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Anti-Depressants increase bone fractures in older women.

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Do anti-depressants increase bone fractures?  Evidence from a new study says yes.  Anti-depressants in the SSRI family have been shown to increase risk of bone fracture before. The new study, hot in Google News, looked at women who were new users without a diagnosis of depression (and presumably prescribed SSRIs for menopausal symptoms) and their risk of bone fracture.  SSRIs are sometimes used to treat menopausal symptoms such as night sweats, hot flashes and mood changes.  Their use has increased since estrogen replacement therapy fell into disfavor.    This study is different and important because:

 

  • Women who are using SSRIs to treat menopausal symptoms are often prescribed doses lower than those used to treat women suffering from depression.
  • We didn’t know if low-dose SSRIs would increase fracture risk
  • Data was available for very large numbers of women (more than 100,000 for each group).  This makes for some pretty reliable conclusions.

Study Structure

Subjects were between the ages of 40 and 64 who had not been diagnosed with depression or other mental disorder.  They were compared with a similar group of women who were taking proton pump inhibitors or H2 antagonists.  These are drugs often used to treat GERD (Gastroesophgeal reflux disease).  They may also increase risk of bone fracture because of their ability to interfere with calcium absorption . . . but the risk appears to be very small.

Study results

After six months of SSRI use, fracture risk was greater than it was among women who did not use SSSRIs.   The difference between the two groups decreased slightly over time, but was still significant after 5 years.  So yes, it looks like anti-depressants increase bone fractures.  At least SSRI anti-depressants.

Conclusions and further thoughts

This may be the first study to show an increased risk of fracture among peri-menopausal women using SSRIs to treat menopausal symptoms.   The study’s authors suggest that use of SSRIs to treat menopause be limited to shorter durations.  Researchers were not able to look at the effects of different doses.  (The actual doses used were not available). Or differences according to type of SSRIs.

Other things to consider

Bone density and fracture risk are dependent on many factors that were not available to the researchers.  Nothing was known about the women’s exercise habits or diet.  Bone building exercise might offset any bone weakness potentially caused by SSRIs.  A good diet and vitamin D might as well.  More research would be needed to understand risks from SSRIs and how they might be controlled.

The two groups were chosen for study not because they were ideal for them, but because the data were available.  It would be nice to have a study that looked at SSRIs, untreated depression, untreated menopause, bone density, fracture risk, and diet.  But studies are expensive.  We are currently in a period where the proportion of funds we devote to research has fallen severely.  According to Reuter’s journalist Sharon Begley:  Government spending on science is the lowest it’s been since WWII, and it’s holding back potentially life-saving advances.  You can write your congressman and tell him or her that research is important.    We all benefit from research.

Andrea B. Kirk, PhD

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Ito T, & Jensen RT (2010). Association of long-term proton pump inhibitor therapy with bone fractures and effects on absorption of calcium, vitamin B12, iron, and magnesium. Current gastroenterology reports, 12 (6), 448-57 PMID: 20882439

Sheu YH, Lanteigne A, Stürmer T, Pate V, Azrael D, & Miller M (2015). SSRI use and risk of fractures among perimenopausal women without mental disorders. Injury prevention : journal of the International Society for Child and Adolescent Injury Prevention PMID: 26113668

An anti-depression diet might be high in anti-oxidants and fermentable fiber, and low in saturated fats

Is there such a thing as an anti-depression diet?

Summary:

People who suffer from depression seem to experience more oxidative stress and inflammation than others.  A diet high in anti-oxidants, fermentable fiber and low in saturated and transfats may protect against inflammatory stress in the brain and elsewhere.  More research needed.  The topic is under investigation.

Introduction:

We recently posted an article about the role of oxidative and nitrosative stress and depression.  Oxidative and nitrosative stress can cause inflammation and damage to cells.  Depression is associated with brain shrinkage, impaired memory, loss of cognitive abilities and increased risk of Alzheimer’s disease.  There are probably more too.  People who are depressed tend to have poorer defense against oxidative damage.  Anti-oxidant and selenium levels also tend to be lower.  Are the anti-oxidants used up by heavy demand?  Or are people who are depressed less likely to eat well?  The answer could be both.

Depression and anti-oxidants

People who are depressed tend to have lower zinc, coenzyme Q10, vitamin E and glutathione than people who are not depressed.  These nutrients and biomolecules protect cells against lipid peroxidation, DNA damage, mitochondrial damage, and damage to proteins that occur with oxidative or nitrosative stress.  Nitrosative stress can result in addition of unwanted nitrogens to proteins.  This can change their structure and may trigger the immune system to attack them.  This type of damage may be related to the development of auto-immune disorders.

Can increasing anti-oxidants  and reducing inflammation decrease depression?

Researchers aren’t sure of the answer yet, but the possibility is under investigation.  If this turns out to be the case a change in diet and an aspirin might be helpful in treating depression.  Indeed, some researchers are trying to develop a depression diet that they hope will help alleviate depression or protect those at risk.

What might an anti-depression diet look like?

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An anti-depression diet would probably be high in anti-oxidants.  This would mean lots of fresh fruit and vegetables.  It might also mean more dietary fiber.  Dietary fiber as a cancer protectant has not proven to be as powerful as hoped.  However, some forms of dietary fiber contribute to anti-oxidant status when they are metabolized by gut microbiota.  An anti-depression diet should also probably be low in transfat (same for everyone btw) and low in saturated fatty acids.  Studies of mice fed diets high in saturated fatty acids have shown higher levels of brain inflammation than mice fed standard diets.  Scary add-on here: Mother mice fed a diet high in saturated fatty acids also produced off-spring that had higher levels of inflammation, even when they were fed a standard mouse diet.  The thought that maternal diet could predispose offspring to depression or other cognitive disorders is frankly scary. It’s hard for people who are severely depressed to take care of themselves.  But improving diet might be worth a shot.     NOTE: this article is meant to stimulate discussion and provide information.  Contact your health care provider for medical advice.

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Moylan S, Berk M, Dean OM, Samuni Y, Williams LJ, O’Neil A, Hayley AC, Pasco JA, Anderson G, Jacka FN, & Maes M (2014). Oxidative & nitrosative stress in depression: Why so much stress? Neuroscience and biobehavioral reviews, 45C, 46-62 PMID: 24858007

 

Maes M, Kubera M, Leunis JC, & Berk M (2012). Increased IgA and IgM responses against gut commensals in chronic depression: further evidence for increased bacterial translocation or leaky gut. Journal of affective disorders, 141 (1), 55-62 PMID: 22410503

 

Maslowski KM, Vieira AT, Ng A, Kranich J, Sierro F, Yu D, Schilter HC, Rolph MS, Mackay F, Artis D, Xavier RJ, Teixeira MM, & Mackay CR (2009). Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43. Nature, 461 (7268), 1282-6 PMID: 19865172

 

Pistell PJ, Morrison CD, Gupta S, Knight AG, Keller JN, Ingram DK, & Bruce-Keller AJ (2010). Cognitive impairment following high fat diet consumption is associated with brain inflammation. Journal of neuroimmunology, 219 (1-2), 25-32 PMID: 20004026

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Depression Brain. Folate and Anti-Oxidants can help protect against damage

Depression brain.  Depression damages the brain and contributes to memory problems

Depression is a brain disorder that interferes with many aspects of function.  The evidence for genetic susceptibility to depression is strong, although it may take a traumatic event, or even a series of traumatic events, to trigger it. The brains of people with depression differ from those of people who are not depressed.  Brain imagery studies show differences in brain regions related to cognition, sleep patterns, feeding behavior and sleep.  Studies have also demonstrated smaller brain volume, greater susceptibility to Alzheimers disease, heart disease and memory problems.  Depression is a bio-chemical problem that is strongly associated with other serious medical conditions that can further reduce quality of life and lifespan.

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A WODMASTERS Mona Lisa Hoists Her Kettlebells Shirt is a Mood-Lifter for sure.

How is depression related to other diseases?

There is increasing evidence that depression may increase risk of other diseases by changing body chemistry.  These alterations may lead to decreased levels of anti-oxidants and increased oxidative stress.

Depression Brain and the Chemical Stress of Depression

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Depression has been associated with elevated cortisol levels.  The general thought, originating with Hans Selye’s research, is that elevated cortisol leads to suppression of immune function.  There is a lot of good evidence supporting this, but more recent research indicates that even though cortisol levels may be elevated in depression, the immune system is not turned down– or at least not in the brain.  Increased immune activity can cause oxidative damage to surrounding tissues. One of the ways the immune system protects the body from attack is by blasting offensive material with highly reactive chemicals such as hydrogen peroxide.  The hydrogen peroxide blasts releases free oxygen, which damages the cell membranes of targets, and destroys them.  The blast is called an “Oxidative Burst.”  Another type of “Blast” is created by production of nitric oxide.  That type of “blast ” is a nitrosative burst. These “bursts” can damage healthy cells, especially when there is no appropriate target, such as infectious organisms.  New research is showing that depression increases immuno-inflammatory activity.  This activity can damage:

  • Lipids and Cell Membranes.  This can cause cell death
  • Proteins.  Also not good.
  • DNA.  DNA damage can result in cancer
  • Mitochondria.  Mitrochondria are needed to produce energy for cells.

Depression is also associated with

  • Reduced neurogenesis (growth of brain cells)
  • Reduced brain volume (popularly known as “raisin brain.”)
  • Memory problems and etc.
  • Increased vulnerability to Alzheimer’s disease

Increasing immuno-inflammatory pathways can lead to decreases in production of melatonin and serotonin.

When the body increases activity of one pathway another pathway may be left with insufficient resources.  Upping the activity of the immune system may mean lowering activity of something else.  The molecule tryptophan is used in production of interleukins and tumor-necrosis factor alpha during activation of immunol-inflammatory pathways.  Tryptophan is also used in production of the neurotransmitter, Serotonin and the hormone melatonin.  Tyrptophan levels tend to be low in depressed people.  So are levels of serotonin and melatonin.  This may be because the demand for tryptophan is increased. Low serotonin is believed to be one of the factors causing the feelings of sadness and worthlessness of depression.  Anti-depressants such as Selective Serotonin Re-uptake Inhibitors (SSRIs) help maintain levels of serotonin.  Melatonin is a hormone that helps regulate the sleep cycle.   Sleep disorders are hallmarks of depression.  It gets a lot more complicated and there is a lot more biochemistry involved.  If you want to learn more check out the references at the bottom of this article.  The point I’m hoping to make is that people who suffer depression may also be suffering more oxidative stress than is good for them and that depression is more than a psychological problem.

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A question about depression.

Are the feelings of sadness, guilt, worthless , low serotonin and etc. secondary side effects of something else?  Robert Sapolsky has likened depression to the response one would have to a crushing physical injury.  Getting munched by a sabre-toothed tiger and surviving would mean an extended period of healing.  It would be good to get your immune system up and running, because bacterial infection would be sure to set in next.  Forget the neurotransmitters for now.  You should be asleep anyway.  Maybe in depression the body is settling in for a tedious recooperation and is then unable to turn off the response.  People can stay depressed for years. And apparently it can be very difficult to help break a patient out of it.  But what about long-term oxidative or nitrosative damage being done during the time someone is depressed?  Could increasing anti-oxidants help?  Could anti-oxidants protect depressed people from neuronal degeneration, shrunken brain volume, memory impairment and inability to think straight?

Anti-Oxidants and Depression.

Anti-oxidants may help.  Maybe.  There has been some interesting work on people who have genetic variants for an enzyme (MTHRF) important in folate metabolism.  Folate is a B vitamin.  Folate metabolites, like vitamins C and E, are powerful anti-oxidants.  Some people, for genetic reasons, are unable to metabolize folate very well.  People with genes that do not allow for efficient metabolism of Folate are at higher risk of depression (and several other disorders, including migraines).  By some counts, around 70% of people with major depressive disorder are poor folate metabolizers. People who have difficulty metabolizing folate can get around the problem by taking a folate supplement that is already in an advanced form: L-methylfolate.  In fact, some doctors are prescribing L-methylfolate along with anti-depressants to their depressed patients.  Deplin is a prescription L-methylfolate.  You can also get L-methylfolate non-prescription strength from health food stores or Amazon.  It is not yet understood how L-methylfolate may relieve depression.  But it is a strong anti-oxidant.  Does it help by reducing oxidative stress?  Would other anti-oxidants be helpful in treating depression, or in reducing the damage depression inflicts on the body?  We’ll be keeping on eye on research developments.

Final Takeaway

If you are suffering from depression get treatment and try to eat well.  Even if its hard.  A little L-methylfolate might help.

Papakostas, G., Shelton, R., Zajecka, J., Etemad, B., Rickels, K., Clain, A., Baer, L., Dalton, E., Sacco, G., Schoenfeld, D., Pencina, M., Meisner, A., Bottiglieri, T., Nelson, E., Mischoulon, D., Alpert, J., Barbee, J., Zisook, S., & Fava, M. (2012).L- Methylfolate as Adjunctive Therapy for SSRI-Resistant Major Depression: Results of Two Randomized, Double-Blind, Parallel-Sequential Trials American Journal of Psychiatry, 169 (12) DOI: 10.1176/appi.ajp.2012.11071114

Haroon E, Raison CL, & Miller AH (2012). Psychoneuroimmunology meets neuropsychopharmacology: translational implications of the impact of inflammation on behavior. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 37 (1), 137-62 PMID: 21918508

Shoulder blues depression and aging

Telomeres may shorten with depression but there are things you can do to protect them.

Telomere Depression and Aging

CrossFit WOD with social support to protect against depression and telomere shortening

Social support matters. Maybe this kid is protecting his father from depression and telomere shortening.

If you read the news you may have noticed articles on depression and telomere length.  There is no reason to think you are screwed and get more depressed. Or get depressed if you weren’t already. Improving your diet seems to increase telomere length.  So does exercise and stress management.

Telomeres protect DNA by capping the ends of chromosomes and preventing them from unraveling or tangling with one another. Telomeres shorten with each cell division. They shorten until they become too short to serve their protective function. At this point the cell will cease to divide and it becomes senescent. Telomere length is a marker of biological age. Shortened telomeres are also associated with inflammation and oxidative stress. Many diseases and maladies of advancing age are associated with short telomeres. Shortened telomeres have been noted in cancers, cardiovascular disease, dementia and Alzheimer’s disease.

Telomere depression: Does depression shorten telomeres?

Most recently, telomere shortening has been found in people suffering from depression. This may be one of the reasons why people who suffer from depression have poorer health and do not live as long as people who have not.  There is a lot of interesting research coming out on the biochemistry of depression. Click here for articles on folate deficiency and depression, mthfr variants and depression, and exercise and telomere length.

This is depressing.  Is there anything I can do to?

 

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So far research indicates that a healthy diet may protect telomeres. People who follow a Mediteranean Diet with lots of vegetables, olive oil, whole grains, legumes and fruit have longer telomeres than people who follow a diet high in saturated fat, refined grains, sugar, junk food, fried food etc. (Paleo diet followers: there is no research yet on how the paleo diet might protect telomeres. Best guess is that if you include lots of vegetables and use olive oil you will be better off than most.)

Exercise also seems to protect telomeres. Studies show that Masters Athletes have longer telomeres than their sedentary peers. This is good news for Masters Athletes.  A study of men with prostate cancer who underwent a lifestyle intervention program to increase fitness, diet, stress management and social support experienced an increase in telomere length five years later. The control group that did not receive lifestyle intervention showed decreased telomere length. Good news if you eat well and take care of yourself.  Bad news if you don’t.

Social support may protect telomeres and protect against depression and biological aging

Social support may protect telomeres and protect against depression and biological aging

Teleomere takeaway.

Depression is bad for your life. It is a serious disorder with potentially serious repercussions. Get it treated. Eat well, exercise and care for your social relationships. It may protect you from depression and protect your telomeres too.

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Phillips AC, Robertson T, Carroll D, Der G, Shiels PG, McGlynn L, & Benzeval M (2013). Do symptoms of depression predict telomere length? Evidence from the west of Scotland twenty-07 study. Psychosomatic medicine, 75 (3), 288-96 PMID: 23513237

Boccardi V, Esposito A, Rizzo MR, Marfella R, Barbieri M, & Paolisso G (2013). Mediterranean diet, telomere maintenance and health status among elderly. PloS one, 8 (4) PMID: 23646142

Ornish D, Lin J, Chan JM, Epel E, Kemp C, Weidner G, Marlin R, Frenda SJ, Magbanua MJ, Daubenmier J, Estay I, Hills NK, Chainani-Wu N, Carroll PR, & Blackburn EH (2013). Effect of comprehensive lifestyle changes on telomerase activity and telomere length in men with biopsy-proven low-risk prostate cancer: 5-year follow-up of a descriptive pilot study. The lancet oncology, 14 (11), 1112-20 PMID: 24051140

Kim JH, Ko JH, Lee DC, Lim I, & Bang H (2012). Habitual physical exercise has beneficial effects on telomere length in postmenopausal women. Menopause (New York, N.Y.), 19 (10), 1109-15 PMID: 22668817

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Masters Women's Health: Does low estrogen make women unresponsive to anti-depressants?

Depression may be caused by poor Serotonin handling

Don't let the blues get you down.  Get a womens power shirt instead.  This beautiful shirt features Botticelli's birth of spring expressing herself effortlessly with a set of 50 pound kettlebells.

Don’t let the blues get you down. Get a womens power shirt instead. This beautiful shirt features Botticelli’s birth of spring expressing herself effortlessly with a set of 50 pound kettlebells.

Depression stinks.  It hurts.  And it hurts others too. Taking care of yourself, and your moods, is important.  A positive outlook and sense of optimism can carry you a long way.  And it will help you bring along those you care about.  This article reports on some very interesting research on depression and hormones.  It is especially interesting for women whose hormones are shifting.  (in peri-menopause or menopause.)  Estrogen may be important for serotonin signalling.  Low estrogen may make it difficult for some women to respond to anti-depressants.

First, a little background:

  • Serotonin is a neurotransmitter
  • Serotonin allows neurons to communicate with each other.  And sometimes help produce emotions.
  • Depression in some people may be caused by too little serotonin
  • Selective Serotonin Re-Uptake Inhibitors (SSRIs)  work by keeping serotonin active and keeping nerves functioning well.
  • Prozac, Zoloft, and Citalopram are examples of SSRIs.

There are differences in Serotonin Receptors

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To hell with anxiety. Who cares when you’re wearing a WODMASTERS power woman shirt.

Neurotransmitters are chemical messengers.  They travel from one neuron to another by docking at a receptor.  The receptor is a molecule that is designed especially for its transmitter.  Serotonin needs a serotonin receptor if it is going to work.   The shape of the receptor is very important.  But not every person has the same receptor shape.  There are some people whose receptors don’t seem to fit as well.  And they are more likely to suffer from depression.  And anxiety.

Estrogen and Progesterone may be needed for SSRIs to work

 

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Estrogen and progesterone influence the serotonin system including serotonin receptors.  One of the genes responsible for the serotonin receptor is called 5HTT.  So far it looks like you can have either a “short”  version or a “long” version.  The short version (s-5HTT) looks like the problem version.  Monkey have similar systems.  Like Crossfit women.  Researchers used monkeys to see how important estrogen and progesterone are the response to SSRIs.   Monkeys with the shorter gene for the serotonin receptors did not have as strong a response to SSRIs.  Monkeys with low estrogen and low progesterone were the least responsive.  Crossfit women too?

Take away for CrossFit Masters Women and all Women

CrossFit Shirts for women with low and high estrogen

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If you are post-menopausal or hovering around that neighborhood you may not respond well to SSRIs.  Especially if you have the short version of the serotonin receptor gene.   This is one reason why hormone replacement therapy might make some women less depressed.  If you are on SSRIs and they are not working go see a doctor who knows his or her stuff.  A psychiatrist will know more than a family doctor.  Don’t be embarrassed.  CrossFit Women shouldn’t get embarrassed.  Embarrassment stinks.

Michopoulos V, Berga SL, & Wilson ME (2011). Estradiol and progesterone modify the effects of the serotonin reuptake transporter polymorphism on serotonergic responsivity to citalopram. Experimental and clinical psychopharmacology, 19 (6), 401-8 PMID: 21843009

CrossFit WOD 13.3

Eat your vegetables or you'll get depressed.

CrossFit Diet: High Tomato intake help keep you from getting down, blue or depressed.  Which a lot of us might be feeling now that the CrossFit Open is over.

A recent study shows a strong relationship between high tomato intake and a low rate of depression.  People who eat a lot of tomatoes are less likely to depressed than people who eat other types of vegetables.  Those who are depressed tend to eat fewer vegetables than other people.  Of course it may be that people who are depressed are feeling too blue to eat much.  Or are feeling too blue to take the trouble to make a salad.  Or it may be that nutrients in vegetables, such as anti-oxidants, help preserve a positive state of mind.  One earlier reader suggested:  “Italians eat a lot of tomatoes.  Italians are a fun-loving bunch.  Germans do not eat a lot of tomatoes.  Germans are not a fun-loving bunch.  It is being Italian that saves people from depression.”  This is pretty good logic.  However, in this study all of the research subjects were Japanese.

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CrossFit Nutrition Expert Dabney Poorter (right) with friends

Improve your CrossFit Diet: Eat your vegetables or you’ll get depressed.

Finish your tomatoes or you’ll get depressed may be a better dinner table admonition. Low anti-oxidant intake is strongly associated with risk of depression.  Anti-oxidant intake seems to help.  What is very interesting about the new study is that tomatoes seem to be more protective than other vegetables.  Tomatoes contain several anti-oxidants.  However, they are especially high in lycopene.  Lycopene may be the strongest carotinoid anti-oxidant.  High lycopene intake also seems to reduce risk of some cancers. Throw a few tomatoes into your CrossFit diet.

Take home for CrossFit Nutrition:

Take home message for CrossFit and Nutrition

Condensed version

Read this for CrossFit and Nutrition.

Kapoor S (2012). The emerging anti-neoplastic effects of lycopene: beyond its role in prostate carcinomas. Maturitas, 73 (4) PMID: 23067956
Niu K, Guo H, Kakizaki M, Cui Y, Ohmori-Matsuda K, Guan L, Hozawa A, Kuriyama S, Tsuboya T, Ohrui T, Furukawa K, Arai H, Tsuji I, & Nagatomi R (2013). A tomato-rich diet is related to depressive symptoms among an elderly population aged 70 years and over: a population-based, cross-sectional analysis. Journal of affective disorders, 144 (1-2), 165-70 PMID: 22840609