Friday, August 19, 2011

Do Carbs Make You Crazy? More About Blood Glucose, Violence, and Mood

I began this series yesterday with a bit of an introduction and some exposure to some differing theories about carbohydrate consumption and mental health (basically they run the gamut from very low carb will spare your mood to you absolutely need carbohydrates for sanity).  I didn't take much of a stand, myself, other than to note that in my personal experience, a bit of healthy fat and protein has kept me from experiencing some of the uncomfortable weakness, tremulousness, and crankiness I had a few hours after sugary meals years ago, when, ironically, Stop The Insanity was in vogue.

(Music - Alexander Borodin, Polovtsian Dances, right click to open in new tab)

I noted in my last post that somewhere between 1966 and the early 1990s, it became very unfashionable for medical professionals to endorse the idea of "hypoglycemia," outside of a super low measured blood glucose level of around 40 or less.  "Relative (or reactive) hypoglycemia" had been consigned to a psychosomatic diagnosis.  So my relative hypoglycemia which predictably occurred at expected physiologic intervals after ingestion of exclusively high-sugar foods or drinks must have been all in my head. :-) In fact, the year before I was born, the American Diabetes Association, the Endocrine Society, and the American Medical Association issued a joint statement on hypoglycemia,  stating that widespread publicity "has led the public to believe that there is a widespread and unrecognized occurrence of hypoglycemia in this country… These claims are not supported by the medical evidence."  The American Dietetic Association stated: "Valid evidence is lacking to support the hypothesis that reactive hypoglycemia is common cause of violent behavior."

However, when blood glucose falls to quite low levels, the body does tend to react rather aggressively in order to prevent death.  Stress hormones, including catecholamines and glucocorticoids, growth hormone, and glucagon are all released.  This high-powered combo would no doubt cause sweating, palpitations, anxiety, weakness, crankiness, and other symptoms traditionally associated with hypoglycemia (but can also occur whenever high levels of these hormones are released for any cause) (1 - amazing paper, by the way.  I highly recommend it).  If the blood glucose falls low enough that the brain is impaired, certainly very bizarre behavior (such as psychosis) can be observed.

How common is such low glucose outside very rare insulin-producing tumors or accidental overdoses of diabetic medications?  Well, actually, in oral glucose tolerance tests (the gold standard is when you are given 50 grams of dextrose after an overnight fast, and then blood glucose is measured continuously for up to six hours - often the absolute nadir is missed if the glucose is not measured continuously, but rather at half hour intervals, as is also common), there is a wide range of glucose nadirs in the blood levels of those tested.  The average level is about 65, but 10% of people fell below 47, with 2.5% of people below 39.  That means that 1 in 40 people could expect to have "true" hypoglycemia in the context of a pure carbohydrate snack after a fast.  This effect can be accentuated by caffeine and alcohol.

However, when one goes around measuring glucose levels of typical human beings eating mixed meals (not participating in oral glucose tolerance tests) levels almost never fell below 70.  In these healthy subjects, levels pretty much stayed between 70-100 all day long, before and after meals, and overnight.  It was a combination of these findings and studies of so-called hypoglycemics whose blood glucose levels did not correlate to symptoms that consigned "relative" or "reactive" hypoglycemia to conservative medical never-never land.  However, in my own case, the symptoms were predictable, and the predictable treatment of switching to a higher-protein, higher-fat, less crappy diet cured it, which I would find odd if it were entirely psychosomatic.  Also interesting and pointing to a physiologic cause is that the symptoms returned for me during pregnancy - where insulin reactions and "relative" hypoglycemia will tend to be of larger magnitude than in the non-gravid state, in order to promote glucose uptake by the growing fetus.

But there are other very interesting correlates between hypoglycemia and behavior and mood.  A researcher named Bolton studied the Peruvian Quolla Indians, who are apparently known as "perhaps the meanest and most unlikeable people on earth." (2) These people, particularly the men, seemed to act out in irrational acts of violence, and also seemed to have very strong sugar cravings.   Bolton happened to do glucose tolerance tests in many of the men, and he noticed a statistically significant correlation between the most aggressive subjects and those who had the lowest blood glucose values during the GTT (3).  Another researcher, Virkkunen, studied men who had committed serious violent assaults.  Their GTTs were also remarkable for higher peak glucose values and subsequently lower glucose nadirs than controls (4).  Folks with antisocial personalities have also been noted to have low blood glucose levels, and, once again, it is important to note that many of these men perpetrated the crimes under the influence of alcohol, which will accentuate the hypoglycemic effect.  Similar studies in the general population show that both men and women whose blood glucose fall more rapidly during a glucose tolerance test will tend to have higher ratings of aggression (5)(6).  In these studies, a glucose level of 63 or lower was strongly associated with the aggressive tendencies.  This is still outside a normal healthy humans' blood glucose range eating normal food, but much, much closer to the normal range than 40.

Wow.  I guess rapidly fluctuating blood glucose does cause behavioral changes… wait a minute, there, buckaroos - as I had noticed in my perusal of the rather badly reasoned behavior/blood glucose/insulin resistance literature (which I will go over in the next post), and which Inthewooo noted in her comment on the first post in this series, these are mere correlations.  Why is the blood glucose changing more rapidly in certain people than others to the same food or glucose stimuli?  Could an underlying mechanism explain both aggression and hypoglycemia?

Virkkunen's more violent reactive hypoglycemics had enhanced insulin response to the oral GGT.  And it has been found that impulsive offenders who act aggressively, particularly when intoxicated, have lower levels of serotonin turnover (measured low levels of the metabolite of the serotonin metabolite 5-HIAA in the CSF (7)). Low levels of brain serotonin are associated with enhanced insulin secretion and a tendency to develop low blood glucose levels.  The data is a bit tenuous, but at least this mechanism makes some sense in the big picture.

Next up - carb craving and chocolate and PMS and Wurtman's rodents!  Women with PCOS, reactive hypoglycemia, hyperglycemia, and mood relationships.  You might be surprised at what the science shows...


  1. I am really finding this discussion quite interesting.

    Oh, "hypoglycemia" is definitely real and it is common. Absolute hypoglycemia is not common but relative hypoglycemia is very common, as common probably as obesity (as the two are clearly related).

    Few decades ago it was vogue to blame everything on "hypoglycemia", which threatened a lot of other ivory tower types and clinicians. If HYPOGLYCEMIA causes schizophrenia, that means refrigerator mothers DONT, therefore I need to discredit this HYPOGLYCEMIA thing or else my theory is no longer competitive.

    The original description of hypoglycemia as a cause of pretty much everything probably isn't correct, but today it is pretty commonly accepted that rises and falls in blood sugar throughout the day - symptomatic of early glucose intolerance and/or an incredibly horrible high carb low fat/low protein diet - is real.

    When discussing the phenomenon of hypoglycemia, clinically speaking there are two main effects of it, which are caused by totally separate mechanisms. All hypoglycemic symptoms can be umbrella'ed under neuroglycopenic, and adrenergic.

    The neuroglycopenic symptoms of hypoglycemia have no relationship to the adrenal ones (nervousness, anger, anxiety, manic/hyperactive/rambling, internal "shakiness" and sweating). The neuro symptoms are specifically from glucose deficit, and will not occur in relative hypoglycemia with absolute euglycemia. This is the lower responsiveness to environment, fading in and out of consciousness, or passing out... and it only occurs when sugar is very low, like, <50.

    The adrenergic symptoms of hypoglycemia are the ones we usually think of when we talk about being hypoglycemic, and that's the list above. Feeling like crap.

    Adrenergic symptoms have less of a relationship to absolute glucose level and are triggered mainly by 1) having an in tact nervous system (ironically, diabetics RARELY have adrenergic hypoglycemic symptoms because their nervous system is fried from hyperglycemia) and 2) your glucose dropping suddenly from insulin injection or secretion.

    As a nurse I can tell you most long term diabetics do not experience adrenergic symptoms of low sugar. They sit there out of sorts and sleepy, they look a bit pale (body can't have normal CV function without glucose) and their fingers are blue or white from it, they don't respond much although they do respond in simple words. Take their sugar and it's 35. They don't feel hungry, nervous, or shaky. The sugar drops without any counter regulation.

    Normal people do, and are far sensitive adrenal gland speaking to sudden sugar changes, because normal people do not have autonomic neuropathy.

    Ironically normal people are most sensitive to sugar instability weight gain - we are most likely to detect and respond and eat when our sugar goes from 120 to 80 very quickly. The ivory tower crew promotes the opposite idea.

  2. Also, when speaking of antisocial / criminals / violent individuals it is important to realize that alcohol abuse itself will cause various nutrient deficiencies and itself can cause glucose intolerance manifesting as hyperinsulinism and hypoglycemia. B-6 deficiency common result of alcoholism will cause glucose intolerance, magnifying the effect of insulin excess and hypoglycemia after alcohol .

    Did the hypoglycemia cause these problems, or does someone being an aggressive and violent person cause alcoholism, a lack of normal eating patterns, thus hypoglycemia?

    Speaking as a primary hypoglycemic without it being caused by anything other than my genetics / acquired damage to metabolism (as far as I can tell I am doing everything I can to have normal glucose tolerance and stable glucose levels, diet and supplement and lifestyle wise)... I can tell you that alcohol will 100% without fail cause me to have a hypo episode after I stop the drinking. Even if the alcohol has no carbs in it, a hour after drinking I'll become shaky sweaty and very hungry. Alcohol causes hypoglycemia, and it does this by preventing normal release of glucagon. This is why there is so much positive metabolic impact associated with "casual alcohol use"... alcohol is an effective hypoglycemic for people with IGT who are hyperglycemic. If you do not have much hyperglycemia, though, it will only cause hypoglycemia.

    Most people finish a night of drinking off with a carb binge, which is why club towns are littered with fast food joints open all hours. The reason is all people have a relative drop in sugar after drinking, so any night of partying is typically finished with a run to a doughnut shop or some mexican food.

    I tend to think alcohol's tendency to cause hypoglycemic reactions in people is the real reason so many kids become fat in college. It's well known kids go through a phase where they drink and party in college. Psychological theories aside, if you are now using a substance that is going to trigger unstable glucose, don't be surprised if you find your eating habits become crappier and you're spending a lot of nights pigging out on carbs after drinking.

    So when we see that violent criminals, who use alcohol because aggressive/anxious/agitated people tend to self medicate with alcohol (thus the reason manic people are often alcoholics, and many people with primary severe anxiety disorders too like my father - alcohol is the first benzo ever discovered), also have hypoglycemia, we need to separate whether or not that hypoglycemia is from the alcohol abuse itself *or* if it was even primary in the first place.

    Speaking personally yet again, I do not find I feel angry from low blood sugar. It modifies my personality in that I feel on edge and irritable but it does not make me more exhibited or aggressive.

    It is interesting, however, that low central serotonin levels could lead to larger magnitudes of insulin release, which makes a lot of sense and may explain a relationship between aggression and unstable glucose, if it exists.

    An acquaintance I know , who is otherwise weight gain resistant, is similar to myself in that she suffers from seasonal mood disorder (depression in fall/winter) and she also suffers from hypoglycemic reactions. Seasonal mood disorder is believed to be primarily a result of low serotonin in response to low light - and this could also explain a hypoglycemic tendency.

    For what its worth, when I take 5-htp I notice it triggers hypoglycemia for me... I tend to think that serotonin mediated increases in glucose metabolism , much like alcohol suppression of glucagon, can exacerbate low glucose in people who are prone to it. I also find that 5-htp will mess up fat burning and can cause symptoms of dopamine suppression if I take it in excess. It is worth noting that people on SSRIs tend to eventually gain weight and suffer mild effects of dopamine suppression (noted akathesia and higher prolactin, sexual dysfunction, weight gain).

  3. Just a correction, I said alcohol prevents glucagon release... it's more correct to say alcohol interrupts gluconeogenesis (but does not necessarily suppress glucagon, it just interrupts the effects of glucagon), and alcohol also seems to be insulinotropic as well.

  4. If you have ever seen end stage thiamine deficiency in a booze hound and what it does to a brain and behavior as well as glucose is a thing to behold. I have had that pleasure more times than I care to remember. Wernicke's encepholopathy and korsokoff syndrome are very instructive to the pathways covered in this series. Dr Kruse

  5. Woo 5htp and typtophan rely on insulin secretion to get into the gut......tryptophan has to compete for binding sites for trancytosis. This is protein meals don't increase typtophan levels in blood but a carb load will. It's why so many low carbbers get that flu they mention often. Dr. K

  6. Of course I have seen Wernikes many, many times - striking how the brain needs thiamin/glucose. I'll discuss the tryptophan shuttle, carbs, and protein in detail in the next several posts.

  7. Really enjoying this topic. Interesting that once again the definition of a medical condition is tied to a number instead of the patient's experiences. I personally experienced postprandial hypoglycemia for many years which mostly presented itself as extreme crankiness 90-120 mins after a meal (my boyfriend used a different, far more descriptive term) and an overwhelming desire to get to food. Any food. I was also very skinny at the time (interesting that of Itsthewoo2 brought up a point about healthy people being more sensitive to adrenergic manifestations of PRH).
    When my 8 year old daughter started having "sugar crashes" the morning after a pasta- or dessert-heavy dinner I knew it was real. Somehow the idea that it might have been psychosomatic never occurred to me. Funny that.
    By the way, Polovtsian dances is one of my favorite pieces.

  8. Duuuh I said b6 ... I meant thiamine (in my 2nd response). For some reason I always call thiamine vitamin B6.

    @Dr K - Yep, I was aware of the fact that insulin partitions amino acids so that it favors diffusion of tryptophan which is one reason high carb diets are noted to increase serotonin, and high protein diets will lower it. I do notice adverse mood effects when eating a high protein diet without carbs, but the effect is obliterated if I eat a lot of fat and not as much protein. Protein does funk up your mood. Fat, for me, helps my mood a LOT, in the context of a low carb diet. I try not to overdo the protein, and to fuel myself on fat and magnesium rich food as much as possible. I pretty much live on mixed nuts.

    I never could figure out why nuts made me feel SO GOOD. Other foods with similar macronutrient ratios did not. After eating nuts my mood was always better and my glucose tolerance was better (more stable; better fat burning signs, feeling energetic and just "balanced").
    When I started magnesium supplements, I realized the missing link - the nuts rock me because they are high in magnesium.

    The mood elevation from taking magnesium citrate is pretty much as close to instant as one can get, apart from shooting heroin.

    Tangents... anyway,... yes I was aware of the insulin leading to more tryptophan being converted to serotonin thing, however what I seem to experience is that taking 5-htp specifically seems to trigger insulin release or a glucose drop in of itself. This seems to suggest that a high dose of tryptophan (or 5-htp, a step further along) can somehow alter glucose metabolism either by raising insulin or using up blood sugar faster. I suspect that the influx of 5-htp, converted to serotonin/melatonin, may lead to a shift to glucose metabolism which can tehn cause a drop in blood sugar. Just a hunch I haven't verified either way.

  9. @Anastasia - I used to get PRH too, typically in the morning following breakfast (oats - aren't they low GI and therefore BGL-stabilising??). I would desperately need food due to extreme dizziness and tunnel vision. If I had coffee, I would crash a lot faster. I would also get a similar reaction if I had been cycling (fully carbed up, of course), drinking carbs on the bike, and then stopping for coffee and a bran muffin at our usual coffee stop. Within 30 minutes (typically as I was about to ride the last 10km home), the wheels would come off my BGL's... not a nice feeling whilst trying to stay upright on the bike and negotiate traffic. At its worst, it was all I could do to get home, and eat multiple slices of toast and jam. Sometimes I would need to sleep for a few hours after.

    But even within this scenario, there are just so many confounders outside of the carbohydrate dose. Was it the training? The caffeine? The carbs? The gluten? The dairy with the oats? Was I deficient in something?

    All I know now is that being fat-adapted, changing my training style, being gluten-free, being dairy-free, etc, has fixed it. My theory of everything is that everything needs to be rebalanced, not just single macro/micronutrients.

  10. @Jamie: "fully carbed up" used to be my catch-cry. Of course, getting carbed up in the morning before a ride pretty much guarantees you have to keep snacking on crackers, muesli bars, muffins (low fat of course), bananas, followed by a nice bowl of pasta at home. Now we go out on a coffee. Riding past as the bunch is having a recovery muffin at Michel's patisserie is priceless.
    Sorry Emily I didn't mean to highjack the topic. I think being active makes you more vulnerable to blood sugar fluctuations. Many weekend warriors believe it gives them a perfect excuse to load up on sugar to "improve their performance". But i think its much nicer to be a content Sunday morning rookie cyclist than a buzzed up and irritable wannabe.
    Thanks, Anastasia

  11. With my sports nutritionist hat on, you always had to tell people that as soon as they reach for the lolly water (and even more so for the gels), you had to stay on schedule (normally every 15-20 minutes) for drinking or your energy levels would drop out - rapidly. You would generally try to get people to use a protein/carb drink as it kept them on a more even keel (the day I swtich over to a PRO/CHO formula, I couln't believe how much of a rollercoaster the CHO formula used to have me on). And you would advise to save the gels until late in a race/or in an emergency to get you home... once you started on those, you just had to stick with them. And you would generally feel pretty rough in the gut after.

    So glad those days are long gone. Now a coffee ride is exactly that - a coffee ride. Not an Olympic-sized mocha latte with a slice of cake (because riding 60km means you have earned it), like most of the MAMIL's enjoy.

  12. Thank you for putting it all together! Fascinating series. I'm very much looking forward to more of your thoughts on PCOS. From speaking with the ladies attending AHS, it seems that nearly everyone has it to some degree still, despite going paleo, or nearly paleo.

  13. @Katya

    Paleo will not help someone with PCOS.
    Low carb, however, will.
    If the paleo diet is too high in fruits and starchy tubers, and if she is not taking supplements specifically to maximize her glucose tolerance, she will find her PCOS is poorly controlled.

    If I eat absolutely non-paleo food, which is high fat, low carb, and my diet is loaded with glucose tolerance enhancing nutrients, my PCOS is in total remission.

    If I eat a lot of fruit and potatoes, I can expect a blip of acne.

    In a way I don't like this "paleo" trend. It imbues certain foods with magical powers, when in reality there is a clear scientific explanation - people feel better on paleo , usually because they are greatly reducing dietary glucose, decreasing dietary allergens, and also increasing nutrients.

    Calling an intervention "paleo" prevents you from understand why one is really benefiting.

    In the case of women with PCOS, she would thrive on a diet - paleo or not - with very low carb, with glucose tolerance enhancing supplementation. If she just tries to "paleo" but avoids chromium/inositol supplements because they are not paleo, and eats a lot of potatoes and fruit, she's not going to do well with her PCOS.

    This romantic notion of a paleo diet actually hurts people with diseases . It's fun to think of yourself as eating the real human diet or whatever, but ultimately your condition isn't going to improve unless you are taking steps to improve it, and that means understanding why what you are doing works.

  14. Hi,

    I have read studies saying that no one who says they are hypoglycemic actually are when tests are done during a fast.

    In fact I think it's the increased catecholamine release during the fasting that drives the wiredness/euphoria and possibly anxiety, based on the individual. AND I also think it masks the symptoms of the perceived "hypoglycemia".


    /Jens (Sweden)

  15. The hypoglycemia occurs 90-120 minutes after a pure carb load, not after a fast. The data as such is in the post. Fasting is a different situation.

  16. I have reactive hypoglycemia. I took an OGTT and after one hour my blood sugar dropped. I've had 35 in the glucometer and scary episodes like blood sugar crashes after eating an apple. In this scenario what can you suggest to overcome this? If it is enterely possible? I'm 20 years old, female. I already given up wheat and gluten, and it's been really hard fighting my family and friend's beliefs. I seek help from a well known doctor in my country and she recommended eating carbs every 2 hours. It almost killed me. Since then I've been reading many blogs and papers, and I have to say yours is one of my favourites. Thank you for everything.

  17. Hi.Here in India,the ones who get the psychosis due to hypoglycemia are misunderstood to have been possessed by ghosts.Till now even I believed it but not further...


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