What the Heck is Oxidative Stress?

I received my copy of the quarterly TCOYD newsletter a few days ago, and was intrigued to find an article explaining oxidative stress. I’d been hearing that term associated with diabetes complications for quite a while now and wondering what the heck the connection was.

The OnTarget blog offers a great core explanation:

“Oxidative stress (OS) occurs when the available supply of the body’s antioxidants is insufficient to handle and neutralize free radicals of different types. The result is massive cell damage that can result in cellular mutations, tissue breakdown and immune compromise.”


Lucky for us, Dr. Irl Hirsch and Dr. Michael Brownlee, Director of the JDRF Center for Diabetic Complications Research, have been studying the causes of diabetic complications for a number of years. The landmark DCCT study provided the first solid empirical evidence that high glucose levels have a direct impact on the development of complications. But how exactly does high blood sugar do its damage? Researchers have identified four biological pathways, all of which may be triggered by oxidative stress, according to Hirsch and Brownlee.

“To make high glucose inside a cell, these four pathways have to be turned on. But the question was, is there a black box in there controlling the whole process? We discovered there is. It’s an overproduction of reactive oxygen species or free radicals, generated because high blood glucose, which is normally burned off in sub-organ of the cell called mitochondria,” Dr. Brownlee explained to me in a recent telephone interview. (plus a lot more scary science-speak, wha?)

“When you have high glucose in the blood, most tissues can ‘close the gate’ and keep the internal glucose levels normal, but certain cells cannot do that, so they get high blood glucose inside the cell, causing damage. These happen to be mostly nerve cells… We’re focusing on focus on intra-cellular oxidative stress, due to the lack of the ability to ‘close the gate’ to glucose.”

Ah, got that. From my layman’s viewpoint, the discovery of a “black box” or “unifying mechanism” that causes complications sounds promising. The first step to curing anything is identifying the exact pathways by which the damage occurs.

So we should all be taking anti-oxidants like vitamin E, vitamin C and beta carotene, right? WRONG. According to Dr. Hirsch’s TCOYD article, human trials have shown no benefit for loading up on these, and doing so may even increase risk for heart attack and stroke.

Instead, current thinking centers on — you guessed it — reducing glycemic variability (our nemesis). “There is currently a huge controversy about how glucose variability and reducing the after-meal spikes may improve oxidative stress,” Dr. Hirsch writes. Some research apparently suggests that reducing high spikes “can provide a better defense against oxidative stress.”

So what does the good doctor suggest for us patient-types? “Using the tools we have at hand!” to reduce BG spikes.

For Type 2s, that would include the drugs Prandin, Starlix, Precose, Glyset, Januvia, and Byetta. For Type 1s, think Humalog, Novalog, Apidra and Symlin. CGM systems can help all diabetics improve their BG control, of course.

Nothing entirely new there — except for perhaps better motivation than ever to keep our post-meal BG levels in check. Yeeeooow.


16 Responses

  1. Sarah
    Sarah February 7, 2008 at 8:02 am | | Reply

    I disagree 100% with the “tools at hand” we are told to use. That is B.S.

    All that does is put more money in the pocket of Big Pharma while diabetics die. We all know that injected insulin does not allow for precise enough control of T1.

    Instead, add some supplements to your routine, including some *anti-oxidants*. Obvious really, but since Big Pharma is out to make money off of you, they’d rather treat your complications down the line and say insulin is the solution. It is not.

    What is:

    -Benfothiamine (Synthetic B1)
    -Vitmain C
    -Omega 3 EFA
    -Anti-oxidant blends
    -Folic Acid

  2. Sarah
    Sarah February 7, 2008 at 8:08 am | | Reply

    Sorry, read the article too fast! Only so much time in a day! Regardless, I think that although in some cases *excess* supplements can do more harm than good, I still feel that the RIGHT amount is beneficial. And Big Pharma would rather have us be ignorant to that fact.

    Think about it…to little or too much insulin is bad…but the “right amount” is good.

    Also, at least one Vitamin E study was flawed. Some of the people in the study were given large amounts of Vitamin E, but they were very ill and at a very high risk of dying anyway. Not all of us are that far gone yet.

  3. Sarah
    Sarah February 7, 2008 at 8:11 am | | Reply

    One more thing:

    Antioxidants become oxidants at very high levels. Which is the opposite of what you want.

    Perhaps they also need to be applied in a balanced ratio with other supplements to be effective and safe.

  4. Miriam
    Miriam February 7, 2008 at 8:45 am | | Reply

    Hey, let’s not forget about eating veggies! Spinach, broccoli, zucchini, cabbage, etc…All are excellent sources of antioxidants without side effects (except possibly mild gastric)!

  5. Scott
    Scott February 7, 2008 at 9:32 am | | Reply

    Hyperglycemia itself has not been proven to actually cause oxidative stress, rather it is merely a correlation, not a cause. In fact, researchers have found that some items, including cardiovascular disease in type 1 diabetes and neuropathy in type 1 diabetes actually have an autoimmune basis — in other words, the same immune system defect that caused the destruction of the pancreatic beta cells is also the same source of inflammation that helps destroy certain nerves and cardiovascular tissue. For reference, check out the following:

    Increased Monocytic Activity and Biomarkers of Inflammation in Patients With Type 1 Diabetes
    Diabetes 55:774-779, 2006
    DOI: 10.2337/diabetes.55.03.06.db05-1417

    Autoantibodies to Autonomic Nerves Associated With Cardiac and Peripheral Autonomic Neuropathy
    Diabetes Care 28:1959-1964, 2005

    The source of inflammation in type 1 and type 2 diabetes is believed to be caused by different processes, although much more work needs to be done to identify each.

    Finally, with at least 3 major meta-analysis proving it, I find NO conclusive evidence that the use of insulin analogs including Humalog, Novalog, Apidra will do anything to reduce glycemic variability. Symlin may, and CGMS may also, but analogs … the evidence does not support such a claim.

  6. Mark
    Mark February 7, 2008 at 10:16 am | | Reply

    Sounds like it came from the Department of Redundancy Department.

  7. Adam Becker Sr
    Adam Becker Sr February 7, 2008 at 2:01 pm | | Reply

    You write “For Type 2s, that would include the drugs Prandin, Starlix, Precose, Glyset, Januvia, and Byetta. For Type 1s, think Humalog, Novalog, Apidra and Symlin. CGM systems can help all diabetics improve their BG control, of course.”

    Uhh, what about (a) using a glucometer to track our post-meal bg levels and (b) when we find we’ve exceeded our goal levels, cutting back on the carbs? (My goal is to always stay below 140 mg/dl.)

    In my book, dietary control always comes first.

    Adam Becker Sr

  8. WC
    WC February 7, 2008 at 3:42 pm | | Reply

    Come on Adam, how is anyone supposed to make any money off dietary control? WE NEED MORE PILLS!

  9. Windy
    Windy February 7, 2008 at 5:25 pm | | Reply

    I love how you can take crazy complicated biology concepts and explain them in the “lay people” vernacular. Thanks Amy.

  10. Mel
    Mel February 7, 2008 at 5:51 pm | | Reply

    I am learning so much since finding your site! Thanks!

  11. Lauren
    Lauren February 7, 2008 at 9:29 pm | | Reply

    Oxidative stress is also one of the theories of aging — basically, cells wear out/die due to the stresses (ie free radical production) of cellular respiration, which of course involves oxygen. As a med student I have to correct your spelling of “mitochondria.” They are components of the cell always referred to as the “powerhouses,” where energy synthesis occurs.

    I find the gate closure theory interesting; it would explain why nerve cells, which are opening and shutting chemical gates constantly to send signals, are particularly likely to uptake and retain glucose. I’ve never made the connection between nerve cell physiology and nerve susceptibility to glycemic damage.

    Another theory I’ve heard regarding complications involves glycosylation. When too sugar is circulating, glucose adheres to proteins. (The percentage of glycosylated hemoglobin gives us our A1c level.) When sugars stick to proteins, it can interfere with the normal functions of those proteins.

    I’m no biochemist but I love to hear about research like this; understanding mechanisms can bring us closer to the holy grail, prevention.

  12. Lauren
    Lauren February 7, 2008 at 9:38 pm | | Reply

    I also have to agree with Adam’s post above. We have to use the tools we have, and that includes diet. I can’t say I stay away from carbohydrates, because I love them, but I never eat carbs when I know I won’t be able to check and correct my post-prandial BG. I’ll often eat nuts and plain soygurt during the day when I’m busy, since those barely require a bolus.

  13. wschaf
    wschaf February 10, 2008 at 1:50 am | | Reply

    Lauren: IMHO, your hypothesis that the frequent opening of ion channels may have something to with excess glucose accumulation in nerve cells does not seem likely. Look them up [I know you're pressed for time]. The channels are specific for one type of ion with a limited size, while glucose is much bigger. If I remember correctly, too much extracellular glucose gets absorbed by nervous tissue, because the “gates” [glucose receptors] cannot be closed as effectively – actually down-regulated or fewer thn normal produced. Nerve cells normally survive with glucose as its only energy source, so excess glucose gets absorbed and some of it gets converted to sugar alcohols which accumulate, causing the nerve cells to swell and lose some function, which would allow more glucose to cross the cell membrane as it loses some integrity. It’s probably even more detailed than this brief description.

    You are quite right about added glucose to proteins: Glycosylation = loss of functions.

    One thing needs to be added about food sources of antioxidants. The common ones that we know the most about, because they are essential, are vitamins C & E. Then there are others that you may have heard about: beta-carotene, lycopene, resveratrol, coenzyme Q10, glutathione; a number of enzymes the body produces; and finally whole families of polyphenols, flavinouds, tannins etc which are little known and understood. Most of these are supplied from plant sources – so EAT A WIDE VARIETY OF VEGGIES.

  14. RKB
    RKB April 3, 2009 at 12:36 pm | | Reply

    What an interesting discussion. I just made this same comment at some other blog but it might also be helpful here:
    People who are following this topic may also be interested in Eng3, they seem to be improving the lives of people suffering from chronic fatigue syndrome and other problems with a device called Activated Air. They have some good information at their website and it is worth looking over their blog posts, this is the main site http://www.eng3corp.com

  15. affiliate
    affiliate February 25, 2010 at 1:38 am | | Reply

    made this same comment at some other blog but it might also be helpful here

  16. Rick Allwright
    Rick Allwright May 3, 2014 at 10:38 am | | Reply

    Protandium has been proven to reduce oxidative stress by 40% and people with diabetes are having amazing results.

    Everyone needs to be taking this amazing supplement. Check it out, see my website: http://www.mylifevantage.com/rickallwright

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