Tag Archives: folate

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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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

Iron Deficiency, Anemia and Athletic Performance

Iron deficiency may slow down athletes, impair training and just making working out harder than it needs to be.

The Iron part of anemia, iron deficiency and athletes

Iron is important for athletes as well as everyone else.   Iron is needed for formation of Hemoglobin.  Hemoglobin is the molecule in blood cells that transports oxygen through blood.  People who have low levels of red blood cells are said to be anemic.  Anemia can be caused by many different things.  This article, however, will focus on anemia caused by nutritional deficiency.

Crossfit sports anemia Iron deficiency
A crossfit athlete trains for the games. Is iron deficiency hurting her performance?

Iron deficiency can slow you down and make your workouts harder and more frustrating than they need to be.   People who are iron deficient (or anemic) don’t carry oxygen efficiently.  The heart has to work harder to get oxygen to tissues.  Low oxygen can also cause “poop out” (just too tired to continue the workout).  No need to mention this . . . but . . .   an iron deficient person is not likely to compete well either.  Anemia is most common in women of reproductive age. Recommended intake of iron is 8mg/day for men and post-menopausal women.  It is 18/mg/day for women who are menstruating.  Iron deficiency anemia (anemia not caused by blood loss, injury, illness of metabolic disorder) is highest among women of reproductive age.  It is uncommon in young men and boys and more common in people over 50.  About 7% of masters adults may have iron deficiency anemia. (Looker et al. 1997)

The athlete part of athletes iron and nutrition

There have been a number of studies of iron intake and exercise performance in animals and in people.  Performance related studies have looked at work performance, fatigue, endurance, oxygen use and heart rate (McClung & Murray-Kolb2013)   Iron supplementation has been associated with:

Anemia, Iron deficiency and Athletes
A crossfit athlete fatigues during the crossfit games. Fatigue increases risk of injury.
  • Increased maximal exercise performance
  • Increased VO2 max (maximal oxygen consumption
  • Lower heart rate
  • Less fatigue
  • More voluntary activity
  • Improved work performance
  • Improved performance on fitness tests
  • Increased energy expenditure

Intense training can lead to anemia.  The popular term for training-induced anemia is Sports Anemia.  Possible causes are intestinal bleeding, iron loss through perspiration, inflammation and a generally faster rate of body iron turnover.    Many athletes (especially older athletes) use ibuprofen to cope with muscle soreness and aches and pains from injuries.  Chronic use of aspirin and ibuprofen can increase risk of iron deficiency because they can cause stomach bleeding.

Iron deficiency can cause some cognitive problems too.  These include spatial ability, attention, memory, executive functioning and planning. These abilities are important in everyday life.  They are also abilities that are essential to training and competition.

The nutrition side of athletes, iron and nutrition

Iron-rich foods include:

  • red meat
  • fish
  • poultry
  • beans
  • dried fruit
  • whole grains
  • chard
  • spinach
  • molasses (black strap style)

Other nutritional deficiencies can also make you vulnerable to iron deficiency even if you are getting enough iron.  Vitamin C and Folate are important too.  Low vitamin B12 also increases risk of anemia. There are a lot of interactions among Vitamin C, Vitamin B12, and Folate that are still poorly understood.  High folate combined with low B12 increases the risk of anemia and risk of cognitive impairment in older people.  Normal B12 and High Folate, on the other hand, protect against anemia and cognitive problems (Morris et al. 2007).  Annoying that there no simple answers.  The best strategy seems to be to eat a varied diet

Take Away

Use pain relievers in moderation.  Consider an iron supplement and make sure you are getting enough folate and vitamin C.  Don’t over do iron intake.  There is no evidence that extra iron will help you if you don’t need it.  Too much iron can cause damage on its own.

 

Andrea Kirk, MSc. PhD is a toxicologist affiliated with the University of Texas at Arlington’s Department of Chemistry and Biochemistry and the University of North Texas Health Sciences Center‘s School of Public Health.  Dr. Kirk does research on human exposures to environmental contaminants and micro-nutrient intake and excretion.  She is also a former whitewater, dog-sledding, ice-climbing instructor and back-country ranger turned box rat.

 

Looker, A. (1997). Prevalence of Iron Deficiency in the United States JAMA: The Journal of the American Medical Association, 277 (12) DOI: 10.1001/jama.1997.03540360041028

Morris MS, Jacques PF, Rosenberg IH, & Selhub J (2007). Folate and vitamin B-12 status in relation to anemia, macrocytosis, and cognitive impairment in older Americans in the age of folic acid fortification. The American journal of clinical nutrition, 85 (1), 193-200 PMID: 17209196

McClung JP, & Murray-Kolb LE (2013). Iron nutrition and premenopausal women: effects of poor iron status on physical and neuropsychological performance. Annual review of nutrition, 33, 271-88 PMID: 23642204

Pasricha SR, Low M, Thompson J, Farrell A, & De-Regil LM (2014). Iron Supplementation Benefits Physical Performance in Women of Reproductive Age: A Systematic Review and Meta-Analysis. The Journal of nutrition PMID: 24717371

Folate, Cardiovascular disease, migraine, depression and MTHFRs

What is a MTHFR?

MTHFR is a gene.  It is a section of DNA that is responsible for producing an important enzyme.  Enzymes are proteins that drive many biochemical reactions.  Enzyme function is essential for your function as a living entity.  MTHFR is also pronounced (Mother @#$!% by graduate students.  And by younger faculty when they think tenured faculty are not listening.)    The enzyme is called Methylenetetrahydrofolate reductase.  It is key to converting folate (Vitamin B9) to a form that the body can use.

If you had no methylenetetrahydrofolate reductase you would be screwed.  Fortunately this is extremely rare.  Possibly because few would survive long enough to be born.  However, life being complicated . . . there are several different forms of the MTHFR gene.  The different forms produce slightly different kinds of enzyme.  The “normal” form is found in most people.  About 70% of the general population. The other 30% have mutations. Chances are high that someone you know is a mutant.  You may be a mutant too.   And there are different kinds of mutants.  “Normal” has two copies of the gene that makes high function enzyme.  Someone could have one normal and one mutant.  This person would make less high functioning enzyme.  But more than someone with two mutant copies.  About 10% of the population is thought to have two mutant copies.  There are also different types of mutations.  So there is probably a range going on here.  In terms of how much methylenetetrahydrofolate reductase is circulating in people.

What does it mean health-wise for MTHFR mutants?

MTHFR mutants can’t convert folate to its useable form as well as MTHFR normals.  They are more likely to be folate-deficient.  This can lead to greater risk of some birth defects.  For example: spina bifida and anencephaly. (not having a brain).  Mutants are much more likely to get migraine headaches.  The kind of headache with aura.  They are also more likely to get cardiovascular disease.  Even if they do everything else right.  Other bad things are:

  • More severe forms of schizophrenia (not all MTHFR mutants have this! Or so says a very reliable voice)
  • More likely to suffer from depression
  • Greater risk of high blood pressure
  • Greater risk of pre-eclampsia
  • Greater risk of some cancers
  • Greater risk of birth defects including heart defects and spina bifida

Some good things about being a MTHR mutant are:

  • Less risk of colon cancer
  • Less risk of leukemia

What are the chances that I am a MTHFR mutant?

A lot of research is still being done.  So far it looks like there are 24 different polymorphisms.   So far it looks like people of Mediterranean descent and Hispanics are more likely to have a MTHFR mutation.  General Caucasions are next.  MTHFR mutations seem to be least frequent in people of African ancestry.  See this article (page 12 for a chart).  If you look at the chart you will see that MTHFR mutations are not uncommon at all.  So don’t feel bad if you are one.  You will need to be more careful about heart disease.  If you are a young woman of childbearing age you should make sure your diet contains enough folate.  If you are low in folate AND a MTHFR mutant you may be more likely to have health problems.

Is there anything I can do about my mutation (Does CrossFit fix mutations)?

Possibly yes.  Methylenetetrahydrofolate reductase is only one step in the conversion of folate to its useable form.  There are now folate supplements you can take in which the folate is already partly converted.  These are available by prescription.  Some people are taking them to help combat depression.  It will be interesting to see if such supplements will also control migraine headaches.  And cardiovascular disease.  And birth defects.  Very exciting. Oh.  CrossFit will not help with this.

What about diet? Are people on the Paleo diet protected?

People who have the MTHFR mutation may need more folate than others.  Regardless of what diet they follow.  Increasing folate intake may protect them from heart disease.  And other problems.  Beans and whole grains are major sources of folate.  Fruit, vegetables and liver are good sources too.  People who drink alcohol regularly will need more folate than others.  So will young women.  People who follow the Paleo diet (or Paleolithic diet) may also have low folate intake. That is because the paleo diet excludes grains and beans.  High vegetable intake should help.   The paleo diet is popular with CrossFit athletes.

Here are a few citations. For more check pubmed.

Liu A, Menon S, Colson NJ, Quinlan S, Cox H, Peterson M, Tiang T, Haupt LM, Lea RA, & Griffiths LR (2010). Analysis of the MTHFR C677T variant with migraine phenotypes. BMC research notes, 3 PMID: 20663228

Gong D, Gu H, Zhang Y, Gong J, Nie Y, Wang J, Zhang H, Liu R, Hu S, & Zhang H (2012). Methylenetetrahydrofolate reductase C677T and reduced folate carrier 80 GA polymorphisms are associated with an increased risk of conotruncal heart defects. Clinical chemistry and laboratory medicine : CCLM / FESCC, 50 (8), 1455-61 PMID: 22868813

Khandanpour N, Willis G, Meyer FJ, Armon MP, Loke YK, Wright AJ, Finglas PM, & Jennings BA (2009). Peripheral arterial disease and methylenetetrahydrofolate reductase (MTHFR) C677T mutations: A case-control study and meta-analysis. Journal of vascular surgery, 49 (3), 711-8 PMID: 19157768