Friday, November 2, 2012

My AHS 2012 Talk Is Now Up! Oxidative Stress and Carbohydrate Intolerance

by Chris Masterjohn, PhD

My talk at the 2012 Ancestral Health Symposium, "Oxidative Stress and Carbohydrate Intolerance," is now freely available online! Enjoy!

Chris Masterjohn — Oxidative Stress & Carbohydrate Intolerance: An Ancestral Perspective from Ancestral Health Society on Vimeo.

Read more about the author, Chris Masterjohn, PhD, here.

30 comments:

  1. Fantastic talk, Chris.

    Like I mentioned on your article about this, it would be great if you talked about all of the mechanisms that contribute to nutrient overload that we know about, and some dietary factors that help prevent it in the first place. Maybe for 2013? The greatest talk ever??? I think so.

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    1. Thanks Stabby! Good idea! I'll try!

      Chris

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    2. For the last year or so it has been in my head that you were writing a book on cholesterol. Did you ever say that? Is that accurate? Am I experiencing wishful confabulations? :-)

      Also what do you think of l-arginine in preventing atherosclerosis in rabbits and other animals with hypercholesterolemia and its implications for humans?

      http://circ.ahajournals.org/content/96/4/1282
      http://www.ncbi.nlm.nih.gov/pubmed/8294700
      http://www.ncbi.nlm.nih.gov/pubmed/16157883
      http://www.pnas.org/content/102/38/13681.full

      I know you have talked about magnesium and cocoa, and think that endothelial nitric oxide is important. And there is also exercise and omega-3s combined with antioxidants that have some beneficial effects in these models. Of course nobody has shown complete prevention of atherosclerosis in the cholesterol-fed rabbits for long durations, but what if they put together all of the interventions? Maybe they could have a happy-rabbit-health-club study where all of the interventions known to help are used? If the serum LDL remained astronomically high but atherosclerosis was prevented that would cast a lot of doubt on the view that serum LDL was the most important factor in atherogenesis.

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    3. one of those was in monkeys*

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  2. This is very good, clear ideas.
    I don't think ROS travel at random or spread at diffusion rates, I suspect most are targeted in some way; there are streams, or currents.
    How else could catalase have such a high activity rate? A batter with a high hit rate needs an accurate pitcher.

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  3. Is there a way to get this in audio form?

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    1. Hi Meghan,

      The easiest way to do that would be to press play but not watch the video. If you want to download it, you can probably get some kind of add-on to a browser for that. Firefox Download helper might work -- it does for youtube, and you should be able to convert it to an mp3. I'm not sure of the details though.

      Chris

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  4. Chris, great talk. thanks. I have a few questions:

    you have mentioned adequate protein? Is there any way to test for this or define it?

    and also, you've mentioned beef broth for the glycine, is eating foods made with gelatine the same thing?

    thanks.

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    1. Hi Anonymous,

      Thanks!

      According to available evidence in humans, which I would consider preliminary, 1 gram of protein per kilogram (~2.2 pounds) of body weight, including 24 milligrams per kilogram body weight is sufficient. For someone weighing 75 kg, this would be 75 grams of protein and 1.8 grams of sulfur amino acids.

      Theoretically, gelatin should provide all the benefits of glycine that you would get from bone broth. There might be other beneficial things in bone broth though, so I wouldn't consider them exactly equivalent. If the choice is between using bone broth and gelatin, I would use bone broth; if it is between gelatin and nothing, I would use gelatin.

      Chris

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    2. Chris, thanks for your reply. what do you think about fasting? meaning, if I fast one day, do I need to double the protein intake the next?

      also, you said that IR is a desease of too much energy, but what if i eat mostly fat, very low carb, adequate protein, but extra fat, can I get IR?

      thanks.

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  5. Hi Chris,

    I really enjoyed your presentation: fascinating topics, great analogies, and clearly presented in an engaging way. I learned a lot, so thank you.
    In addition to this, my compliments to the AHS crew: the video is well lit and sharp, the slides were overlayed at the appropriate moments, and the audio was clear.

    I also have a question: what is your take on the role of thiamine in AGEs, glucose tolerance, and insulin resistance?
    To me it seems that when GSH gets depleted due to oxidative stress, and methylglyoxal goes up as a result, methylglyoxal reduces glycolytic flux and thereby diverts glucose to the pentose phosphate pathway (PPP). This can produce NADPH which can regenerate GSH. So, methylglyoxal appears to regulate oxidants from two sides: reducing the creation of new oxidants (glycolysis↓) and removing existing oxidants (PPP↑ → GSH↑).
    However, when there is insufficient thiamine, the PPP enzyme transketolase cannot do its job, hampering the PPP's ability to fully oxidize glucose 6-phosphate to CO2 and NADPH. In that case both glycolysis and the pentose phosphate pathway become unavailable routes for glucose, causing the cell to stop consuming it, regardless of insulin levels → insulin resistance.


    John

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    1. Hi John,

      Good points. The fates of glucose are more complex than that, though, and depending on the tissue you will often have activation of the polyol pathway during hyperglycemia and NADPH is net lost. An oral glucose tolerance test depletes GSH in erythrocytes, and the loss of NADPH could be part of that. MGO itself decreases GSH simply because it binds to it. There are a lot of pathways to account for! But I think you are right that thiamine is important for the reasons you point out. Moreover, thiamine is lost in the urine in diabetes. Most likely diabetics should supplement with high-dose thiamine as a matter of course -- it has been shown to help with kidney problems I think.

      Chris

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    2. Thanks for your answer Chris.

      Yeah, the "good" old polyol pathway. It would of course suck if the NADPH from the pentose phosphate pathway would be used to turn glucose into sorbitol or fructose.

      About thiamine: I think I also came across a study where it seemed to prevent diabetic kidney damage. For sure there is an in vitro study that showed reduced methylglyoxal in red blood cells when incubated with high thiamine. Also, a study in rats found that high thiamine prevented diabetes induced increased cholesterol and triglycerides. I even came across a study suggesting that rats seemed to avoid sucrose when they were thiamine deficient (probably rats with biochemistry knowledge).

      I can dig in my bookmarks for my thiamine references if you like. Just let me know.

      Speaking of references: can you share the reference to the study you mentioned in your presentation, with the manipulated "limitless" fat cells that allow obesity without metabolic derangement?


      John

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  6. Hi Chris,
    nice talk indeed! and thanks to the people of AHS for the good work. I have a question: you talk about a shift toward oxidative stress in presence of an energy excess; do you think the same could apply also in presence of a prolonged energy defect? (i.e. ipocaloric diet?) thank you
    Igor

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    1. I also have a question. What are your thoughts on a healthy maintenance level of glucose/carb for previously obese individuals and are now lean. Do you believe, generally speaking, in "broken metabolisms"? If so, even for those of us who managed lose the weight to be considered at a very healthy weight?

      I feel in addition to genetic factors there should be more studies involving previously obese people (now lean) in how well they tolerating glucose compared to normal weight/glucose tolerating people.

      http://paleohacks.com/questions/160659/carb-glucose-intolerance-in-formerly-obese-now-lean-individuals#axzz2BtGtcN3P

      thanks,

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  7. Hi Chris,

    Great talk! I had one question: how you would qualify carbohydrate intolerance in clinical terms?

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  8. Insulin resistance is caused by high sodium and low potassium levels. Insulin requires potassium.

    Its impossible to create disease with whole foods. Processed foods cause disease because of their lack of vitamins and minerals.

    So...

    How come when biochemical reactions are mentioned, minerals are never mentioned in the reactions?

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  9. http://high-fat-nutrition.blogspot.com/2012/10/protons-zero-fat_3.html

    Peter at Hyperlipid wrote recently about a zero fat, high starch diet and it is getting a lot of attention. People have transformed his thoughts into a 2 week "Potato Diet" and are losing fat at a rate of 1/2 - 1 pound a day!

    Have you given any thought to the efficacy of a short-term, high starch diet for weightloss?

    Peter says:
    "How about scaling this up to a massive dose of potato induced insulin and limiting dietary fat? Severely limiting dietary fat. And never mind pussy footing around at 40g of mixed carbs and protein. There is a limit to how low FFAs can be driven, and it seems safe to assume that a baked potato or three might just inhibit lipolysis maximally and keep it that low for rather a long time. But if you deprive beta cells of free fatty acids you blunt their ability to secrete insulin. Very, very high carbohydrate diets really ought to be able to inhibit lipolysis to the point where the knock on effect is the inhibition of insulin secretion, provided you don't supply exogenous fat."

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    1. Hi Anonymous,

      I don't really see why the quote you provide from peter about inhibiting lipolysis would help lose weight, but I would think such a diet would cause a spontaneous reduction in caloric intake, so I would be surprised if it didn't lead to weight loss.

      Chris

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    2. http://www.drmcdougall.com/store_starch_solution.html

      This is a whole book about starch-based eating for weight loss and health.

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  10. Nice talk.
    Energy imbalance as the driving force for insulin resistance and oxidative stress. I think that a systems biology approach could be used to model some of these issues. I can see that the feed-back control is, at best, "incompletely described" but systems-type approaches have been used to describe such "messy" systems.

    Any thoughts?

    Aleck Alexopoulos

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    1. Hi Aleck,

      Taking that on is a bit beyond me at the moment, but certainly valuable. Thanks for the thought!

      Chris

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  11. Chris: Hi wonderful presentations here and at WAPF!

    Would there be a mechanism by which amylase directly helps us to metabolize "stress" directly. After listening to your talk Googled and found that salivary Amylase is being used as a marker for sympathetic nervous system activation.

    But I wonder if it could be a direct mechanism for the body to modulate inflammation directly, i.e. phasic vs tonic amylase release In humans this same system would also be recruited to deal with psychological stressors, and not just a post-stress marker. Would this be thru glucose/insulin or something else.

    Some examples:
    Stress reactivity to co-rumination in young women’s friendships: Cortisol, alpha-amylase, and negative affect focus
    http://spr.sagepub.com/content/28/4/469.short
    Chronic stress, salivary cortisol, and α-amylase in children with asthma and healthy children
    http://www.sciencedirect.com/science/article/pii/S0301051107002013
    Experience with the anti-inflammatory enzyme, Fortizyme, in general practice.
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2642443/?page=1

    Anyway this was a quick post T-day Dr Google search.

    I had been wondering if knowing one's Amylase copy number or functionally measuring amylase would help in knowing whether "Safe Starches" really are safe for someone, or directly supplement buccal amylase before meals might be different than say using bitters.

    Rafael G


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  12. Chris, did you know Rich Van Konynenburg?
    He taught me everything I know about glutathione and the methylation cycle; I've just learned of his death.

    http://phoenixrising.me/treating-cfs-chronic-fatigue-syndrome-me/treating-chronic-fatigue-syndrome-mecfs-glutathione-and-the-methylation-cycle/comment-page-1#comment-81347

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  13. Excellent talk... OUCH my head hurts!

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  14. Chris, what do you think of these studies which question the reliability of the Inuit's reputation for having a low incidence of heart disease?

    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC325106/pdf/thij00043-0014.pdf

    http://www.sciencedirect.com/science/article/pii/S0021915002003647

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  15. Sorry to bring you back to an old talk, but I'm new question has come up for me. I understand insulin function in the healthy person, no energy overload. At about 20 minutes into the talk, you discuss the energy overload situation with insulin resistance, and how it affects the tissues differently. I thought that in insulin resistance, adipose cells retained their insulin sensitivity in the face of high circulating insulin, and that is how they continue to store fat. If they closed their receptors to insulin, would they not stop storing sugar and fat?

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  16. Hi Chris, found a great summary article of differential tissue effects of insulin in fasted and fed states, so please don't waste your time on my question - in case any of your readers are interested - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1204764/
    Cannot thank you enough for the clarity of your writing and videos talks

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