced for important baseline factors. Median follow up was 6.9 years. Intermittent androgen suppression patients completed a median of 2 x 8 month cycles. A total of 524 deaths were observed (268 on intermittent vs 256 on continuous androgen deprivation). Median overall survival was 8.8 vs 9.1 years on intermittent and continuous androgen deprivation arms, respectively (p=0.009). The intermittent androgen suppression arm had more disease related (122 vs 97) and fewer unrelated (134 vs 146) deaths. Time to the hormone refractory state was statistically significantly improved on the intermittent androgen suppression arm (p=0.024). Intermittent androgen suppression patients had reduced hot flashes, but otherwise there was no evidence of differences in adverse events, including myocardial events or osteoporotic fractures.

The authors, who presented results at the fourth annual Genitourinary Cancers Symposium (17-19 February 2011, Orlando, USA), concluded that in men with PSA recurrence after radical radiotherapy, intermittent androgen suppression, given as described herein, is non-inferior to continuous androgen deprivation with respect to the overall survival.

The Genitourinary Cancers Symposium was co-sponsored by the American Society of Clinical Oncology, the American Society for Radiation Oncology and the Society of Urologic Oncology.

Flu Season is Here

I've noticed everyone around me getting sick lately (I seem to have become mostly immune to colds and the flu in the last couple of years), so I took a look at Google Flu Trends. Lo and behold, the United States is currently near peak flu incidence for the 2010-2011 season. Here's a graph from Flu Trends. This year's trend is in dark blue:


Flu Trends also has data for individual US states and a number of other countries.

It's time to tighten up your diet and lifestyle if you want to avoid the flu this year. Personally, I feel that eating well, managing stress effectively, and taking 2,000 IU of vitamin D3 per day in winter have helped me avoid colds and the flu.

5 health reasons to not quit coffee

By Kerri-Ann Jennings, M.S., R.D., Associate Nutrition Editor atEatingWell Magazine

I really like coffee. The morning ritual of brewing a cup, the smell that perks me up before I take a sip and, of course, the flavor all make it my favorite beverage aside from water (water’s delicious!). As a registered dietitian and a nutrition editor for EatingWell Magazine, I know that coffee is fine in moderation. It has lots of antioxidants and is low in calories if you don’t load it up with cream and sugar. Nonetheless, I always feel slightly guilty about drinking it—you know, in a “it’s so good, it must be bad” kind of way.

Don’t Miss: 5 “Bad” Foods You Should Be Eating

Which is why I’m always delighted to hear of new reasons that coffee is good for your health...and there are plenty! Over 18,000 studies on coffee have been published in the past few decades, revealing these benefits, many of which Joyce Hendley wrote about in the March/April issue of EatingWell Magazine:

Recipes to Try: Hot Fudge Pudding Cake and Other Coffee-Infused Recipes
Don’t Miss: How to Brew a “Greener” Cup of Coffee

1. It protects your heart: Moderate coffee drinkers (1 to 3 cups/day) have lower rates of stroke than noncoffee drinkers, an effect linked to coffee’s antioxidants. Coffee has more antioxidants per serving than blueberries, making it the biggest source of antioxidants in American diets. All those antioxidants may help suppress the damaging effect of inflammation on arteries. Immediately after drinking it, coffee raises your blood pressure and heart rate, but over the long term, it actually may lower blood pressure as coffee’s antioxidants activate nitric acid, widening blood vessels.

2. It diverts diabetes: Those antioxidants (chlorogenic acid and quinides, specifically) play another role: boosting your cells’ sensitivity to insulin, which helps regulate blood sugar. In fact, people who drink 4 or more cups of coffee each day may have a lower risk of developing type 2 diabetes, according to some studies. Other studies have shown that caffeine can blunt the insulin-sensitivity boost, so if you do drink several cups a day, try mixing in decaf occasionally.

Must-Read: 4 Diet-Busting Coffee-Shop Drinks (and What to Drink Instead)

3. Your liver loves it: OK, so the research here is limited, but it looks like the more coffee people drink, the lower their incidence of cirrhosis and other liver diseases. One analysis of nine studies found that every 2-cup increase in daily coffee intake reduced liver cancer risk by 43 percent. Again, it’s those antioxidants—chlorogenic and caffeic acids—and caffeine that might prevent liver inflammation and inhibit cancer cells.

4. It boosts your brain power: Drinking between 1 and 5 cups a day (admittedly a big range) may help reduce risk of dementia and Alzheimer’s disease, as well as Parkinson’s disease, studies suggest. Those antioxidants may ward off brain cell damage and help the neurotransmitters involved in cognitive function to work better.

5. It helps your headaches: And not just the withdrawal headaches caused by skipping your daily dose of caffeine! Studies show that 200 milligrams of caffeine—about the amount in 16 ounces of brewed coffee—provides relief from headaches, including migraines. Exactly how caffeine relieves headaches isn’t clear. But scientists do know that caffeine boosts the activity of brain cells, causing surrounding blood vessels to constrict. One theory is that this constriction helps to relieve the pressure that causes the pain, says Robert Shapiro, M.D., Ph.D., associate professor of neurology and director of the Headache Clinic at the University of Vermont Medical School.

Now, that’s not to say that coffee doesn’t have any pitfalls—it does. Some people are super-sensitive to caffeine and get jittery or anxious after drinking coffee; habitual coffee drinkers usually develop a tolerance to caffeine that eliminates this problem (but they then need the caffeine to be alert and ward off withdrawal headaches). Coffee can also disturb sleep, especially as people age. Cutting some of the caffeine and drinking it earlier in the day can curb this effect. Lastly, unfiltered coffee (like that made with a French press) can raise LDL cholesterol, so use a filter for heart health.

But if you like coffee and you can tolerate it well, enjoy it...without the guilt.

ENDOMETRIAL CANCER SURVIVAL BETTER UNDER SPECIAL CARE

Women with high-risk endometrial cancer who were treated by gynecological oncologists had significantly better survival than patients not receiving such care, but the same study found that in the United States, only about 20% of women with endometrial cancer are treated by these specialists.
The findings are published online in the Journal of Clinical Oncology.
"The survival benefit associated with care by a gynecologic oncologist may be explained by their better understanding of the disease process, resulting in more accurate staging, followed by adjuvant treatment if indicated," the authors explain. However, they and an outside commentator point out that the superior survival could be attributed to a "stage migration" effect.
Deaths Are Increasing
The study is important, say the researchers, because the number of annual deaths from endometrial cancer has doubled over the past 20 years.
As far as they are aware, it is the first large population-based study to evaluate the influence of subspecialty care on patients with endometrial cancer.
The team, led by John Chan, MD, from the University of California San Francisco, analyzed data on 18,338 women with endometrial cancer from 1988 to 2005, obtained from the Medicare and Surveillance, Epidemiology and End Results (SEER) database.
They found that 21.4% of these women received care from gynecologic oncologists.
Compared with the remaining women, the women who received care from gynecologic oncologists were older, had more lymph nodes removed, presented with more advanced cancer (stages III to IV), had higher-grade tumors, and were more likely to receive chemotherapy for advanced disease.
They were also more likely to undergo staging procedures with lymph node assessment and to receive chemotherapy.
They showed significantly better survival rates for high-risk disease.
For women with stage II to IV disease who received care from a gynecologic oncologist, 5-year disease-specific survival was 79%, compared with 73% for women who didn't receive such care (P = .001). The difference was even greater for women with advanced-stage disease (stage III to IV), where the 5-year disease-specific survival was 72%, compared with 64% (P < .001).
However, there was no difference in survival rates for women with early, stage I and grade 1 cancers. All of them had "excellent" overall survival, the researchers note, with a 5-year disease-specific survival of 95%.
"This is an important paper, as it suggests that patients with more advanced endometrial cancer who are managed by gynecologic oncologists experience a superior outcome," said Maurie Markman MD, vice president of patient care services and national director for medical oncology at Cancer Treatment Centers for America, in Philadelphia, Pennsylvania.
"However, one must be cautious in the interpretation of the data, as 'stage migration' may be playing an important role," Dr. Markman added. This would have the effect of making it appear that patients with more advanced disease have a superior outcome when managed by a gynecologic oncologist, when in fact it is possible that the process of being seen by a gynecologic oncologist and undergoing a more extensive staging procedure results in patients being upstaged (e.g., from stage I to stage II or stage II to stage III), he explained.
The authors concur. In a subset analysis, they found that after adjusting for the effect of surgical staging in women with stage III disease, care by a gynecologic oncologist was no longer associated with an improvement in survival (84.6% vs 84.4%; P = .6).
"The result of this subset analysis suggests that the effect of gynecologic oncologist care may be partially attributed to the comprehensive staging procedures and subsequent guidance to appropriate therapy for improving survival," they write.
However, for women with stage III to IV disease, the benefit of gynecologic oncologist care might be associated not only with comprehensive surgical staging, but also with cytoreduction of metastatic disease, Dr. Chan and colleagues note. They found that, in a subset of 1689 stage IV patients, care from a gynecologic oncologist improved survival from 52% to 63%, suggesting that cytoreductive surgery might play a role in the survival advantage.
Another factor that might be at play is that care by a gynecologic oncologist might be associated with better screening and early detection of other malignancies, the authors suggest. They cite a previous study (Am J Obstet Gynecol. 2008;198:86.e1-86.e8), which found that patients with endometrial cancer who were cared for by gynecologic oncologists were more likely to receive mammography and colorectal cancer screening, compared with a matched group of women with no history of cancer cared for by primary care providers.
The authors have disclosed no relevant financial relationships. Dr. Markman reports serving as a director, officer, partner, employee, advisor, consultant, or trustee for Boehringer Ingelheim Pharmaceuticals, Genentech, Amgen, Celgene, and Hana Biosciences; and a as speaker or a member of a speakers bureau for Eli Lilly.

Gluten-Free January Raffle Winners Selected!

Raffle winners have been selected and shirts are on their way. You know who you are. Thanks to everyone who participated and filled out the survey! For those who didn't, there's always next year.

Janine Jagger, Matt Lentzner and I are busy crunching the mountain of data we collected from the GFJ survey. We got 279 responses, which is remarkable for a survey of this nature.

Stay tuned for data!

DENOSUMAB FOR BONE METASTASES

Randomized, Double-Blind Study of Denosumab Versus Zoledronic Acid in the Treatment of Bone Metastases in Patients With Advanced Cancer (Excluding Breast and Prostate Cancer) or Multiple Myeloma.

Henry DH, Costa L, Goldwasser F, Hirsh V, Hungria V, Prausova J, Scagliotti GV, Sleeboom H, Spencer A, Vadhan-Raj S, von Moos R, Willenbacher W, Woll PJ, Wang J, Jiang Q, Jun S, Dansey R, Yeh H.

Joan Karnell Cancer Center, Philadelphia, PA; Hospital de Santa Maria and Instituto de Medicina Molecular, Lisboa, Portugal; Teaching Hospital Cochin, Paris, France; McGill University Health Centre, Montreal, Canada; Irmandade da Santa Casa de Misericordia de Sao Paulo, Sao Paulo, Brazil; University Hospital Motol, Prague, Czech Republic; University of Torino, Orbassano, Italy; HagaZiekenhuis-Leyenburg, Den Haag, the Netherlands; The Alfred Hospital, Melbourne, Australia; MD Anderson Cancer Center, Houston, TX; Kantonsspital Graubünden, Chur, Switzerland; Medical University of Innsbruck, Innsbruck, Austria; Weston Park Hospital, University of Sheffield, Sheffield, United Kingdom; and Amgen, Thousand Oaks, CA.

Abstract

PURPOSE This study compared denosumab, a fully human monoclonal anti-receptor activator of nuclear factor kappa-B ligand antibody, with zoledronic acid (ZA) for delaying or preventing skeletal-related events (SRE) in patients with advanced cancer and bone metastases (excluding breast and prostate) or myeloma. PATIENTS AND METHODS Eligible patients were randomly assigned in a double-blind, double-dummy design to receive monthly subcutaneous denosumab 120 mg (n = 886) or intravenous ZA 4 mg (dose adjusted for renal impairment; n = 890). Daily supplemental calcium and vitamin D were strongly recommended. The primary end point was time to first on-study SRE (pathologic fracture, radiation or surgery to bone, or spinal cord compression). Results Denosumab was noninferior to ZA in delaying time to first on-study SRE (hazard ratio, 0.84; 95% CI, 0.71 to 0.98; P = .0007). Although directionally favorable, denosumab was not statistically superior to ZA in delaying time to first on-study SRE (P = .03 unadjusted; P = .06 adjusted for multiplicity) or time to first-and-subsequent (multiple) SRE (rate ratio, 0.90; 95% CI, 0.77 to 1.04; P = .14). Overall survival and disease progression were similar between groups. Hypocalcemia occurred more frequently with denosumab. Osteonecrosis of the jaw occurred at similarly low rates in both groups. Acute-phase reactions after the first dose occurred more frequently with ZA, as did renal adverse events and elevations in serum creatinine based on National Cancer Institute Common Toxicity Criteria for Adverse Events grading. CONCLUSION Denosumab was noninferior (trending to superiority) to ZA in preventing or delaying first on-study SRE in patients with advanced cancer metastatic to bone or myeloma. Denosumab represents a potential novel treatment option with the convenience of subcutaneous administration and no requirement for renal monitoring or dose adjustment.

Oltipraz

Oltipraz is a drug that was originally used to treat intestinal worms. It was later found to prevent a broad variety of cancers (1). This was attributed to its ability to upregulate cellular detoxification and repair mechanisms.

Researchers eventually discovered that oltipraz acts by activating Nrf2, the same transcription factor activated by ionizing radiation and polyphenols (2, 3, 4). Nrf2 activation mounts a broad cellular protective response that appears to reduce the risk of multiple health problems.

A recent paper in Diabetologia illustrates this (5). Investigators put mice on a long-term refined high-fat diet, with or without oltipraz. These carefully crafted diets are very unhealthy indeed, and when fed to rodents they rapidly induce fat gain and something that looks similar to human metabolic syndrome (insulin resistance, abdominal adiposity, blood lipid disturbances). Adding oltipraz to the diet prevented the fat gain, insulin resistance and inflammatory changes that occurred in the refined high-fat diet group.

The difference in fasting insulin was remarkable. The mice taking oltipraz had 1/7 the fasting insulin of the refined high-fat diet comparison group, and 1/3 the fasting insulin of the low-fat comparison group! Yet their glucose tolerance was normal, indicating that they were not low on insulin due to pancreatic damage. The low-fat diet they used in this study was also refined, which is why the two control groups (high-fat and low-fat) didn't diverge more in body fatness and other parameters. If they had used a group fed unrefined rodent chow as the comparator, the differences between groups would have been larger.

This shows that in addition to preventing cancer, Nrf2 activation can attenuate the metabolic damage caused by an unhealthy diet in rodents. Oltipraz illustrates the power of the cellular hormesis response. We can exploit this pathway naturally using polyphenols and other chemicals found in whole plant foods.