Monthly Archives: February 2014

Controversial Study on Testosterone Risk Rebutted!

Controversial Study on Testosterone Risk Rebutted!
After posting the recent study concerning the risks of testosterone therapy, other authors have had the time to review that first research – I enclose a letter to the editor regarding the first study for your full reading pleasure.Dear Editor,

To anyone familiar with the testosterone field, the results reported by Vigen et al1were surprising, alleging increased deaths and cardiovascular events in a group of VA men receiving testosterone following coronary angiography, contradicting a rich literature spanning 20+ years.2   Should testosterone therapy be considered unsafe based on this article? The short answer is no. This was not a straightforward two-group comparison in which events were higher in men who received testosterone. Rather, this was a complex retrospective study with a messy dataset, containing a fatal flaw that distorted the conclusion.

The authors wrote, “The absolute rate of events were 19.9% in the no testosterone therapy group vs 25.7% in the testosterone therapy group” at 3y following angiography. This is impossible since the raw rate of events in the T group was only 10.1% (123 events in 1223 men) , compared with 21.2% (1587 events in 7486 men) in the no-T group.  The authors never acknowledge  these data  favoring the T group,  nor do they explain what drove results to an opposite conclusion.  We assume the disparity is derived from calculated estimates based on statistical adjustment for >50 variables, thus magnifying potential errors.

Both groups began as a single population, with men joining the T-group as they began treatment, thus contributing to both event curves. An MI was attributed to the T group if a man filled his testosterone prescription the same day, but to the no-T group if he hadn’t yet filled it. Attempts to glean clarity from chaos using statistics is laudable, yet as anyone with a teenager knows, there is a large difference between what is expected and what actually occurs.

Basic information is not provided. Did time-zero begin for T-group at angiography or testosterone initiation?  Raw event data for years 1-3?  Mean time to events after testosterone? Person-years of exposure for both groups?

Our greatest concern is that 1132 men with MI or stroke who subsequently received testosterone were incorrectly excluded from the study. It was irrelevant what happened after their event. All these events occurred in the no-T group, increasing its number of events by 71%, thereby yielding an outcome consistent with two recent studies demonstrating a substantial reduction in mortality with testosterone therapy.3,4

Abraham Morgentaler, MD, Abdulmaged Traish, PhD  Ravi Kacker, MD

References

1. Vigen R, O’Donnell CI, Baron AE, et al. Association of testosterone therapy with mortality, myocardial infarction, and stroke in men with low testosterone levels. JAMA 2013 ; 310:1829-36.

2. Traish AM, Miner MM, Morgentaler A, Zitzmann M. Testosterone deficiency. Am J Med 2011; 123:578-87.

3. Shores MM, Smith NL, Forsberg CW, Anawalt BD, Matsumoto AM. Testosterone treatment and mortality in men with low testosterone levels. J Clin Endocrin Metab 2012 ; 97:2050-8.

4. Muraleedharan V, Marsh H, Kapoor D, Channers KS, Jones TH. Testosterone deficiency is associated with increased risk of mortality and testosterone replacement improves survival in men with type 2 diabetes. Eur J Endocrin 2013; 169:725-33.

WWW.  What will Work for Me.  I smell a rat.  I’ve seen this happen enough times before.  I would suggest that the publicity arm of some big pharmaceutical company put together this rather awful study, and then made sure it hit the major news media and was widely published to sow fear and anxiety about the use of testosterone in men.  We will never know, but it’s nice to hear one of the major gurus on testosterone therapy reply with such a thoughtful and insightful critique of the first study.

POP QUIZ

1.   The language in the rebuttal letter to the editor is in clear English that you can understand.  T or F

False.  Even I can’t read it.

2.  It appears that there were conclusions drawn that reflected a bias on the part of the researchers.  T or F

That’s what I take away from it.  They had an axe to grind.

3.    Morgenthaler’s reading of the same data appears to show a positive and helpful bias towards the use of testosterone.  T or F

True

4.  The fatal flaw of the study was that men who had had a heart attack or stroke but received testosterone were excluded, and should not have been.  T or F

That’s it.

5.  Do you end up confused?

Yes.  It’s exactly what publications like this are intended to do.

ANTIOXIDANTS ACCELERATE LUNG CANCER IN MICE

Antioxidants Accelerate Lung Cancer In Mice
Reference:  Science Translational Medicine Jan 2014It was a huge disappointment in the 1990s when we found that Vitamin E and A seemed to increase the rate of cancer growth in smokers.  Millions of Americans had been taking those two anti-oxidants, and then stopped!  Why would something so seemingly beneficial cause harm?   Until now, no-one has followed up on these observations and tried to nail down the reasons.  That’s what this Swedish team did in this study.  Back to the drawing board with mice with a study that investigates just why antioxidants accelerate lung cancer.

What do anti-oxidants do?  Our body is constantly generating “reactive oxygen species”, or ROS.  These come from eating high sugar containing foods, or smoking, or eating grilled meats…many causes.  But ROS damage cellular structures all over your body.  We have all sorts of internal mechanisms that generate our own natural anti-oxidants to protect us.  It seems only natural that taking a little extra would help protect us even more, especially considering that those compounds themselves protect us naturally when in normal proportions.

What Martin Bergo’s team found was that Vitamin E and N-acetyl cysteine did extinguish ROS in normal cells and in cancer cells.  Cancer cells were found to have low levels of ROS, and these two anti-oxidants lowered them even further.  And then something interesting happened.  Using doses that would mimic what happens to humans taking a vitamin pill, the anti-oxidants protected the cancer cells from DNA damage.  That allowed the cancer cells to then grow faster, larger and to kill their hosts even faster.  Hmmm.  And inside the study, they also found that the anti-oxidants dramatically reduced the activity of p53, a guardian protein that prevents cancer by dectecting damaged DNA and slowing down cell division.

Fair enough.  This explains what we have observed in humans.  From the New England Journal Article back in 1994 on Vitamin E to the Cochrane Review in 2012 that review 78 studies in humans, anti-oxidants have not been shown to improve survival in humans.  The suppression of that p53 gene is real and may be the key.  It is typically suppressed in late stage cancer, when cancer really takes off.  Anti-oxidants suppressing that gene may be the key to why this happens.

There still may be rational explanation we haven’t parsed out yet.  There are 8 Vitamin Es – to take one, alpha-tocopherol, and give it in high doses excludes the others.  Most foods contain many of them.  Same thing with Vitamin A.  There are lots of carotenoids.  Whole foods contain them all, not one in isolation.  And they have been proven to be vital for many biological functions.   What’s a caring, thoughtful, health conscious person to do?

WWW. What will work for me.  Science is messy.   If I were a high risk for cancer, I would not take Vit E or A.  I may very likely have a small cancer and taking these supplements might accelerate those diseases.  Cancer is not normal humans though.  If I’m low risk for lung cancer (non-smoker) the story may still have more chapters to go.  I’m still not taking extra E or A.

Pop Quiz
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1.   Vitamin E, in normal supplemen doses, accelerates the speed of implanted lung cancer in mice.  T or FYup. That’s what this study shows.2.  The p53 gene helps protect normal cells from cancers, but in cancer cells seems to be suppressed and allows the cancer cell to take off and grow faster.  T or FTrue

3.   Our bodies have natural systems that neutralize reactive oxygen species.  T or  F

True.

4.  So explain why taking extra anti-oxidants  makes you worse off!

Can’t.  Have to wait for more science.  It’s utterly confounding.

Suggest you eat whole food, grown locally with the least amount of chemicals you can find.

 

Non Celiac Wheat Sensitivity Arrives

Non-Celiac Wheat Sensitivity Arrives
 Reference:  Scientific American  Feb 2014, British Medical JournalEveryone knows about gluten sensitivity these days.  It’s sort of the rage.  Gluten free this and that is showing up on menus.  I got a gluten free hamburger at a restaurant (just a naked hamburger and a slice of tomato.  No bun).  Churches have gluten free communion bread.  Breweries are turning out gluten free beer.  But you may not get an understanding nod from your doctor if you say you feel better when you don’t eat wheat.  You get your celiac disease blood test and come back negative.  What next?  Even Scientific American published an article last year poo-pooing the gluten free craze.

Measurement helps.  Wheat turns out to be an interesting grain.  With the combination of three grains that were combined back in the 1950s to make our modern strains of wheat, we added 28 more chromosomes to the 14 original chromosomes.  Modern humans have about 20,000 genes.  Modern wheat has 95,000.   When we eat wheat, we may not always have a friendly reaction.  And sorting out 95,000 genetic messages might take science a while.  If we just look at gluten, we might be missing the real story.  We know that gluten is the sticky stuff that allows wheat to rise because it helps make the yeast bubbles.  It also has several segments that are quite distinct and cause separate immune reactions.  But are there other proteins in wheat that may be raising the ruckus?  Or is it a different type of immune reaction that we have not measured to date?

Celiac disease is certainly a distinct entity.  We can measure IgE antibodies to gluten and we can biopsy the small bowel and show stunted little villi in the wall of the bowel. That makes for blood tests that are negative or positive.  A biopsy of the wall of your small bowel will be positive for those villi.  You got a genuine diagnosis.  But what happens if your body makes IgG?

Well, along come Non-Celiac Wheat Sensitivity Syndrome.  It has now been recognized as a distinct entity by the Celiac Disease association.  And better, a company by the name of Cyrex has developed an immune assay that can measure 24 different immune reactions in which gluten and wheat might be causing trouble.   Check our their “Array 3” with all its complicated names.   The key concept here is that for every IgE test, the kind that develops with allergy, they also have an IgG test.   Those folks who have the “Non-celiac” wheat sensitivity will have positive IgG tests, and their IgE will be negative.  In a traditional health setting, they will be told their gluten testing is all negative.  They will feel that their problem must be in their heads.  But they don’t feel well when they eat wheat.

Suddenly it makes sense, and we have a test to objectify it.  IgG may not make for the dramatic symptoms of IgE, but the low grade, chronic inflammation it sets off just may be the key to understanding heart disease, Alzheimer’s…..this may be huge!

WWW.  What will work for me.  Wow.  I’ve now measured five people in my practice and it works!  It’s real. The Cyrex array finds folks with negative celiac testing, but who have symptoms.  I’m totally fascinated.  This is a story to follow.   This might be something I test myself for!

POP QUIZ

1.  Gluten sensitivity with celiac disease is rare – about 1 in 138 people.  T or F

True

2.   People can be wheat sensitive and have negative celiac disease tests.  T or F

True

3.   To date, traditional medicine has called these folks “nuts”.  T or F

True

4.   Wheat has more genes in it than humans.  T or F

Yup. Some 4 times.

5.   The immune system can find tiny amounts of material and make immune reactions to it.  T or F

Tiny is hardly the word.  That’s how it protects us.

6.  The Cyrex company has figured out a way to test for non-gluten wheat sensitivity that may answer the key question, “Why do I feel crummy when I eat wheat?”

That’s it in a nutshell. Stay tuned.

Find me a Cold Spot for Depression

Find Me a Cold  Spot for Depression

Reference  The Jungle Effect by Daphne Miller

It’s February in just about the coldest winter in decades.  We’ve been cooped up forever and are all just feeling strung out.  The “mid winter blahs” are upon all of us.  You wouldn’t be faulted to claiming yourself to be a bit depressed.  Then, would it surprise you if I told you that Iceland, much further north, much darker and more dreary in winter, is a “cold spot” for depression, meaning it has less than half the depression of much of the rest of the world?   I would think they would all be grabbing tickets for Cancun.   Not so.  Those cheerful Icelanders seem to do just fine in winter and have a sunny attitude about it.  They aren’t depressed.   How!

Now, an interesting aside is that a whole bunch of Icelanders immigrated to Canada in the first part of the last century and set up shop in places like Gimli, Manitoba.  What happened to them there?  They got depressed in winter, just like the local Canadians of Scotch Irish descent.  It’s not their genes, it’s the environment of Iceland.  The immigrants lost the environmental effects of food and started eating a Canadian diet.

Alright, research the environment of Iceland and what do you find?   Everyone eats fish.  Lots of fish.  Every day, every meal. Fish.  Fresh caught, north Atlantic Char, cod, salmon, herring.  And measure their blood levels of omega three fatty acids and what do you find?  Their levels of omega threes are on the order of three times ours here in North America.   And Hibblen studied fish consumption by nation and found as much as a 60 fold variation from nation to nation, all tied to the amount of fish they ate.

Is fish the only reason they have less depression in Iceland?  There are parts of Iceland that don’t eat fish and eat virtually nothing but lamb.   Again, review of their lamb shows that it is raised on Icelandic moss pastures and has some of the highest omega-3 fat contents found in red meat animals.  Their lambs aren’t fed on corn and beans, which flush out the omega threes – but rather dowdy, ordinary local potent moss.   The cows eat that too.  Guess what their mild contains?  You got it.  Milk in Iceland is loaded with omega-3 fats.

Your brain is loaded with omega-3 fats.  Our American diet has had a dramatic loss of omega-3s as our animals have been raised on corn and beans (no omega threes) instead of grass.  The hottest topic in psychiatry now is that depression is an inflammatory disease.  Omega-three fats are the precursors to making anti-inflammatory eicosinoids.  AKA: turn off depression.   We are able to measure the American brain containing less omega-3s than it used to.  And we know our food has changed.  The question remains, does bringing the food back reduce the depression?

WWW. What will work for me?  Well, I certainly have found I make it through winter easier when I have some Vitamin D.  But I started taking fish oil the same time.  Which was it?  I’m determined to up my intake a bit more.  Two grams a day of DHA and EPA is what a teaspoon of liquid provides.  That’s still less than 2 oz a day of salmon.  Piddling little dose for those Icelanders.  8 oz of liquid D a day for a month would be a better trial!

Pop Quiz
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1.  Depression has similar rates all around the world?  T or FDramatically false. Some societies have much lower rates.

2.   Iceland is one of the world’s “Cold Spots” meaning it has much less depression than other places?
T or F

True

3.   Icelanders, who immigrated to Canada still have little depression?  T or F

False. They have the same rates as the Canadians around them, despite living in a similar winter climate to Iceland.  Major difference, they eat much less fish.

4.   Icelanders eat fish day in and day out, and most of it is fresh, ocean fish with abundant EPA and DHA content.   T or F

True

5.   Icelanders have higher blood levels of DHA and EPA than we do in North America.  T or F

Almost triple.

6.   Fish oil (DHA and EPA) is a criical ingredient in your brain, comprising as much as 40% of the dry weight of your brain.  T or F

Wow. True

7.   DHA is the precursor molecule for your body to make anti-inflammatory messages in your body?  T or F

True

8.  Depression may be considered an inflammatory disease of the brain?  T or F

Just go to any recent American Society of Psychiatry Meeting

9.  You can get good DHA and EPA from Grass Raised lamb or grass raised dairy cow? T or F

True on both accounts.