Thursday, September 30, 2010

Association of Vitamin D Status with Serum Androgen Levels in Men

From Clinical Endocrinology

E. Wehr; S. Pilz; B. O. Boehm; W. März; B. Obermayer-Pietsch


Studies in rodents indicate a role of vitamin D in male reproduction, but the relationship between vitamin D and androgen levels in men is largely unexplored. We aimed to investigate the association of 25-hydroxyvitamin D [25(OH)D] levels with testosterone, free androgen index (FAI) and SHBG. Moreover, we examined whether androgen levels show a similar seasonal variation to 25(OH)D.

In this cross-sectional study, 25(OH)D, testosterone and SHBG levels were assessed by immunoassay in 2299 men who were routinely referred for coronary angiography (1997–2000).

Main outcome measures were associations of 25(OH)D levels with testosterone, SHBG and FAI. FAI was calculated as testosterone (nmol/l)/SHBG (nmol/l) × 100.
Results Men with sufficient 25(OH)D levels (≥30 μg/l) had significantly higher levels of testosterone and FAI and significantly lower levels of SHBG when compared to 25(OH)D insufficient (20–29·9 μg/l) and 25(OH)D-deficient (<20 μg/l) men (P < 0·05 for all). In linear regression analyses adjusted for possible confounders, we found significant associations of 25(OH)D levels with testosterone, FAI and SHBG levels (P < 0·05 for all). 25(OH)D, testosterone and FAI levels followed a similar seasonal pattern with a nadir in March (12·2 μg/l, 15·9 nmol/l and 40·8, respectively) and peak levels in August (23·4 μg/l, 18·7 nmol/l and 49·7, respectively) (P < 0·05 for all).

Androgen levels and 25(OH)D levels are associated in men and reveal a concordant seasonal variation. Randomized controlled trials are warranted to evaluate the effect of vitamin D supplementation on androgen levels.

It is Not Only Cars That Deserve Good Maintenance: Brain Care 101

Jan 11, 2008
By: Alvaro Fernandez

Last week, the US Car Care Coun­cil released a list of tips on how to take care of your car and “save big money at the pump in 2008.”

You may not have paid much atten­tion to this announce­ment. Yes, it’s impor­tant to save gas these days; but, it’s not big news that good main­te­nance habits will improve the per­for­mance of a car, and extend its life.

If we can all agree on the impor­tance of main­tain­ing our cars that get us around town, what about main­tain­ing our brains sit­ting behind the wheel?

A spate of recent news cov­er­age on brain fit­ness and “brain train­ing” has missed an impor­tant con­stituency: younger peo­ple.
Recent advance­ments in brain sci­ence have as tremen­dous impli­ca­tions for teenagers and adults of all ages as they do for seniors.

In a recent con­ver­sa­tion with neu­ro­sci­en­tist Yaakov Stern of Colum­bia Uni­ver­sity, he related how sur­prised he was when, years ago, a reporter from Sev­en­teen mag­a­zine requested an inter­view. The reporter told Dr. Stern that he wanted to write an arti­cle to moti­vate kids to stay in school and not to drop out, in order to start build­ing their Cog­ni­tive Reserve early and age more gracefully.

What is the Cog­ni­tive Reserve?

Emerg­ing research since the 90s from the past decade shows that indi­vid­u­als who lead men­tally stim­u­lat­ing lives, through their edu­ca­tion, their jobs, and also their hob­bies, build a “Cog­ni­tive Reserve” in their brains. Only a few weeks ago another study rein­forced the value of intel­lec­tu­aly demand­ing jobs.

Stim­u­lat­ing the brain can lit­er­ally gen­er­ate new neu­rons and strengthen their con­nec­tions which results in bet­ter brain per­for­mance and in hav­ing a lower risk of devel­op­ing Alzheimer’s symp­toms.
Stud­ies sug­gest that peo­ple who exer­cise their men­tal mus­cles through­out their lives have a 35–40% less risk of man­i­fest­ing Alzheimer’s.

As astound­ing as these insights may be, most Amer­i­cans still devote more time to chang­ing the oil, tak­ing a car to a mechanic, or wash­ing it, than think­ing about how to main­tain, if not improve, their brain performance.

Fur­ther, bet­ter brain scan­ning tech­niques like fMRI (glos­sary) are allow­ing sci­en­tists to inves­ti­gate healthy live brains for the first time in his­tory. Two of the most impor­tant find­ings from this research are that our brains are plas­tic (mean­ing they not only cre­ate new neu­rons but also can change their struc­ture) through­out a life­time and that frontal lobes are the most plas­tic area. Frontal lobes, the part of our brains right behind the fore­head, con­trols “exec­u­tive func­tions” — which deter­mine our abil­ity to pay atten­tion, plan for the future and direct behav­ior toward achiev­ing goals. They are crit­i­cal for adapt­ing to new sit­u­a­tions. We exer­cise them best by learn­ing and mas­ter­ing new skills.

This part of the brain is del­i­cate: our frontal lobes wait until our mid to late 20s to fully mature. They are also the first part of our brain to start to decline, usu­ally by mid­dle age.

In my view, not enough young and middle-aged peo­ple are ben­e­fit­ing from this emerg­ing research, since it has been per­ceived as some­thing “for seniors.” Granted, there are still many unknowns in the world of brain fit­ness and cog­ni­tive train­ing, we need more research, bet­ter assess­ments and tools. But, this does not mean we can­not start car­ing for our brains today.

Recent stud­ies have shown a tremen­dous vari­abil­ity in how well peo­ple age and how, to a large extent, our actions influ­ence our rate of brain improve­ment and/or decline. The ear­lier we begin the bet­ter. And it is never too late.

What can we do to main­tain our brain, espe­cially the frontal lobes?
Focus on four pil­lars of brain health:
phys­i­cal exer­cise, a bal­anced diet, stress man­age­ment, and brain exer­cise. Stress man­age­ment is impor­tant since stress has been shown to actu­ally kill neu­rons and reduce the rate of cre­ation of new ones.
Brain exer­cises range from low-tech (i.e. med­i­ta­tion, mas­ter­ing new com­plex skills, life­long learn­ing and engage­ment) to high-tech (i.e. using the grow­ing num­ber of brain fit­ness soft­ware pro­grams).

I know, this is start­ing to sound like those lists we all know are good for us but we actu­ally don’t do. Let me make it eas­ier by propos­ing a new New Year Res­o­lu­tion for 2008: every time you wash your car or have it washed in 2008, ask your­self, “What have I done lately to main­tain my brain?”

Improving Memory?

Get­ting from Here to There:
Mak­ing Mem­ory Con­sol­i­da­tion Work

By Bill Klemm, Ph. D.

Until con­sol­i­da­tion has occurred, a short-term mem­ory is very vul­ner­a­ble, as all of us have expe­ri­enced from look­ing up a phone num­ber only to have some dis­trac­tion cause us to lose the num­ber before we can get it dialed.

What is “consolidation”?

Brain researchers use the term “con­sol­i­da­tion” for the process whereby short-term mem­ory gets made more permanent.

Here, I would like to dis­cuss some aspects of con­sol­i­da­tion that many peo­ple may not know about: why sleep is so impor­tant, why mem­ory must be prac­ticed, and how test­ing pro­motes consolidation.

1. Over-training: You Can Learn Too Much

Exper­i­ments have shown that human mem­ory per­for­mance unex­pect­edly dete­ri­o­rated if learn­ing ses­sions were increased to four 60-minute ses­sions at reg­u­lar inter­vals on the same day. In other words, the more the sub­jects were trained, the poorer they per­formed. How­ever, this inter­fer­ence did not occur if sub­jects were allowed to nap for 30–60 min­utes between the sec­ond and third sessions.

It is hard to explain why over-training dis­rupts per­for­mance, but I sus­pect that as train­ing tri­als are repeated the infor­ma­tion starts to inter­fere with mem­ory con­sol­i­da­tion, per­haps because of bore­dom or fatigue in the neural cir­cuits that medi­ate the learn­ing. Nap­ping must have a restora­tive func­tion that com­pen­sates for the neg­a­tive effects of over-training. What all this sug­gests is that mem­ory con­sol­i­da­tion would be opti­mized if learn­ing occurred in short ses­sions that are repeated but only with inter­ven­ing naps and on dif­fer­ent days with reg­u­lar night-time sleep. In other words, repeat­ing long study peri­ods in the same day on the same task can be counter-productive. This is yet another rea­son why stu­dents should not cram-study for exams. Learn­ing should be opti­mized by rehears­ing the same learn­ing mate­r­ial on sep­a­rate days where nor­mal sleep occurred each night.


- Maquet, P. et al. 2002. Be caught nap­ping: you’re doing more than rest­ing your eyes.Nature Neu­ro­science. 5 (7); 618–619.

- Med­nick, Sara, et al. 2002. The restora­tive effect of naps on per­cep­tual deterioration.Nature Neu­ro­science. 5 (7): 677–681.

2. Los­ing Your Past

Do you remem­ber the names of your elementary-school teach­ers? How about the name of the bully in mid­dle school? Or names of your friends when you were a kid? These are all things you remem­bered well at one time and remem­bered for a long time. But you may well have for­got­ten by now.

A recent study on rats sug­gests what it takes to sus­tain longer term mem­o­ries. Rats in the study learned a “bait shy­ness” task. Rats were given a drink of saccharin-flavored water, and then shortly after­wards injected with lithium, which made them nau­se­ated. This was a typ­i­cal con­di­tioned learn­ing sit­u­a­tion, as with Pavlov’s dogs. In this case, rats typ­i­cally remem­bered to avoid such water for many weeks. This is the basis for “bait shy­ness.” If rats sur­vive a poi­son­ing episode, they will avoid that bait in the future. In this exper­i­ment, one group of rats received an injec­tion directly into the part of the brain that holds taste mem­o­ries. This injec­tion con­tained a drug that blocks a cer­tain enzyme, a pro­tein kinase. These rats lost their learned taste aver­sion. The bad mem­ory was lost irre­spec­tive of when the injec­tion was made dur­ing the 25 days after learn­ing occurred. Giv­ing the enzyme blocker before learn­ing had no effect on learn­ing to avoid the fla­vored water. The pro­tein kinase thus seems to be nec­es­sary for sus­tain­ing a long-term mem­ory. It is pos­si­ble that other long-term mem­o­ries the rats may have had were also wiped out by the enzyme-blocking drug.

So what is the prac­ti­cal impor­tance? I sug­gest that even “long-term” mem­o­ries have to get rehearsed or they may even­tu­ally for­got­ten. Or if you do remem­ber, there is a good chance that the mem­ory is cor­rupted, that is, not totally cor­rect. The con­se­quence is that things that hap­pened long ago may be either for­got­ten, or misremembered.

What sus­tains the enzyme nec­es­sary for long-term mem­ory? I sus­pect it is rehearsal and peri­odic reac­ti­va­tion of the mem­ory. Some sci­en­tists are excited about the pos­si­bil­ity of devel­op­ing a drug to manip­u­late lev­els of the enzyme. The prob­lem with that, how­ever, is that the drug could abol­ish old mem­o­ries that you might not want to for­get (like your name) or may cause you to remem­ber too much that is now irrelevant.

Source: Shema, R., Sack­tor, T. C., and Dudai, Y. 2007. Rapid era­sure of long-term mem­ory asso­ci­a­tions in the cor­tex by an inhibitor of PKM. Sci­ence. 317:951–953.

3. Test­ing Pro­motes Consolidation

Tests do more than just mea­sure learn­ing. Tests are learn­ing events. That is, test­ing forces retrieval of incom­pletely learned mate­r­ial and that very act of retrieval is a rehearsal process that helps to make the learn­ing more per­ma­nent. Test­ing, and not actual study­ing, is the key fac­tor on whether or not learn­ing is con­sol­i­dated into longer term memory.

A recent report from Wash­ing­ton Uni­ver­sity in St. Louis, exam­ined the role that retrieval had on the abil­ity to recall that same mate­r­ial after a delay of a week. In the exper­i­ment, col­lege stu­dents were to learn a list of 40 for­eign lan­guage vocab­u­lary word pairs that were manip­u­lated so that the pairs either remained in the list (were repeat­edly stud­ied) or were dropped from the list once they were recalled. It was like study­ing flash cards: one way is to keep study­ing all the cards over and over again; the other way is to drop out a card from the stack every time you cor­rectly recalled what was on the other side of the card. After a fixed study period, stu­dents were tested over either the entire list or a par­tial list of only the pairs that had not been dropped dur­ing study. Four study and test peri­ods alter­nated back-to-back. Stu­dents were also asked to pre­dict how many pairs they would be able to remem­ber a week later, and their pre­dic­tions were com­pared with actual results on a final test a week later.

The ini­tial learn­ing took about 3–4 tri­als to mas­ter the list, and was not sig­nif­i­cantly affected by the strat­egy used (rehears­ing the entire list or drop­ping items out as they were recalled). On aver­age, the stu­dents pre­dicted that they would be able to remem­ber about half of the list on a test that was to be given a week later. How­ever, actual recall a week later var­ied con­sid­er­ably depend­ing on learn­ing con­di­tions. On the final test, stu­dents remem­bered about 80% of the word pairs if they had been tested on all the word pairs, no mat­ter whether they had been stud­ied mul­ti­ple times with all of them in the list or if they dropped cor­rectly recalled words from the list in later study tri­als. How­ever, recall was only about 30% cor­rect when cor­rectly iden­ti­fied words were dropped from sub­se­quent tests, even though all words were stud­ied repeat­edly. In other words, it was the repeated test­ing, not the study­ing, that was the key fac­tor in suc­cess­ful longer-term memory.

So, what is the prac­ti­cal appli­ca­tion? When using flash cards, for exam­ple, you need to fol­low each study ses­sion (whether or not you drop cards from the stack because you know them), with a for­mal test over all the cards. Then, repeat the process sev­eral times, with study and test epochs back-to-back. Can we extend this prin­ci­ple of fre­quent test­ing to other kinds of learn­ing strate­gies? I would guess so.

Why does forced recall, as dur­ing test­ing, pro­mote con­sol­i­da­tion? It prob­a­bly relates to other recent dis­cov­er­ies show­ing that each time some­thing is recalled the mem­ory is re-consolidated. If the same infor­ma­tion is con­sol­i­dated again and again, the mem­ory is pre­sum­ably reinforced.

This study also showed that the sub­jects could not pre­dict how well they would remem­ber, which is con­sis­tent with my 45 years expe­ri­ence as a pro­fes­sor. Stu­dents are fre­quently sur­prised to dis­cover after an exam­i­na­tion that they did not know the mate­r­ial as well as they thought they did. Tests not only reveal what they know and don’t know, but serve to increase how much they even­tu­ally learn. If I were still teach­ing, I would give more tests. And I would encour­age stu­dents to use self-testing as a rou­tine learn­ing strat­egy, some­thing that one study revealed to be a seldom-used strat­egy. The repeated self-tests should include all the study mate­r­ial and not drop out the mate­r­ial that the stu­dent thinks is already mastered.

Source: Karpicke, Jef­frey D., and Roedinger, Henry L. III. 2008. The crit­i­cal impor­tance of retrieval for learn­ing. Sci­ence. 319: 966–968.

— W. R. (Bill) Klemm, D.V.M., Ph.D. Sci­en­tist, pro­fes­sor, author, speaker As a pro­fes­sor of Neu­ro­science at Texas A&M Uni­ver­sity, Bill has taught about the brain and behav­ior at all lev­els, from fresh­men, to seniors, to grad­u­ate stu­dents to post-docs. His recent books include Thank You Brain For All You Remem­ber and

The Ten Habits of Highly Effective Brains

Aug 22, 2007
By: Alvaro Fernandez

Let’s review some good lifestyle options we can fol­low to main­tain, and improve, our vibrant brains.

1.Learn what is the “It” in “Use It or Lose It”.
A basic under­stand­ing will serve you well to appre­ci­ate your brain’s beauty as a liv­ing and constantly-developing dense for­est with bil­lions of neu­rons and synapses.
2.Take care of your nutri­tion. Did you know that the brain only weighs 2% of body mass but con­sumes over 20% of the oxy­gen and nutri­ents we intake? As a gen­eral rule, you don’t need expen­sive ultra-sophisticated nutri­tional sup­ple­ments, just make sure you don’t stuff your­self with the “bad stuff”.
3.Remem­ber that the brain is part of the body.
Things that exer­cise your body can also help sharpen your brain: phys­i­cal exer­cise enhances neurogenesis.
4.Prac­tice pos­i­tive, future-oriented thoughts until they become your default mind­set and you look for­ward to every new day in a con­struc­tive way.
Stress and anx­i­ety, no mat­ter whether induced by exter­nal events or by your own thoughts, actu­ally kills neu­rons and pre­vent the cre­ation of new ones.
You can think of chronic stress as the oppo­site of exer­cise: it pre­vents the cre­ation of new neurons.
5.Thrive on Learn­ing and Men­tal Chal­lenges. The point of hav­ing a brain is pre­cisely to learn and to adapt to chal­leng­ing new envi­ron­ments.
Once new neu­rons appear in your brain, where they stay in your brain and how long they sur­vive depends on how you use them. “Use It or Lose It” does not mean “do cross­word puz­zle num­ber 1,234,567″.
It means, “chal­lenge your brain often with fun­da­men­tally new activities”.
6.We are (as far as we know) the only self-directed organ­isms in this planet. Aim high. Once you grad­u­ate from col­lege, keep learn­ing.
The brain keeps devel­op­ing, no mat­ter your age, and it reflects what you do with it.
7.Explore, travel. Adapt­ing to new loca­tions forces you to pay more atten­tion to your envi­ron­ment. Make new deci­sions, use your brain.
8.Don’t Out­source Your Brain. Not to media per­son­al­i­ties, not to politi­cians, not to your smart neigh­bour… Make your own deci­sions, and mis­takes. And learn from them. That way, you are train­ing your brain, not your neighbour’s.
9.Develop and main­tain stim­u­lat­ing friend­ships. We are “social ani­mals”, and need social inter­ac­tion. Which, by the way, is why ‘Baby Ein­stein’ has been shown not to be the panacea for chil­dren development.
10.Laugh. Often. Espe­cially to cog­ni­tively com­plex humor, full of twists and sur­prises. Bet­ter, try to become the next Jon Stewart

Now, remem­ber that what counts is not read­ing this article-or any other-, but prac­tic­ing a bit every day until small steps snow­ball into unstop­pable, inter­nal­ized habits…so, pick your next bat­tle and try to start improv­ing at least one of these 10 habits today!

Tuesday, September 28, 2010

Should Teens Be Able to Sleep Later?

From Medscape Pediatrics > Viewpoints
William T. Basco, Jr., MD

Impact of Delaying School Start Time on Adolescent Sleep, Mood, and Behavior
Owens JA, Belon K, Moss P
Arch Pediatr Adolesc Med. 2010;164:608-614.

Study Summary
Owens and colleagues review evidence suggesting that biological changes during puberty result in adolescents shifting their sleep periods (ie, falling asleep later in the evening), but they still require the same amount of sleep (approximately 9 hours).
Many studies have shown that adolescents are generally sleep-deprived, and sleep deprivation is associated with worse academic performance.
This study was conducted in a single school that had both boarding students and day students in 9th-12th grades (total students, 357; 81.5% boarding students).
The school had historically begun morning classes at 8:00 am, but during the trial period (January and February 2009) the start time was moved to 8:30.
The evening routines for boarding students did not change during the trial period, with "lights-out" at graduated times depending on grade level.

The investigators collected self-completed survey data pre- and postintervention, including a survey of sleep habits, a survey that measured sleepiness, and another survey that assessed whether the student felt that he or she was a "morning" or "evening" person. The investigators also collected objective data on visits to the school health center, missed appointments, tardiness, and breakfast consumption.

More than 75% of the student body completed the surveys (278 students). Fifty-four percent of the students were girls, the mean age was 16.4 years, and > 80% had grades that were "B" or better.
The change in classroom start time was associated with an average increase in sleep duration of 45 minutes (95% confidence interval, 27-49). Most of the difference was accounted for by a wake time that was an average of 30 minutes later.
In addition, students went to bed an average of 18 minutes earlier. On average, even with the start-time change, 12th graders slept 40 minutes less than 9th graders.
The sleep duration of boarding students on school nights did not different significantly from that of day students.
Overall, students were much less likely to report rarely/never getting enough sleep or dissatisfaction with the amount of sleep after the time change.
The students' assessments of their own sleepiness declined after the change. Health outcomes also improved, with a reduction in the percentage of students who visited the health clinic (15.3% at first survey compared with 4.6% at second survey, P = .03).
Fewer missed morning appointments, fewer requests for late passes, and more than a 50% reduction in the percentage of students who used the health center for afternoon respite were also observed after the change in school start time.
The investigators concluded that even a modest delay in the start of the school day is associated with improved mood, health, and alertness in adolescents.

In quasi-experimental designs (ie, nonrandomized, as in this case), 1 way that investigators can make the case that the intervention was the cause of the outcome (and not just associated with it) is by finding associations between the change and multiple outcome measures.
In this case, credit goes to the investigators for adding objective outcomes, such as health center utilization, to self-assessment surveys. Looking at objective changes in grades would have been another objective measure, but this was probably precluded by the short duration of the experiment.
It is worth noting that this is an independent school population, and > 80% of the students had a structured evening routine.
It is difficult to know whether the same benefits would be accrued by students who have more varied routines or by students in other settings with more disparate economic and educational backgrounds.

Monday, September 27, 2010

Exercises to Avoid with Lower Back Pain

By: Mel Joelle

When people suffer from back pain, it seems logical to let the back take a break from activity so that it can heal properly. While this is true to an extent, too much inactivity can sometimes worsen back pain. Doctors, physical therapists, and fitness trainers often recommend exercise for back problems.
The reason that exercise is recommended for back pain sufferers is that it improves circulation to the affected back muscles, and physical activity lessens the risk of muscles tightening up in the first place. However, there are several exercises to avoid with lower back pain.

First, it helps to know the root cause of the back pain. If a specific incident is known to be the culprit, such as heavy lifting or a sudden strain while exercising, then the standard two days of rest should suffice; however,chronic back pain sufferers should always check with a doctor before attempting to perform any exercises that are meant to relieve lower back pain.

The main point to keep in mind is that any type of activity that causes pain should be stopped immediately.
The best exercises to undertake while suffering from back pain are those which do not involve excessive flexion or extension.

Those who experience lower back pain should not be involved in any team or contact sports (such as baseball, football, or basketball) until they feel better. While the cardiovascular activity will certainly help the back in terms of improved circulation, there is no guarantee that another player wont collide and worsen a back injury.
Other exercises to avoid with lower back pain involve sudden movements, such as golfing or gymnastics.

Cycling should be avoided if done for recreational purposes, so those who rely on a bicycle for transportation should only travel as much as necessary and keep at a slow, steady pace.
Running should be avoided altogether, since the jarring motion can have an adverse effect on the back.
Walking should substitute it for a few days while the back heals, or low impact machines like a stair climber or stationary bike can be used with proper posture.
Swimming is also better on the joints than just about any exercise; while it provides plenty of resistance; it also reduces the strain of weight.

Some strength training exercises are also off-limits, including sit-ups and leg raises. Both of these exercises use the lower back extensively, and often, those who are not experienced with these exercises do them incorrectly.

Many fitness trainers recommend Pilates, which is designed to stretch out the muscles and promote proper alignment of the spine.
While Pilates is an effective way to improve circulation and alignment, it can exacerbate back problems if done improperly.

There are a few guidelines on which specific exercises to avoid with lower back pain, but the general idea is to listen to the body and refrain from overexertion.
Exercise is supposed to make one feel challenged but not leave him or her in pain.
Low-impact cardiovascular activity combined with light stretching can help relieve back problems, and in time can help improve ones health overall.

Click here to read the rest of Lower Back Pain. If you enjoyed this article, you also might like our other stories about Back Pain Exercises.

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Sunday, September 26, 2010

Lower Folate Levels Increase Risk for Depressive Symptoms, Particularly in Women

From Medscape Medical News

Caroline Cassels

September 24, 2010 — Lower serum folate levels appear to be associated with an increased risk for depressive symptoms, a large population-based, cross-sectional study suggests.

Data on US adults from the National Health and Nutrition Examination Survey (NHANES) show elevated depressive symptoms were inversely associated with folate status, particularly among women.

"We found that the odds of having elevated depressive symptoms among individuals with the highest serum folate levels were about half that of those with the lowest levels," lead investigator May A. Beydoun, PhD, MPH, National Institute on Aging, told Medscape Medical News.

The study was published online September 14 in Psychosomatic Medicine.

First Nationally Representative Study

Previous research indicates that high levels of total homocysteine (tHcy) and low levels of folate and vitamin B12 are associated with depression or elevated depressive symptoms in adults.

However, investigators note that earlier studies examining the impact of low folate, low vitamin B12, and elevated tHcy status simultaneously on depressive symptoms did not examine interaction among those 3 risk factors and have had inconsistent findings as to the individual associations.

"To our knowledge this is the first nationally representative study conducted among U.S. adults after mandatory fortification of food with folic acid that examines associations of serum folate, vitamin B12, and tHcy levels with depressive symptoms," they write.

For the study the researchers used cross-sectional data from NHANES from 2005 to 2006 by assessing interactions (2 way and 3 way) among the 3 exposures and testing effect modification of the associations by sex.

The study sample included 2524 adults aged 20 to 85 years with complete data on demographics, diet, plasma folate, vitamin B12, and tHcy status, as well as information on physical activity, smoking status, blood pressure, and depressive symptoms.

Depressive symptoms were measured using the Patient Health Questionnaire (PHQ), and elevated symptoms were defined as a PHQ total score of 10 or greater.

Study Underpowered to Detect Effect in Men

With an odds ratio of 0.52 (95% confidence interval [CI], 0.35 – 0.76), adjusted analyses revealed that among the total population the odds of having elevated depressive symptoms was close to half that in the lowest tertile.

Further, with an odds ratio of 0.37 (95% CI, 0.17 – 0.86), the likelihood of women in the highest tertile of serum folate (mean ± SE, 21.1 ±0.29 ng/mL) to experience elevated depressive symptoms was about a third that of their counterparts in the lowest tertile (7.02 ± 0.08 ng/mL).

The study showed no relationship between B12 and tHcy levels and elevated depressive symptom risk — a finding that is consistent with previous research the researchers note.

In addition, researchers report that B12 and tHcy did not interact with folate status to affect its inverse association with depressive symptoms among women.

However, elevated homocysteine level was positively associated with elevated depressive symptoms in adults 50 years and older.

Although a significant association between folate levels and risk for elevated depressive symptoms was only observed in women, the investigators believe this is because the study was underpowered to detect the effect in men.

Boosting Folate Levels

The investigators point out that although the study has several strengths, it also has limitations, including its cross-sectional design, which prevents examination of the relationship between depression and serum folate levels over time.

Therefore, they note, it is possible that reverse causality is at play such that depressed individuals may be more likely to have a poor diet and therefore lower folate intake than nondepressed individuals.

Future interventions to improve mental health outcomes among US adult should focus on increasing levels of serum folate say investigators.

For instance, said Dr. Beydoun, clinicians should consider screening patients with depressive symptoms for serum folate and, if indicated, consider supplementation in addition to standard antidepressant therapy.

In addition, dietary and lifestyle advice to enhance serum folate should also be considered. Such counseling, she said, should include education about folate-rich foods, the beneficial effect of physical activity on folate levels, and the negative impact of cigarette smoking.

Diet Important in Mental Health

Commenting on the study, Felice Jacka, PhD, a researcher from the University of Melbourne in Australia, who has conducted a number of studies examining the impact of diet on mental health status, said given the fact that previous studies have reported this relationship the results are not surprising.

"However," she said, "the NHANES data are very good quality and, therefore, a very good vehicle to examine the relationships between nutritional status and mental health."

"This is the first large-scale population-based study in the US to show that folate status is associated with the presence of depressive symptoms since the fortification of foods with folate became mandatory," she added.

Dr. Jacka said this study also lends further support to the premise that diet is an important factor for mental health in the general population.

"It also suggests that blood tests to examine folate and homocysteine levels (and levels of other nutrients) in individuals with depressive symptoms may be of utility in clinical settings. If nutrient deficiencies and/or excess homocysteine are identified, dietary and/or supplementation strategies could then be considered," she said.

The study authors have disclosed no relevant financial relationships.

Psychosom Med. Published online September 14, 2010.

Wednesday, September 22, 2010

Nonpharmacologic Interventions for Spinal Stenosis

From Medscape Nurses
Barbara Resnick, PhD, CRNP

Pathophysiology of Spinal Stenosis

Spinal stenosis is a narrowing of the spinal canal or neural foramina producing root ischemia and neurogenic claudication. There is compression of neural structures, which also compress the vascular supply of nerves so that symptoms are predominately those of neural ischemia. Both the neural canal and the neural foramen are narrowed when the spine is in extension, and they are opened when the spine is in flexion.
Therefore, the pain associated with the compression is most often temporary. Fortunately, the pain associated with the nerve compression induces patients to change position and relieve nerve pressure before permanent neurologic damage is done.

Daniel Lieberman, MD, from the Arizona Center for Neurosurgery, Phoenix, Arizona,[1] provided an extensive review of the pathophysiology of spinal stenosis and described this as a slow stroke of the spine.
Due to bone changes, there is bulging and herniation of the vertebral body and a narrowing of the spinal canal. Pain occurs because of narrowing of the spinal canal and a subsequent decrease in oxygenation of the nerve.
Increased physical activity further increases oxygen demand, causing an infarct to the nerve root and exacerbation of pain. A complete infarct or stroke occurs very slowly over time.

There may be either central or lateral recess stenosis. In cases in which there is lateral recess stenosis, the patient will experience compression of the nerve roots and may have severe radicular symptoms including numbness in the toes with exercise. With central stenosis, there is compression of the spinal cord or myelopathy, and the patient will be more likely to complain of falls and a sensation that his or her "legs go out" with physical activity or exercise.

Diagnosis of Spinal Stenosis

Diagnosis of spinal stenosis is best done in the office setting by obtaining a focused history, observing the patient with regard to functional activities, and attempting to replicate pain via positioning. The following are typical findings in patients with spinal stenosis:

1.Patients are usually 60 years old or older;
2.Symptoms of stenosis are usually unilateral or bilateral leg pain, with or without back pain;
3.Pain occurs when the patient is upright and particularly when walking;
4.Typical symptoms are leg pain, numbness, and weakness developing after patient walks a predictable distance;
5.Patient seeks relief by sitting, leaning forward to "relieve pressure," putting his foot on a raised rest, or lying down; and
6.Common denominator is changing the position of the spine from extension to flexion.
A Phalen's test is particularly useful in making the diagnosis of spinal stenosis. This test attempts to reproduce symptoms of leg pain, weakness, or numbness by causing neural ischemia. The patient is asked to stand in full extension for a minute. A positive test occurs if an increase in leg symptoms is noted, followed by a rapid relief of these symptoms by having the patient bend forward with hands on the examination table and one foot on a stool.

Magnetic resonance imaging (MRI) without contrast should be done to make the final diagnosis and facilitate treatment options. The MRI can also help to differentiate spinal stenosis from other possible causes of back pain such as evidence of a spinal tumor or compression fracture. It is likely with fracture, however, that the pain will be localized more to the back rather than presenting as radicular pain.

Treatment Options for Spinal Stenosis
Nonsurgical interventions should clearly be implemented prior to surgical intervention. These interventions generally require behavior change and lifestyle alterations, and, as such, may not be easily achieved. Numerous motivational interventions can be implemented to facilitate behavior change.[2] The Table provides an overview of techniques. As appropriate, patients should be encouraged to reduce weight to achieve a body mass index that is appropriate for their given age and gender. In addition to weight loss, exercise should be strongly encouraged. The ideal exercise for spinal stenosis is swimming, which exercises all back muscles, or water walking, which is nonweight bearing. Pain should be relieved so that exercise and physical activity can be enhanced. Patients should be informed repeatedly that remaining sedentary to control pain will only further exacerbate disease.

Table. Motivational Interventions for Behavior Change
Factors Specific Interventions to Improve Motivation to Perform Healthy Behaviors
Efficacy Beliefs Interventions to strengthen efficacy beliefs:

1.Verbal encouragement of capability to perform -- SPELL out clearly the activity to be performed
2.Expose older adult to role models (similar others who successfully perform the activity)
3.Decrease unpleasant sensations associated with the activity
4.Encourage actual performance/practice of the activity

Eliminate Unpleasant Sensations (pain, fear, hunger) 1.Facilitate appropriate use of pain medications to relieve discomfort
2.Use alternative measures such as heat/ice to relieve pain associated with the activity; or encourage low calorie snacks to relieve hunger
3.Cognitive therapy:
1.Explore thoughts and feelings related to sensations
2.Help patient develop a more realistic attitude to the pain (ie, pain will not cause further bone damage)
3.Use relaxation and distraction techniques
4.Use graded exposure to overcome fear of falling

Individualized Care 1.Demonstrate kindness and caring to the patient
2.Use humor
3.Provide positive reinforcement following a desired behavior
4.Recognize individual needs and differences
5.Make it fun, new, or different

Spirituality 1.Explore the influence of spirituality and traditional religion and, as appropriate, encourage the patient to participate in this
2.Physically being with the older adult, and listening
3.Use life review
4.Encourage spiritual experiences: pets, children, journal-keeping, reading, friends, prayer

Social Support 1.Evaluate the presence and adequacy of social network
2.Teach significant other(s) to verbally encourage/reinforce the desired behavior
3.Use social supports as a source of goal identification

Goal Identification 1.Develop appropriate realistic goals with the older adult
2.Set goals that can be met in a short time frame -- daily or weekly
3.Set goals that are challenging but attainable
4.Set goals that are clear and specific

Pain management should be instituted using pain guidelines developed for care of older adults.[3] Gabapentin, Dr. Lieberman indicated, may not be useful for pain control in spinal stenosis because the pain does not come from within the nerve root. Epidural steroid injections are an option for pain control if medications are not fully relieving symptoms.[4] Epidural injections should control pain for a week. Alternative treatment options such as acupuncture can likewise be tried, although there are no randomized controlled trials to demonstrate the effectiveness of this treatment.

Back braces for management of pain can be used, although it should be stressed to patients that braces should not be used indefinitely. Specifically, it was recommended that the back brace not be used for more than 8 weeks because it weakens muscles. Dr. Lieberman suggested that patients be told to wear the brace for a 4-week period and then begin tapering off the brace.

Surgical Interventions: When All Else Fails
Surgical intervention is sometimes appropriate, and surgery essentially opens the spinal column, relieves the pain, and improves nerve oxygenation. Surgical interventions, specifically laminectomy or the more conservative decompressive laminarthrectomy,[5] or techniques such as laminoplasty[6] have all been shown to be effective in relieving pain and improving symptoms. Certainly, however, the surgical risks should be weighed against potential benefits, and surgical interventions should not be implemented until all other interventions have been attempted.

Patients with back pain should be carefully evaluated to establish if there is evidence of spinal stenosis. Once a diagnosis of spinal stenosis is made, conservative interventions, including weight loss if indicated and adherence to regular exercise, should be initiated. Certainly pain management should also include use of appropriate analgesic agents, epidural injections, and alternative treatments such as acupuncture. Likewise, back braces and supports can be used for short periods of time if they help with pain relief. If symptoms persist following implementation of conservative treatments, surgical intervention should be considered as this can effectively relieve nerve compression and thereby decrease pain and allow the patient to return to optimal function and quality of life.

Friday, September 17, 2010

Weight Control and Exercise Could Prevent 20% of Colon Cancer

From Medscape Medical News
Zosia Chustecka

September 16, 2010 — Around 20% of colon cancer in European countries could be prevented if the whole population managed to reach optimum levels of weight and physical activity, suggest new projections.

The data are reported in the September issue of the European Journal of Cancer, which is dedicated to cancer prevention.

An increasing proportion of the European population now has a body mass index (BMI) higher than 25 kg/m2, and few Europeans are engaging in the amounts of physical activity recommended by current guidelines (at least 30 minutes of moderate-intensity activity 5 or more days a week), the researcher note.

The researchers set out to predict what would happen if the European population managed to maintain a mean BMI of 21 kg/m2 and if all countries had a level of physical activity similar to that seen in the Netherlands, where both cycling and walking are popular.

They used the PREVENT statistical modeling method, which was developed at Erasmus University in the Netherlands and is frequently used in the European Union's EUROCADET project.

"We know that large numbers of colon cancer cases could be avoided by reducing exposure to risk factors," said senior author Andrew Renehan, PhD, FRCS, FDS, from the School of Medicine, University of Manchester, United Kingdom. And 2 of the most easily controllable risk factors are physical inactivity and excess weight, he added.

"The predictive modeling is beginning to tease out the independent relevance of each of these factors in the prevention of colon cancer," he said in a statement.

"Preventing weight gain and encouraging weight reduction seem to be most beneficial in men, but for women a strategy with a greater emphasis on increasing physical activity would be more effective," he explained.

Colon Cancer Increasing

Colon cancer rates are increasing in Europe; they have been on the rise since 1975. It is the second most common cancer in Europe and the second most common cause of cancer death, the researchers note.

In a previous study, Dr. Renehan and colleagues attributed the increasing rates of all cancers to increasing obesity in European countries. They estimated that in 2008, new cancers attributed to excess body weight affected 3.2% of women and 8.6% of men; this was an increase from the estimates for 2002, which projected that excess weight was related to new cancers in 2.5% of men and 4.1% of women.

Those data were presented at the 2009 meeting of the European Cancer Organization, and reported by Medscape Medical News at the time.

"People in Europe are gaining weight," Dr. Renehan said at the time, "and it is projected to keep rising."

In the new study, the researchers used the computer model to look at what would happen if Europeans continued to grow fatter, using a hypothetical scenario in which obesity levels increased at the same rate as they have in the United States. They predicted that this would lead to an increase in the number of new colon cancer cases of between 0.7% and 3.8%, depending on the European country.

Then they hypothesized a scenario in which Europeans managed to control their weight and managed to achieve an optimum BMI of 21 kg/m2. They calculated that by the year 2040, this weight-control strategy would prevent between 2% and 18% of colon cancer cases across the countries they studied. The benefits were much higher for males (13.5% to 18%) than for females (2.3% to 4.6%), and most benefit would be seen in British males (in whom 18% of new colon cancer cases could be prevented).

This "underlines the importance of stopping and reversing the ongoing increase in overweight and obesity prevalence," the authors note.

When the team considered physical activity, they found that the Netherlands had the highest rates, which they attributed to a high frequency of bike use, often as a means of transportation. They also found high levels of walking.

Using the Netherlands as the ideal, the researchers predicted what would happen if other countries adopted the same amount of physical activity. They found that overall, 17.5% of new colon cancer cases could be prevented by 2040, with the most benefit in Spanish females (in whom 21% of new colon cancer cases could be prevented).

"We can safely say that increasing physical activity across Europe to the level already achieved in the Netherlands, where everyone cycles, would be of substantial benefit," said coauthor Jan-Willem Coebergh, MD, PhD, from Erasmus University.

"In summary, the changes in physical activity and/or mean levels of overweight in the selected European populations would result in quite substantial effects on future colon cancer rates," the authors conclude.

The researchers have disclosed no relevant financial relationships.

Eur J Cancer. 2010;46:2605-2616.

Zosia Chustecka has disclosed no relevant financial relationships.

Sunday, September 12, 2010

Mild Cognitive Impairment Affects 16% of Nondemented Elderly, More Prevalent Among Men

From Medscape Medical News

Susan Jeffrey

September 10, 2010 — A new report finds a prevalence of mild cognitive impairment (MCI) of about 16% among elderly people free of dementia, with a higher prevalence among men than women.

The main purpose of this study was to determine the prevalence of MCI among a random sample of residents of Olmstead County, Minnesota, Ron C. Petersen, MD, PhD, from the Department of Neurology at Mayo Clinic in Rochester, Minnesota, told Medscape Medical News.

"As we suspected, there's a fair amount out there, and if you add the proportion of people with MCI to the proportion of people who already have dementia or Alzheimer's disease, you're at 25% to 30% of the population," Dr. Petersen said. "That's a huge number and it going to become increasingly large as time goes on."

Their research, part of the Mayo Clinic Study of Aging, appears in the September 7 issue of Neurology.

Earlier in the Process

The field of aging and dementia has been moving toward trying to identify patients as early as possible in the disease process in hopes of one day modifying the course of disease.
"MCI is considered an intermediate state between the cognitive changes of aging and the earliest clinical features of dementia, particularly Alzheimer's disease (AD)," they write.

There have been other epidemiologic studies of MCI, "but most investigators retrofitted the criteria for MCI to previously collected clinical information, used a variety of detection procedures, and implemented the MCI diagnostic criteria using different algorithms," Dr. Petersen and colleagues point out. "By contrast, we evaluated in person a population-based sample specifically to detect MCI and its subtypes using published diagnostic criteria."

In this analysis, they evaluated an age- and sex-stratified random sample of residents of Olmstead County who were between the ages of 70 and 89 years on October 1, 2004, using the Clinical Dementia Rating Scale, as well as neurologic and neuropsychological testing to assess 4 cognitive domains, including memory, executive function, language, and visuospatial skills.

The data generated on each individual was then reviewed by an adjudication panel and assessed as MCI, AD, or normal cognition.

Of 1969 participants assessed, 329 had MCI, for a prevalence of 16%; most cases were amnestic MCI.

Table. Prevalence of MCI in Nondemented Elderly 70 to 89 Years Old in Olmstead County

Group Prevalence, % (95% CI)
Any MCI 16.0 (14.4 – 17.5)
Amnestic MCI 11.1 (9.8 – 12.3)
Nonamnestic MCI 4.9 (4.0 – 5.8)

CI = confidence interval; MCI = mild cognitive impairment

The prevalence of MCI increased with age and, as has been previously reported by this group, was more common in men; the prevalence odds ratio for men vs women was 1.54 (95% confidence interval, 1.21 –1.96), after adjustment for age, education, and nonparticipation.

"The higher prevalence of MCI in men may suggest that women transition from normal cognition directly to dementia at a later age but more abruptly," the study authors speculate.

"Because evidence indicates that Alzheimer's disease may cause changes in the brain 1 or 2 decades before the first symptoms appear, there is intense interest in investigating MCI and the earliest stages of cognitive decline," said National Institute on Aging (NIA) Director Richard J. Hodes, MD, in a statement from the NIA that provided much of the funding. "While more research is needed, these findings indicate that we may want to investigate differences in the way men and women develop MCI, similar to the way stroke and cardiovascular disease risk factors and outcomes vary between the sexes."

The prevalence of MCI was also higher in those who reported they had never married and those with the known AD risk alleles APOE ε3ε4 or ε4ε4. The prevalence of MCI was significantly lower with increasing years of education (P for linear trend < .0001).

New Definition

At the recent Alzheimer's Association International Conference on Alzheimer's Disease (ICAD) 2010 in Honolulu, Hawaii, in July, draft reports from 3 workgroups were presented that will form the basis for new diagnostic criteria for MCI and AD — the first update of the current criteria in 25 years — as well as outlining a new category of preclinical AD.

The workgroups were convened by the NIA and the Alzheimer's Association to update criteria established by the National Institute of Neurological Disorders and Stroke/Alzheimer's Disease and Related Disorders Association — now the Alzheimer's Association — in 1984.

Dr. Petersen participated on the MCI committee, not surprising because his work largely established the concept.

"The committees are entertaining should we be looking earlier in the clinical spectrum of impairment to move the threshold for what we call Alzheimer's disease," he said. "Right now it's at the dementia stage where people are impaired in multiple cognitive areas, and they are functionally impaired."

There is a move to back a diagnosis of AD into the MCI stage, he noted, "because the sooner we pick it up, the more likely we'll be able to do something about it. But the challenge with moving it back to the MCI stage is that not everybody who's memory impaired will necessarily develop Alzheimer's disease and that's where the role of imaging and biomarkers come in that were discussed at ICAD and are the subject of further discussion and further research

"The purpose is hopefully the sooner we identify these people who are in the early stages we'll be able to do something about it in the future," he said.

The study was supported by the National Institutes of Health and the Robert H. and Clarice Smith and Abigail van Buren Alzheimer's Disease Research Program. The study was made possible by the Rochester Epidemiology Project. Dr. Petersen serves on scientific advisory boards for Elan Corporation, Wyeth, and GE Healthcare; receives royalties from the publication of Mild Cognitive Impairment (Oxford University Press), and receives research support from the National Institutes of Health/NIA. Disclosures for coauthors appear in the paper.

Neurology. 2010;75:889-897.

Thursday, September 9, 2010

Midlife Stressors May Increase Risk of Dementia in Women

From AccessMedicine from McGraw-Hill
S. Andrew Josephson, MD

08/27/2010; AccessMedicine from McGraw-Hill © 2010 The McGraw-Hill Companies

Dementia is an important health concern that has become even more prevalent with an aging population. Identification of modifiable risk factors for dementia is a key goal of research given the potential to prevent this potentially devastating and costly disorder. Some lines of evidence point to stress and its relation to cognitive decline as one such risk factor, perhaps through activation of glucocorticoid pathways. A recent study (Johansson et al, 2010) used a unique data set in order to explore whether stress indeed is a risk factor for the development of dementia.

The authors performed a prospective longitudinal study using a cohort of women enrolled in the Prospective Population Study of Women in Gothenburg, which began in 1968 by enrolling 1462 patients born from 1908 to 1930. All nondemented subjects were asked about stress as part of a standard evaluation in 1968, 1974, and 1980.
Participants were asked if they had experienced any period of stress greater than 1 month in relation to work, health, or family situation.
Stress was defined for the subjects as feelings of irritability, tension, nervousness, fear, anxiety, or sleep disturbance. Responses included no stress, one period of stress during the last 1 year or 5 years, multiple periods of stress during the last 5 years, or constant stress during the last 1 or 5 years.
Dementia was diagnosed in these patients using standard criteria and serial neuropsychological examinations including informant interviews. Multiple possible confounders were recorded, including education, marital status, vascular risk factors, and weight.

Frequent/constant stress within 5 years was reported in 20% of the patients in 1968, 23% in 1974, and 15% in 1980. Of the 1415 patients assessed in 1968, 161 (11%) developed dementia over a 35-year follow-up period. A total of 105 dementia cases were thought to result from Alzheimer's disease (73 of whom had coexisting cerebrovascular disease), 40 from pure vascular dementia, and 16 from other causes of dementia. The risk of dementia was increased in patients reporting frequent/constant stress in 1968 [hazard ratio (HR), 1.60; 95% confidence interval (CI), 1.10–2.34], in 1974 (HR, 1.65; 95% CI, 1.12–2.41), and in 1980 (HR, 1.60; 95% CI, 1.01–2.52). Adjustments for multiple confounders did not change the results. Occasional stress was not associated with risk of development of dementia.

Patients with frequent/constant stress were found to have an increased risk of developing Alzheimer's disease, with and without coexisting cerebrovascular disease, but not an increased risk of pure vascular dementia. Associations held true even when examining dementia onset before and after age 70 separately as well as with exclusion of those with onset of dementia before 1992 in an attempt to exclude those whose stress may have been an early manifestation of incipient dementia.

This intriguing study certainly has a number of limitations.
Patients' ability to cope with stress or view a situation as stressful may be variable; this variability may or may not be related to underlying neuropathology.
A single question probably does not robustly assess life stress; however, recall bias is certainly diminished using this methodology of direct questioning at different time points rather than relying on recall of stress many, many years prior.
For the clinician, this study suggests that midlife stress may indeed serve as a risk factor for the development of dementia later in life. Whether mitigation of this stress will help prevent some forms of dementia or delay their onset remains to be seen in future studies.


Wednesday, September 8, 2010

Effect of Exercise on Oxidative Stress: A 12-month Randomized, Controlled Trial

From Medicine and Science in Sports and Exercise®

Peter T. Campbell; Myron D. Gross; John D. Potter; Kathryn H. Schmitz; Catherine Duggan; Anne Mctiernan; Cornelia M. Ulrich

Posted: 08/23/2010; Medicine and Science in Sports and Exercise®. 2010;42(8):1448-1453. © 2010 American College of Sports Medicine


Purpose: This study examined the effect of a yearlong exercise intervention on F2-isoprostane, a specific marker of lipid peroxidation and a general marker of oxidative stress.

Methods: In a randomized, controlled trial, 173 overweight or obese, postmenopausal, sedentary women were randomized either to an aerobic exercise intervention (60%–75% observed maximal HR) for ≥45 min·d−1, 5 d·wk−1 (n = 87), or to a stretching control group (n = 86), on an intent-to-treat basis. Baseline and 12-month measures included urinary F2-isoprostane, maximal O2 uptake, body weight, body fat percentage, waist circumference, and intra-abdominal fat surface area. Urine samples were available from 172 and 168 women at baseline and 12 months, respectively.
Results: During the 12-month study, controls minimally changed maximal O2 uptake (+0.2%) and body weight (+0.1 kg), whereas exercisers increased maximal O2 uptake (+13.6%; P < 0.0001 vs controls) and decreased body weight (−1.3 kg; P = 0.007 vs controls). F2-isoprostane increased slightly among controls (+3.3%) and decreased in exercisers (−6.2%), although the effect was not statistically significant (P = 0.26). In planned subgroup analyses, F2-isoprostane decreased linearly with gain in maximal O2 uptake (P trend = 0.005) relative to controls; exercisers who increased maximal O2 uptake by >15% decreased F2-isoprostane by 14.1% (P = 0.005 vs controls). A borderline statistically significant trend was observed between decreased waist circumference and F2-isoprostane (P = 0.06). Similar subgroup analyses by 12-month changes in body fat percentage, weight, and intra-abdominal fat were not statistically significant.

Conclusions: These findings suggest that aerobic exercise, when accompanied by relatively marked gains in aerobic fitness, decreases oxidative stress among previously sedentary older women and that these effects occur with minimal change in mass or body composition.


Oxidative stress occurs when the production of reactive species, derived largely from oxygen and nitrogen, exceeds degradation by the antioxidant defense system.
The ensuing damage to DNA, protein, and lipid has been implicated in cardiovascular and pulmonary diseases, diabetes, neurodegenerative disorders, and some cancers.
Thus, intervention strategies to reduce oxidative stress, especially among overweight/obese persons who generally have high oxidative stress levels,have widespread appeal. Such efforts with human study subjects have been hindered by difficulties in the measurement of oxidative damage. Recently, however, sensitive and stable methods have become available to measure F2-isoprostanes
F2-isoprostanes are a family of isomeric F2-prostaglandin-like compounds, derived from free radical-catalyzed peroxidation of arachidonic acid, independent of the cyclooxygenase enzyme. A recent multi-institutional study concluded that F2-isoprostane was the most accurate method to assess oxidative stress in vivo from urine or plasma samples.[9]

Reduced oxidative stress, probably achieved through improved antioxidant defenses and/or reduced reactive species formation, may be one mechanism that links physical activity to reduced risk of chronic disease.[3,19] Noncontrolled exercise intervention studies among premenopausal women have noted 25%[6] and 34%[18] decreased F2-isoprostane concentrations after 12–15 wk of exercise training; however, no intervention effects were observed in an 8-wk controlled exercise trial among older patients with type 2 diabetes.[15] Given the lack of data on this topic, we investigated the effect of a yearlong aerobic exercise intervention compared with a stretching control program on F2-isoprostane concentrations in postmenopausal women. We hypothesized that the 12-month exercise intervention would decrease F2-isoprostane and that this effect would be mediated by changes in maximal O2 uptake and by measures of body size/fat distribution.

This work was conducted with ancillary funding, using previously collected urine specimens and data from the Physical Activity for Total Health study ( Identifier: NCT00668174). The main objective of the parent trial was to examine the effects of exercise on steroid hormones among 173 postmenopausal, previously sedentary, overweight/obese women, as described previously.[11–13] A subgroup of participants (n = 115) from the parent trial, who met additional inclusion criteria, were included in separately funded studies of the effects of exercise on immune function[5] and inflammation.[4]

We examined the effect of a yearlong aerobic exercise intervention compared with a stretching control program on urinary F2-isoprostane, a marker of systemic oxidative stress, among previously sedentary, overweight/obese, postmenopausal women. Overall, exercisers decreased F2-isoprostane concentrations, as predicted by our primary hypothesis, but the effect was not statistically significant, except in planned analyses by strata of gain in aerobic fitness.

Few previous studies have examined the effects of exercise alone on F2-isoprostane concentrations,[6,15,18] and no earlier studies, to our knowledge, were conducted exclusively among postmenopausal women. These studies suggest that exercise may reduce quite strongly F2-isoprostanes among relatively younger women,[6,18] whereas this beneficial effect may be attenuated among older study subjects, as observed currently and previously.[15] The three earlier studies and the current study noted similarly decreased body mass and increased aerobic fitness after exercise intervention, despite the wide range of intervention periods and age groups studied. Thus, these data suggest a potential age effect for the capacity of exercise to reduce oxidative stress. The mechanisms to explain such an effect are discussed in detail elsewhere[2] and are largely on the basis of experiments with laboratory animals: essentially, older animals have been observed to experience damage to cardiac and skeletal muscle after short-term exercise training if it is not initiated before a certain age, indicative of a physiologic age threshold. Alternatively, if exercise is initiated before this age, older animals experience the same health benefits as younger exercising animals. However, it is important to note that the older adults in the current study, and the participants in the previous study,[15] marginally decreased oxidative stress levels, although the effects were not statistically significant, suggesting that the laboratory animal data are not entirely generalizable to humans.

We observed an inverse linear association between aerobic fitness and oxidative stress, suggesting a hormetic effect of exercise training.[10] This finding for aerobic fitness and oxidative stress complements recent results from a subset of participants in this trial (n = 115) where we reported that the effect of exercise on inflammation (C-reactive protein and serum amyloid A) was restricted to participants who were obese (BMI ≥ 30 kg·m−2 or waist circumference > 88 cm) at baseline.[4] In contrast, baseline obesity status did not modify the influence of exercise on F2-isoprostane in the current study (data not shown). For our study participants, in particular, these results suggest that gains in aerobic fitness improve oxidative stress levels, probably because of exercise-induced adaptations of the antioxidant defense system,[3,8,16] and this effect occurs independent of general or abdominal obesity status. Although our subgroup analyses among exercisers by strata of weight/fat loss were largely not statistically significant, it is worth noting that this trial was not designed to elicit much weight loss, and our exercise participants only reduced body weight by approximately 1.3 kg, on average. Therefore, we could not assess the effects of much weight/fat loss on oxidative stress, a limitation that future studies should address.

Particular strengths of this study include the following: the selection of a sensitive and stable biomarker for oxidative stress;[9] the long period of exercise intervention, with high participant retention; the good participant adherence to the exercise protocol; the bona fide effects of the aerobic exercise intervention, quantified by direct measures of maximal O2 uptake; and the gold standard randomized, controlled trial design. Limitations of this study include the highly homogeneous study sample that limits comparisons to other groups and the fact that we studied only one biomarker of oxidative stress, F2-isoprostane; future studies should consider other measures of lipid peroxidation, such as TBARS, and biomarkers that additionally reflect oxidative damage to protein and DNA.

In conclusion, in a randomized, controlled trial with excellent retention and good adherence to the aerobic exercise intervention, conducted among 173 previously sedentary, overweight/obese, postmenopausal women, we observed a modest reduction in F2-isoprostane overall that was not statistically significant. When exercisers were stratified by gain in aerobic fitness, as measured by maximal O2 uptake, an inverse and linear association was observed between aerobic fitness and F2-isoprostane, suggesting a training effect on oxidative stress.

Tuesday, September 7, 2010

Are you Ever too Old to have a Baby? The Ethical Challenges of Older Women Using Infertility Services

From Seminars in Reproductive Medicine
Art L. Caplan, Ph.D.; Pasquale Patrizio, M.D., M.B.E.

08/20/2010; Semin Reprod Med. 2010;28(4):281-286. © 2010 Thieme Medical Publishers


Older parenthood raises a variety of important factual and ethical questions. None of the questions have received sufficient attention despite the rapid expansion in the United States and other nations in the numbers of older parents.
We do not know much about the safety, economic, and psychosocial impact of these emerging practices on children or parents. Nor have there been many analytical considerations of the ethical issues raised. We argue in this article that there are reasons for concern when older persons seek to utilize fertility treatments, including the safety of pregnancy for older women, risks posed to children delivered by older mothers, issues around what constitutes safe conditions for having a child relative to the age of parents, and the importance of guaranteeing that someone will serve in the parental role should an older parent or parents become disabled or die.

To protect the best interest of children created by technology in new familial circumstances, internationally recognized and enforced standards for fertility clinics to follow ought to be enacted in making decisions about treating older parents seeking infertility services.

Programs offering fertility services in the United States and other nations are increasingly faced with requests from women of advanced reproductive age seeking assistance in becoming pregnant. Oocyte donation, new drugs, the technique of single intracytoplasmic sperm injection, and in vitro fertilization (IVF) afford older women the opportunity to give birth well beyond the natural limit imposed by menopause, and more and more women are taking advantage of this opportunity.[1–4] With egg freezing transitioning rapidly into a therapeutic option, it can be anticipated that more and more younger women will freeze their eggs for future use either in old age or even after their deaths.[5]

Older parenthood does and should raise a variety of important factual and ethical questions. None of the questions have received sufficient attention despite the expansion in the numbers of older parents. We do not know much about the safety, economic, and psychosocial impact of these emerging practices on children or parents. Nor have there been many analytical considerations of the ethical issues raised. Although it is imperative that more be done to monitor and evaluate older parenting, which uses infertility technology including postmortem birth, this article will focus on the key ethical questions raised.

One core ethical question is how to describe older parenting (and postmortem) fertility treatment. Are these instances of human experimentation and should doctors providing these services be held to the standard ethical requirements governing clinical research? If new technologies are being tried in novel ways where the risks and benefits are not well known, there may be a case for insisting that infertility interventions for patients who are very old only be done by doctors who have constructed research protocols and had them approved by appropriate peer review bodies.

Other questions abound. Should infertility programs discourage, tolerate, or encourage pregnancy in old age? Or, instead, should ethical programs try to discourage and constrain who it is that can bear a child in their later years? Should restrictions be in place on advertising and marketing in magazines, the Web, and other forums for fertility services that target older persons? And should governments, private insurance companies, and other third-party payers pay for fertility treatments for older patients

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Friday, September 3, 2010

No CV Benefit on Reducing Homocysteine

From Heartwire
Sue Hughes

June 22, 2010 (Oxford, United Kingdom)- Substantial long-term reductions in blood homocysteine levels with folic-acid and vitamin-B12 supplementation did not have beneficial effects on vascular outcomes in the large-scale SEARCHtrial.
But a silver lining of good news from the trial is that the vitamin supplements were not associated with any increase in cancer risk, which had been suggested in a previous study.

The trial, published in the June 23, 2010 issue of the Journal of the American Medical Association, was conducted by a team led by Dr Jane M Armitage (University of Oxford, UK).

Results from SEARCH were first reported by heartwire at the 2008 AHA meeting.

End of an Era

Armitage told heartwire that this large randomized trial "rounds off an era of trials with folic acid, which together suggest no benefit in reducing cardiovascular events."

While there is no doubt about the association between increased homocysteine levels and increased heart disease risk, our results suggest that this is not a causal association.
"This is another example of findings from observational studies leading us up the wrong path. While there is no doubt about the association between increased homocysteine levels and increased heart-disease risk, our results suggest that this is not a causal association.

Lowering homocysteine does not reduce that risk. There is probably a third party involved that increases risk of heart disease and increases homocysteine at the same time. So lowering homocysteine should no longer be the focus of our attention," Armitage commented.

She added: "That is not to say that foods high in folic acid will not be beneficial. Folic acid is found in fruit and vegetables, and these of course are good for you, but not necessarily because they contain folic acid."

On the cancer findings, Armitage said: "Our cancer results are reassuring. Most other trials have also shown no significant risk of cancer with folic-acid supplementation, but there was one trial that suggested a small increase in risk, which has probably received overselective emphasis. But it is important to be sure, as folate is added to food in some countries and is given to pregnant women to prevent neural-tube defects.
While we can never say never, our data do provide reassurance on the risk of cancer. But it would still be good to see longer-term data when considering cancer risk. We had seven-year follow-up in this study, but we are going to continue to follow our patients well into the future to provide even longer-term data."

In the paper, the researchers explain that observational studies have consistently indicated that patients with vascular disease have higher blood levels of homocysteine than do controls, and these differences precede the onset of disease and are independent of other risk factors. Daily supplementation with folic acid typically lowers homocysteine levels by about 25%, and the addition of vitamin B12 lowers it by a further 7%, and as these vitamins are inexpensive, there is considerable interest in using them to reduce the incidence of vascular disease.

They add that no definite protective effects of these vitamins have been seen in seven previous large-scale randomized trials, but it has been unclear whether this was due to insufficient numbers of events, too short a duration of treatment, attenuation of any effects by populationwide folic-acid fortification, or lack of real benefit. However, a subgroup analysis of the HOPE-2 trial and a meta-analysis of other trials have suggested a protective effect on stroke. To look at this issue further, they conducted the SEARCH trial, in which 12 064 UK survivors of MI were randomized to 2-mg folic acid plus 1-mg vitamin B12 daily or matching placebo.

28% Reduction in Homocysteine

Results showed that allocation to the study vitamins reduced homocysteine by a mean of 3.8 µmol/L (28%). During 6.7 years of follow-up, there was no difference in the primary end point of first major vascular event (coronary death, myocardial infarction [MI], any revascularization, or stroke) between the two groups. There was also no difference in other major secondary end points or in the incidence of cancer between the two groups.

The authors note that a meta-analysis of individual patient data from eight homocysteine lowering trials (including SEARCH), which has been submitted for publication and includes data on 37 485 individuals, confirms that folic-acid supplementation has no significant effects on major vascular events (RR 1.01) or any of its separate components.

Armitage commented to heartwire : "This meta-analysis gives an even more definitive answer that there is no benefit on heart disease of folic acid and should be the end of this issue," she said.

On the cancer findings, the researchers explain that there have been concerns that folic acid may play a role in carcinogenesis and suggestions that the introduction of folic-acid fortification in the US was linked to an increase in colorectal-cancer incidence during the late 1990s. While previous trials have shown mixed results in this issue, they state: "By contrast, with more than 1300 incident cancers during up to seven years of treatment with 2-mg folic acid and 1-mg vitamin B12 daily, SEARCH provides no evidence of adverse effects on cancer at any particular site."

Wednesday, September 1, 2010

Fluids and electrolytes during Exercise

Dehydration impairs performance; therefore, athletes must remain well hydrated.

Adequate fluid intake is approximately 2.2 L/d for women aged 19-30 years, and increased drinking is required for active individuals or those in hot environments

Athletes should consume 400-600 mL of fluid 2 hours before exercising.
During exercise, 150-350 mL (6-12 fluid ounces [fl oz]) should be ingested every 15-20 minutes.
For exercise lasting longer than 1 hour or occurring in hot environments, the fluid should be a drink containing carbohydrates and electrolytes.

Postexercise meals should include fluids and foods containing sodium, because diuresis occurs with the ingestion of plain water.

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