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  • Ask a biochemist.

    I've enjoyed answering a number of other questions about biochemistry in other threads, so I thought that I'd offer my modest expertise in biochemistry to anybody who has a question. I may know the answer to your question, but if I don't, I'll check the literature to see if anybody does. If nobody knows, I'll speculate wildly! A good time for all, to be sure.

    So be my guest, is there something YOU'VE been wondering? I'll do my best to keep answers simple (even at some slight cost to strict accuracy), but you're always welcome to ask me for details if I'm overly vague.

    Have at thee, MDA forumites!

    Give me liberty. Exploration of other options will be vigorously discouraged.

    Wondering something sciencey? Ask me in my Ask a Biochemist Thread

  • #2

    Very glad to have you here!

    I read your last thread. How do you think that fructose is messing up insulin sensitivity and causes diabetes whereas, according to you and others, glucose isn't what messes it up in the first place...? Ingesting glucose makes a person secrete insulin whereas fructose doesn't. I know fructose causes glycation and all that nonsense but how does it make you fat and insulin resistant? Why do you say that small amounts of it are okay (I have heard this from Dr. Eades, too)?


    • #3

      How does fructose mess up insulin sensitivity? It's a tough question, but I'll provide a couple of the popular explanations since it's not yet entirely clear.

      First, fructose metabolism (as opposed to glucose metabolism) bypasses some important feedback regulation mechanisms which would otherwise make sure that the buildup of downstream products would slow down the processing of the reactant (fructose) upstream. This leads to a load of a variety of compounds whose net effect is "make lots of trigs". Some of the fatty acids, however, aren't properly assembled because they've built up to levels that your enzymes can't keep up with, so fatty deposits accumulate in your liver, interfering with function.

      Another problem is that fructose consumption changes the expression of a number of proteins (most notably GLUT5) which regulate normal glucose metabolism, altering your body's capacity to respond to otherwise harmless boluses of glucose.

      Yet another is that high levels of fructose promote polyol (highly polymerizeable alcohols) and AGE formation, causing both "gumming up" of important proteins and chronic inflammation.

      Once the liver ("grand central station" of the body as Stephan Guyenet so aptly put it) is screwed up, none of the various systems in the body are talking to each other properly. If the liver ain't happy, ain't nobody happy. Voila, insulin resistance.

      By contrast, although glucose certainly causes insulin secretion, in the absence of damage, this simply causes storage of the glucose as fat and insulin levels quickly return to baseline, allowing the stored fat to be drawn upon for energy. No problem there. Of course, there are things which sometimes hitch a ride with gluten like some gluten peptide fractions which can cause all sorts of problems, but glucose itself (at least in my opinion, which is worth what you paid for it) isn't necessarily the originator of the issue.

      Small amounts of fructose intake essentially act as mild stressors for the regulatory systems in your liver and elsewhere, causing the body to compensate by increasing it's sensitivity to and capacity to properly dispose of glucose. Too much, and you overwhelm your ability to beneficially over-compensate and you just kick the crap out of your liver.

      There's a lot more to it, of course, but I don't think I've done the subject too great an injustice.

      Give me liberty. Exploration of other options will be vigorously discouraged.

      Wondering something sciencey? Ask me in my Ask a Biochemist Thread


      • #4

        I would like to know in detail what caffiene does to your body? like i have read that it produces cortisol.


        • #5

          I've a couple of problems that I've been struggling to explain:

          I've been strength training (very high weights, low reps(max of 5) with 3-5 minutes rest between sets) for a number of years and have read many comments suggesting that carbohydrate intake is unnecessary provided you are eating sufficient protein (and fat) and allowing at least 48 hours to replenish glycogen from protein.

          In my experience there appears to be a wide variation in individual response to the above diet, whilst following a genuinely very demanding strength based routine. Some seem to flourish, others like me, are forced to resort to carbohydrates (losts of leafy veg and some starchy carbs to increase the carb intake).

          After trying even high protein intake ( >3 gm/lb LBM )

          I've been unable to recover between workouts and have gradually increased carb consumption to around 150gms/day, whilst maintaining high protein and majority of kcals from fat.

          This forum frequently has people expressing support for both approaches.

          Are these different dietary responses simply because I (and others) have failed to adapt to a high fat/protein diet ?

          2nd question:

          I've had a number of conversations with strength trainees who eat extremely high carb and protein (and negligible fat). One in particular is differentiates between carbohydrate and sugar, explaining that his high carb diet (think > 1000 gms carb day - thats carb content of food, not the weight of the food itself) does not promote body fat gain in the absence of dietary fat.

          I thought all carbs were eventually processed as sugar (accepting the differences between glucose and fructose) ?

          Is he correct re a v high carb diet not being fat promoting in the absence of fat, provided you're in an approximate energy balance ?

          Thanks for any insight you can offer.


          • #6

            How beneficial are probiotics to a normal primal person, and how do they help?


            • #7

              I about choked seeing the word "polyol" as an unwanted product of fructose consumption.

              Polyol is a synthetic lubricant for car air conditioning systems!


              • #8

                What a gracious and exciting offer. Thanks, MG! The nerds are grateful.

                We've discussed this question here before, but to no definitive end:

                Is it better to eat carbs alone, or with fat/protein?

                It's my understanding from the Eades (Protein Power) and others that a combination causes a greater insulin spike than carbs alone. However, we're often advised to slow the absorption of carbs by eating them with fat/protein (butter on the sweet potato, nuts with the apple, etc.)

                So which is it? Does it even matter in a person who has a healthy metabolism and is eating 50-100g carbs per day, mostly as veggies?

                ETA -- Just read your fructose explanation above. Very helpful, thanks!

                Nightlife ~ Chronicles of Less Urban Living, Fresh from In the Night Farm ~ Idaho's Primal Farm!

                Latest post: Stop Being Stupid


                • #9

                  Why is it that when somoneone switches from eating little fat to lots of fat, they tend to feel sick? I remember reading something about compromised bile production, is this the case?

                  Stabbing conventional wisdom in its face.

                  Anyone who wants to talk nutrition should PM me!


                  • #10

                    Oooo goody goody!

                    1- What are your thoughts on vitamin D (if that's not too vague)? As in, do high level supplements help the body, or are high plasma levels of vitamin D merely a marker for a healthy system? In which case, adding extra vitamin D into the system may unbalance and upset things?

                    2- Oxalates. Having just read a WAPF article here is there any role for oxalates in health / weight loss? Maybe that's phrased wrong. It boils down to "Do I need to watch intake?" - I eat a fair amount of high oxalate food according to that list.

                    3- What is the biochemical equivalent of a boot up the arse so I stop succumbing to my sugar addiction...?

                    (If you can answer that then you deserve a Nobel!)

                    Thank you very much


                    • #11

                      MG, thanks for the offer! Here are my top two questions.

                      1) To what extent can the body store dietary fat as adipose tissue in the absence of dietary carbs? In plain language, can humans gain significant body fat on a VLC diet? I've seen both points of view on this forum and would really like to know.

                      2) What are the metabolic effects of sugar alcohols like xylitol, sorbitol, and maltitol? There's the famous laxative effect, but surely there must be something else at play, at least some kind of skewing of intestinal biota towards the strains that can tap this fuel source.

                      I could grill you all day with questions but I will restrain myself to those two for now.


                      • #12

                        Thank you so much for your generous offer, and I hope you're not being overwhelmed by the questions you've generated.

                        I've got two questions dealing primarily with fats.

                        1) I have a hard time explaining fat metabolism to people when trying to explain why eating fat won't make you fat. So if you could please describe what the body does with dietary fats with an emphasis on why they do not immediately form adipose tissue in the body.

                        2) I've seen the hypothesis quite a bit that the body stores excess toxins (that is, beyond what it can filter out and excrete) in adipose tissue as a protective measure. I haven't been able to confirm this anywhere, though. Is there any validity to this theory? If so does the body also store nutrients in a similar manner if dietary intake is abnormally high for a brief time, in order to utilize them later.

                        Thanks again for answering all these questions.


                        • #13

                          @Darthash Caffeine works principally by virtue of the fact that it (and it's buddy found in chocolate, theobromine) looks a lot like the business end of adenosine. Adenosine is a compound composed of a ribose sugar and an adenine nucleic acid, both of which are most typically found making up part of our RNA and DNA. Adenosine levels help the body to keep track of how much excitement/available energy is necessary by rising when we need to calm down (or at least when the body THINKS we do).

                          Since adenosine is used to signal for a wide variety of processes, it's tough to tell you about specifics of what caffeine's mimicking it does (although if you REALLY care, we can discuss it), so just think of it in two ways:

                          1) Sometimes there are proteins which break down adenosine normally, but whose active site (the place where most of the actual chemistry happens, not that the other bits aren't important in less obvious ways) will allow caffeine to enter. When these enzymes are what's known as "highly substrate specific", even the slight differences between similar molecules can prevent the normal chemistry from occurring. Normally the first step in breaking down adenosine is pulling off an amine (NH2) group, but caffeine has a methyl (CH3) group in that spot, and methyl groups are tough little buggers. Thus, you don't break down adenosine like you should.

                          2) There are other proteins which sense levels of adenosine which caffeine can sometimes fit into. When it does, it may (depending on the protein) cause the conformational change necessary to signal "adenosine here", or it may just hang out in the active site, preventing adenosine from being sensed. Either way, adenosine levels are sensed as something other than they are.

                          The net result is that the body puts itself in a heightened state of alert, releasing extra fat from your adipocytes, but also raising cortisol levels in preparation for a fight or flight decision.


                          I'm going to have to keep these shorter if I want to get to all of you.

                          @ andrewc

                          Variations in individual workout routine and genetic predispositions make it difficult to say just what might be happening to you, but you're not alone in recovering faster when you have more carbs in your diet. Why? It could be a lot of things; not enough calories, expecting glycogen repletion to be more rapid than is possible under a VLC diet, or even psychological dependence (how long did you internalize the "carbs are fuel" notion before you went primal? Years, I'm sure). Self-experimentation to find your macronutrient ratios is key, since we frequently CAN'T disentangle the thicket of confounding variables like we'd wish. One thing to note, however, is that VLC diets with periodic carb feeds cause "glycogen supercompensation" -- the storage of MORE glycogen than you would be capable of under consistent carb intake.

                          As far as "eat all the carbs you see as long as there's not a drop of fat, and you won't gain weight" goes, it's hogwash. When you have tons of glucose enter your system, your liver first makes glycogen. When that runs out, it checks blood glucose levels and puts out as much blood glucose as it thinks you'll be able to handle (this may be inaccurate if you have problems with insulin sensitivity). After that, the glucose doesn't hang around. It gets converted to, guess what, FAT! Now you have lots of fat AND a hormonal environment conducive to its storage. At this point, your body doesn't much care whether or not the fat was endogenous (made from sugars) or exogenous (from dietary fat). Sure, active -- and more importantly, insulin-sensitive -- young people may easily tap the fat that they're storing (so they don't "get fat"), but rest assured they are storing it.

                          Give me liberty. Exploration of other options will be vigorously discouraged.

                          Wondering something sciencey? Ask me in my Ask a Biochemist Thread


                          • #14

                            @ Brewtality

                            Probiotics are modestly beneficial to someone eating properly (not tons of fermentable carbohydrate in this case), but are of great benefit to people with depopulated or overpopulated (with the wrong beasties) guts. Periodic intake of a suite of good beasties helps make sure that there's some diversity in your gut and no one group gets too prevalent. For example, too much Heliobacter pylori and you get cancer, too little -- it's now emerging -- and your immune system suffers. Most of the bugs in a probiotic fail to adhere to the intestinal wall (or die in their acid bath on the way in), but a few get a toehold and start raising families.

                            @ Barbeygirl

                            I'm inclined to tell you that the slowed gastric emptying and increased satiety (thus causing fewer carbs to be eaten in the first place) are worth any insulinergic effect the proteins may have. When sugar is parceled out more slowly, the area under the insulin curve tends to be smaller anyways. Besides, insulin SPIKES aren't bad in the absence of pathology, CHRONICALLY RAISED insulin is bad.

                            And, as you suspect, this is pretty much a moot point in someone eating ~100g carbs a day. You're just not getting much of an insulin response to that, for a variety of reasons I'll enumerate if you care.


                            Much of it has to do with the fact that the enzymes responsible for getting fat where it needs to go and breaking it down (mostly the first) aren't being expressed highly yet, so you're having a tough time getting energy where you need it and moving the fat along through different parts of the system (not enough bile salts in your gut included). You haven't needed them this much before, and the body abhors waste! As you sustain the different macronutrient ratio, your body adjusts, pulling resources from making proteins that deal with sugars and allocated them to fat metabolism. This is an example of the "gene reprogramming" that Mark talks about.

                            Give me liberty. Exploration of other options will be vigorously discouraged.

                            Wondering something sciencey? Ask me in my Ask a Biochemist Thread


                            • #15

                              @Molecular Grokologist

                              Appreciate your response.