Tag Archives: anti-oxidants

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

BREAKING NEWS: Green tea anti-oxidant EGCG may increase cancer risk. TWF!

 Basics: The anti-oxidant EGCG can cause DNA strand breaks and mutations.

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EGCG stands for Epigallocatechin gallate.   Epigallocatechin gallate (ECGC) is a polyphenol found in green tea.  Some people take it as a supplement.  Or it may be part of “green tea extracts.”  Anti-oxidants are thought to protect cells and DNA from oxidative damage. Oxidative damage can occur when one atom or molecule “steals” electrons from important molecules in your body. Cell membranes, for example. Or DNA. When DNA undergoes oxidative damage it may become mutated. Mutations in body cells can lead to cancer. So, protecting your body by taking anti-oxidants seemed to make a lot of sense. No oxidants, no oxidation, no mutations, no cancer. Many people believe(d) that taking anti-oxidants would protect against illness and aging and extend life. The benefits of anti-oxidant supplements now appears to be more complicated that we thought.

Hypoxia study.  Hypoxia can also cause cellular damage
Hypoxia study without anti-oxidants or oxidants.  Hypoxia can also cause cellular damage.  It might also increase cancer risk.  Brain damage for sure though.

Anti-oxidants have had a mixed history when used medicinally.

There are many anti-oxidants.   Vitamins C, A, E and selenium are commonly used as nutritional supplements for their anti-oxidant properties.  And many have assumed that more is better.  As with many other things in life, more is not always better.  Sometimes “more” makes more trouble than less.  Selenium, for example, seems to have protective effects against cancer.  Unfortunately when too much selenium is taken, it can increase the risk of cancer.  One of the problems with taking supplements is that we rarely know how much is too much.  And we almost never know how much is optimal.   Studies of Vitamin A, C and E have also shown signs of creating problems when taken above levels one would normally get eating from food.

EGCG as an inducer of mutations and cancer.

A paper newly released by Nature (Lu et al. 2013) shows how anti-oxidants are able to cause DNA damage and increase risk of mutations. The researchers used epigallocatechin gallate as the test anti-oxidant.  The researchers present their data very clearly and efficiently with minimal interpretation.  They simply report that Epigallocatechin gallate caused DNA damage and increased number of mutations (among other non-good things.)  These results may or may not apply to other anti-oxidants, but they are a good indication that we should exercise caution with anti-oxidant supplements.    There is sure to be a lot of discussion and debate over the results of the Lu study.  And many additional studies are sure to follow.

Anti-oxidants, oxidants and health
It you are feeding your pets anti-oxidants you might want to hold off for a while.

This is a very interesting paper and sure to upset a lot of boats.   ECGC is a powerful anti-oxidant.  Other anti-oxidants may not be strong enough to cause damage.  It was just a year ago that  ECGC was reported to be the most effective anti-cancer chemo protective compound in green tea.  ECGC may turn out to be health protective.  It may turn out to be one of those “nutrients” that is good for you at low levels but dangerous when high.  Its too early to tell.  More research is needed.

Until we know more, eat real food.  Eat a varied diet so you don’t get too much of something that may be harmful.

 

 

Lu LY, Ou N, & Lu QB (2013). Antioxidant induces DNA damage, cell death and mutagenicity in human lung and skin normal cells. Scientific reports, 3 PMID: 24201298

Du GJ, Zhang Z, Wen XD, Yu C, Calway T, Yuan CS, & Wang CZ (2012). Epigallocatechin Gallate (EGCG) is the most effective cancer chemopreventive polyphenol in green tea. Nutrients, 4 (11), 1679-91 PMID: 23201840

Thangapazham RL, Passi N, & Maheshwari RK (2007). Green tea polyphenol and epigallocatechin gallate induce apoptosis and inhibit invasion in human breast cancer cells. Cancer biology & therapy, 6 (12), 1938-43 PMID: 18059161

Masters CrossFit: Does type of workout matter? Is CrossFit, endurance or weight training best?

There are many benefits from fitness.  And many reasons why people enjoy (or subject themselves to) CrossFit Workouts.   Staying in shape.  Looking good.  Masochistic tendencies.  However, on a deeper level regular exercise reduces risk of cancer, diabetes and heart disease.

Current research indicates Fitness may protect us from free radicals.   Free-radicals are major factors in development of disease.  Diabetes, cancer and cardiovascular disease are all conditions where free-radicals are thought to be involved.  Free radicals are oxidizers.  They are molecules that have lost an electron.  These pose problems because they are very reactive.  They grab electrons from other molecules.  Thus “oxidizing” them. They stress cells.  Throw wrenches in the works.  This includes wrench throwing into your DNA.  Imagine a CrossFit workout where someone loses a plate in the middle of a crowded box.   Full of people doing Fran without collars.

Damaged DNA can result in cancer.  Or birth defects.  Free radicals also  damage tissues and organs by damaging cells and increasing inflammation. For example, they can damage pancreatic beta cells and increase risk of diabetes.

What are anti-oxidants?  How do fitness and risk come into play?

Anti-oxidants are agents that protect us from free-radicals.  They neutralize them.  Having enough anti-oxidants reduces risk of chronic disease  Normally we think of anti-oxidants as something we get from vegetables.  Or fruit.  Or supplements.  However, exercise seems to be involved too.

Exercise, anti-Oxidants, Fitness and Risk

Exercise causes a number of changes.    These changes play into the free-radical game.   They are adaptions to the stress of exercise.  When people are getting in shape free radical production increases.   Your body suffers inflammation.  And aches and pains.   This is often seen after a CrossFit Workout.  And in the days following a CrossFit workout.   Especially when people are first getting started.  This is very much like what happens when you get sick with a fever.  This may be why getting in shape sucks so much.   When you are getting in shape (or pushing yourself to a higher level) your body produces more free-radicals.  But is not ready to handle them.  Adaptation to exercise includes increasing production of anti-oxidants.  Once you have adapted you will be producing enough anti-oxidants to protect from free radicals from increased exercise.  You will also have increased protection from other sources of free-radicals.

Does type of workout matter? Is CrossFit, endurance or weight training best?

Animal testing indicates that endurance exercise works best for protection from inflammation and free radicals.  The animals tested were rats.  They were subjected to endurance training, resistance training and combination training.  Hard to visualize. Hopefully more research will be done in this area.   And we will get a better picture of what is optimal for humans.  Weight training (resistance exercise) remains important.  And CrossFit exercises (and high intensity interval training) show very promising results on other aspects of health and fitness.  It seems likely that adaptation to these forms of exercise will produce results similar to endurance training.

References for further reading.

de Lemos ET, Oliveira J, Pinheiro JP, & Reis F (2012). Regular physical exercise as a strategy to improve antioxidant and anti-inflammatory status: benefits in type 2 diabetes mellitus. Oxidative medicine and cellular longevity, 2012 PMID: 22928086

de Oliveira VN, Bessa A, Jorge ML, Oliveira RJ, de Mello MT, De Agostini GG, Jorge PT, & Espindola FS (2012). The effect of different training programs on antioxidant status, oxidative stress, and metabolic control in type 2 diabetes. Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme, 37 (2), 334-44 PMID: 22458821