Sunday, May 20, 2012

Do Sugar and/or Saturated Fat Make You Stupid?

Two more heavily publicized papers came out in the past week or so, just in time to be fodder for questions at my talk on Evolutionary Psychiatry and Alzheimer's Dementia in the upcoming week.

Have you ever heard the Adagio from Spartacus? Hang in there for a little bit. Around 1:09 you get the early rendition of one of the more romantic themes in classical music, repeated with greater power later in the ballet (2:47 and 7:04). The Russian composers really knew how to sock it to you with a good theme.

Can we say the same of rat researchers from UCLA?  Well, excepting our own good friend and AHS president Aaron Blaisdell, the jury is still out… These researchers pulled out some interesting things, though, in their little study on 24 rats.

"'Metabolic syndrome' in the brain: deficiency in omega-3 fatty acid exacerbates dysfunctions in insulin receptor signaling and cognition."

This paper combines everything awesome and evil all at once.  Rat study.  Fructose!  DHA.  Mazes.  The authors even begin the paper not with an abstract but with highlighted Key Points:  We provide novel evidence for the effects of metabolic dysfunctions on brain function using the rat model of metabolic syndrome induced by high fructose intake.  Etc.

So… we have some rats.  There are two diets and two drinks.  Group 1 gets regular rat chow with omega 3 and water to drink.  Group 2 gets regular rat chow with omega 3 and a 15% fructose drink instead of water.  Group 3 gets water and omega 3 deficient diets (and I doubt it is so easy to make a human in the wild quite so omega3 deficient as these rats), and group 4 gets the double whammy of an omega 3 deficient diet and the 15% fructose solution.  The diets go for 6 weeks, and in that time, we have a pretty remarkable change in the fructose-slurping rates.

The fructosed rats drink a lot more than the plain water-drinking rats, and even though they eat less food than the plain water rats, they take in more calories.  By the end of the 6 weeks, the fructosed rats have high glucose and insulin levels, and the triglyceride levels of poor group 4 (given fructose and omega 3 deficient diet) are over twice the levels of group 1 (omega 3 food + water).  The researchers found that the omega 3 in the diet seemed to protect the group 2 rats a little from the fructose, with less weight gain and less rat metabolic syndrome.

These rats had also been trained to go through a maze, and the fructose-poisoned omega 3 depleted rats did worse than any of the other groups in remembering how to get through the maze.  They lost the maze race, big time.  Again, the rats who had fructose and omega 3 had relatively preserved maze-solving abilities.

The researchers measured very specific elements in the rats' bodies and brains after the experiment.  Measures of energy metabolism were decreased in poor group 4, whereas omega 3 seemed to increase energy metabolism.  Other chemicals known to be important in the ability of the nerves to adapt and change according to different stimuli (called synaptic plasticity) were very decreased in the omega 3 deficient rats, and very much decreased in the fructose-poisoned omega 3 deficient rats.  Group 2 rats (+ omega 3, + fructose) had, again, some protection from the bad effects of the fructose.

And, not surprisingly, the omega 3 deficient rats had a decreased amount of DHA in the brain and an increased amount of omega 6 fats and their metabolites, like arachidonic acid.

Fructose in excess is well known to cause metabolic syndrome (hypertension, hypertriglyceridemia, and hyperinsulinemia are typical symptoms).  Did you know that metabolic syndrome affects the brain as well?  Of course you do. There are plenty of rat studies showing that downing vast quantities of coca-cola fructose is a pretty lousy idea, if one cares about one's liver or brain.  (I recommend this segment of the HBO Weight of the Nation series about the liver, and a good bit halfway through the next segment about sugar-sweetened drinks.)

So, we've now proven that fructose is bad (in the context of an excess calorie diet), and omega 3 is protective, and the main point is to not deprive your rats of omega 3.

Sugar can indeed make you dumb (in the context of an excess calorie diet).  Eating lab rat chow completely devoid of omega 3 can make you even dumber.  I don't recommend it.  But you can see how a modern processed food diet can mimic these changes.  Soda or juice or red bull or sweetened beverage of your choice and a lack of omega 3 does not a happy liver or brain make, and the changes occur quickly.

And now the second diet and dementia study of the week (involving actual humans! However, it is another observational study from the hospital where I'm academically attached).  Participants in the Women's Health Study (about 39,000 female health care professionals) filled out a food frequency questionnaire at baseline, and beginning five years later, an older sub cohort (about 6000 women over 65) underwent serial cognitive testing via telephone over the course of an additional four years. Data was gathered and statisticians went to work.

The women underwent cognitive testing three times, with the time between the 1st and 3rd test being an average of 4 years.  Women tended to do better the second time than the first time (having learned what the tests were going to be), but at the end of the four years, the scores dropped for most women from the second to the third test.  It declined the most for women who ate the most saturated fat, and actually test scores continued to improve for women who consumed the most monounsaturated fat.

There were no associations between total fat, trans fat, and polyunsaturated fat (which is mostly omega 6) and cognitive change.

By the time you pull out covarites you have a mell of a hess.  Saturated fat intake was associated with lower rates of high cholesterol, by the way (statinization??  This part of the study occurred from 1998-2002.  Statins came out in the late 80s and lipitor, the biggest-selling one I believe, was released in 1998. Though it is hard to tell if women on statins would have automatically been put into the "hypercholesterolemia" group or if just total cholesterol was used to make this group.  There are many frustrating things about the way the data is presented in this study).  MUFA (olive oil) consumption was also correlated with lower total cholesterol.  Women with known cardiovascular disease (history of a myocardial infarction, stroke, coronary artery bypass or stenting) were taken out of the data and the trend remained similar.  More total fat intake was associated with lower exercise, smoking, and higher BMI.  Previous epidemiology studies all linked saturated fat intake to poorer cognitive function over time.  The main difference in this study is that these health care professionals had much lower total trans fat intakes than the average American.  Trans fats have been previously associated with poorer cognitive function in other epidemiological studies, and trans fat consumption tracks with saturated fat consumption.

The paper is a little too brief and too heavy on statistical mumbo-jumbo to bother much with coming up with any mechanisms.  It does recommend a Mediterranean diet at the end, and immediately classifies PUFAs and MUFAs as "good fats" and saturated fats and trans fats as "bad fats" in the discussion.

I think when it comes down to it, we will find that these women who were chowing down on the saturated fats in the 1990s are going to be women who were less likely to take care of their health in other ways.  The olive oil fans were also more educated (even then olive oil was starting to be popular) and likely to take the best care of themselves.  I'm not surprised to see these correlations.  I still can't figure out how saturated fat all on its own can cause cognitive decline, mechanistically.  I find it very interesting that the highest saturated fat eaters had lower levels of hypercholesterolemia in this large group, and the paper makes no attempt whatsoever to explain this finding.  Hmmmm.


  1. I finished a 30 day raw juice fast a few weeks ago. It was really rather easy, believe it or not. Except it got difficult whenever I drank a lot of fruit juice. Veggie juice (kale, parsley, celery, carrots, etc.) didn't taste very good, but it did not make me hungry. But, boy!!, I could barely get past the fruit juice (apples, tangelos, melons, etc.) About an hour after drinking the tasty and refreshing fruit juice, I would become so hungry!

    Early man did not have big, fat, juicy, sweet fruit. Such did not exist until we developed them out of wild fruit, within the past 10,000 years or less.

    I have also noticed that (perhaps) paleo dieters whose ancestors come from the tropics are more likely to rave about doing paleo with fruit and fruit juice, but those whose ancestors come from places far away from the tropics are more likely to rave about the virtues of doing paleo with veggies and veggie juices. Just a thought, perhaps I am connecting the dots incorrectly.

    On Netflix one can get lots of documentaries about various primitive tribes. It is very eye opening to see Inuit type people in north eastern Siberia eat mostly whale and seal products, including massive amounts of blubber, yet they have zero heart disease. And they eat very little else, perhaps some odd veggies, but zero fruits. On the other hand, there are primitive people near the tropics who eat fruit regularly, and they have no heart disease.

    1. And yet, some Paleo types will not believe that eating local and seasonal means anything- when it is everything.

  2. Big elephant in the room that epidemiologists, bless their widdle hearts, can't really control for: illicit drug use. So your contention that it probably has to do with health-consciousness is valid. There are likely other factors not controlled for too.

    I am extremely skeptical of their ability to accurately predict how much trans fat and omega-6 they consumed because of all of the different processed foods containing them. It is impossible, don't try to argue, how are you supposed to be accurate about those when there are 3278472347248234328 processed food-like thingies in boxes all with different composition of industrial fats?

    In the event that it actually way saturated fat, would that mean that saturated fat -necessarily- produces cognitive impairment? I decided to research lipotoxicity a while back and I figured out that palmitic acid is "lipotoxic" but only if the metabolic machinery isn't working well. Leptin resistance, insulin resistance, downregulated this and that protein with a long name, insufficient nutrients, etc. So until I see a controlled trial on very healthy people eating a nutritious diet, exercising, sleeping, etc, I'm not going to believe anything about saturated fat...

    ...or sugar for that matter. Rat studies are all right, and show us many things. Including that a high fat diet doesn't necessarily produce metabolic syndrome if you give it DHA from the start when it is most effective as a preventative agent. And what of the dozens of other interventions you could make to allow nutrients to be metabolized more healthfully? Alas, rat studies rarely do this. Rats are confined and fed diets of processed junk and vitamin powder, not really comparable to humans. You can find plenty of studies say that X thing is unhealthy, except when you add in some nutrients and then BAM Mr. Rat is a rockstar.

    I look to the Japanese to take some of their healthy people, feed them a good diet with plenty of all of the nutrients and even some of the non-essential but beneficial, and then substitute butter for olive oil, measure the difference. Boom, we have science. Stab it!

    Until then, Fuuuuuuuuuuuuuuuuuuuuuuuuu nutrition researchers. Hands of my food, it's mine!

    1. I did mean to add that a group of >71 y/o female health professionals will likely have a lower than average incidence of illicit drug use, and etoh use was accouned for.

    2. True. I wonder if the effects in early life would carry over, though. The same people who used them in the 60s might be the ones who ate more saturated fats later.

      That is just one prospect out of many. It is also plausible that the most stressed people would eat the most saturated fat as a comfort food.

    3. Just wondering if they identified the sources of saturated fat? I'm picturing the group of nurses that send one out to get burgers and shakes for lunch, then sit down to a pile of fettucine alfredo or chili cheese dogs for dinner.

  3. Yeah, I just don't see the lipotoxicity from dietary animal foods.

  4. Time to consider gut microflora in its relation to dietary fats, lipids in the brain, and ultimately its function (see the eye-opening new study by Wall et al. Am J Clin Nutr "Contrasting effects of Bifidobacterium breve NCIMB 702258 and Bifidobacterium breve DPC 6330 on the composition of murine brain fatty acids and gut microbiota.")
    As we suggested in our 2003/2005 Medical Hypotheses papers (lactic acid bacteria fatigue/probiotics and depression), the tail may be wagging the dog.

    Brilliant blog, keep up the critical thinking...

    Alan Logan

    1. Very interesting! Pulled the new paper and looking up the Med Hypo ones… thanks!

    2. Dr Deans

      Not to inundate you with yet more reading but it may be worthwhile to have a look at the In Press work of Cani, et al
      "Involvement of gut microbiota in the development of low-grade inflammation and type 2 diabetes associated with obesity" in Gut Microbes journal

      and also from the Evolutionary perspective

      Wong, et al. "Gut microbiota, diet, and heart disease" J AOAC Int 2012;95:24-30

  5. I really wish I could be at your talk on Evolutionary Psychiatry and Alzheimer's Disease. Is there any chance that you will post something here afterwards?

    1. I don't think it will be recorded. I may do a variation of this talk at AHS.

  6. Rock Star mice on a high-fat diet:

    it turns out, all they needed was intermittent fasting; then they "outperformed" the "healthy eating", all-day grazing rats.

    Palmitate may be associated with cognitive impairment because it is the main endogenous SFA, produced from excess carbohydrate. Most dietary fats supply proportionately less palmitate than lipogenic metabolism will. Easpecially on low-carb diets:

    1. right - and I still haven't seen anything convincing about lipotoxicity without hyperglycemia i.e. excess energy states in general, which is obviously way more complicated than saturated fat. And yes, from de novo lipogenesis you get palmitate, for sure. Nice find on the IFing rats.

    2. This quote from the IF story puts lipotoxicity plus hyperglycaemia in context.
      It's not what we're eating, it's when we're eating it? It looks as if even fructose will be tolerated in an IF setting, which explain hunter-gatherers who are healthy while regularly binging on honey.

      "The Salk study found the body stores fat while eating and starts to burn fat and breakdown cholesterol into beneficial bile acids only after a few hours of fasting. When eating frequently, the body continues to make and store fat, ballooning fat cells and liver cells, which can result in liver damage. Under such conditions the liver also continues to make glucose, which raises blood sugar levels. Time-restricted feeding, on the other hand, reduces production of free fat, glucose and cholesterol and makes better use of them. It cuts down fat storage and turns on fat burning mechanisms when the animals undergo daily fasting, thereby keeping the liver cells healthy and reducing overall body fat.

      The daily feeding-fasting cycle activates liver enzymes that breakdown cholesterol into bile acids, spurring the metabolism of brown fat - a type of "good fat" in our body that converts extra calories to heat. Thus the body literally burns fat during fasting. The liver also shuts down glucose production for several hours, which helps lower blood glucose. The extra glucose that would have ended up in the blood - high blood sugar is a hallmark of diabetes - is instead used to build molecules that repair damaged cells and make new DNA. This helps prevent chronic inflammation, which has been implicated in the development of a number of diseases, including heart disease, cancer, stroke and Alzheimer's. Under the time-restricted feeding schedule studied by Panda's lab, such low-grade inflammation was also reduced."

  7. Maybe I'm being too cynical here, but are the designers of the saturated fat study even interested in finding the truth? Maybe it's just based on the opinions I've been exposed to, but food frequency questionnaires seem like a tool to find what you want to find rather than to find anything that's actually happening. We always hear about how the studies we want can't be funded, but then money is spent on carrying out these pointless studies?

    1. These researchers almost *always* find that healthy, wealthy, educated, non-smoking, exercising olive oil, fish, and berry eaters are healthy, wealthy, educated, non-smoking, exercising olive oil, fish, and berry eaters. And these *massive* studies are funded by the NIH, not even by the Berry Association of America (1) or the Olive Oil Foundation (2).

      The only epidemiology I find truly interesting are the studies that don't quite fit. The smoking, non-exercising massive coffee drinkers who live longer and have less depressive disorders. Now that is an interesting finding, particularly in the light of how coffee seems to cause insulin resistance and is often consumed with fake creamer and sugar. That kind of finding is few and far between.

      (1) and (2) just made those up

  8. '..I still can't figure out how saturated fat all on its own can cause cognitive decline..'

    Saturated fatty acids promote iron absorption and inhibit manganese absorption

    They also inhibit copper absorption


  9. They normally use simple salts of minerals in these studies, which may not be how they are absorbed from food.
    (could apply more to mineral water, sea salt, perhaps)
    Minerals which form soaps - like magnesium - could be bound up (as magnesium stearate, for example) but does this apply to magnesium from, say, chlorophyll?

  10. Hi George, I know what you mean, but it seems the same thing does happen with food. For instance, Klevay found that heart disease in mice caused by a diet high in saturated fat could be prevented by extra copper.

    Copper is absorbed through a transporter called Ctr-1, which very interestingly, can be down regulated by dietary fructose. The copper people think this is why fructose is bad for you: it makes marginal copper deficiency, which apparently most of us have, worse.

    Have you seen this interview with Ron Krauss, who has found that saturated fat makes red meat toxic, and thinks it might be because it promotes iron absorption? It's right at the end of the interview.

    1. interestingly that recent red meat will kill you study looked for the iron link and didn't find it. I forget exactly how they looked for it, but they were surprised...

    2. And the red meat as killer link, such as it is, isn't matched by any SFA link.
      In fact, SFA seemed to ameliorate the red meat associations; if there was a harm from the meat, SFA protected against it.
      And there are no positive associations between SFA and the diseases that were cited as major causes of death in the meat study.

      If a seismologist discovered an increased risk of an earthquake as big as the increased risk associated with red meat - say a 20% higher chance of the big one hitting on Xmas day, compared to any other day - would anyone think that this was worth broadcasting, even in a shaky city like SF, even if it was known to be accurate?

  11. Shouldn't it read, 'Does sugar and/or sat. fat make you stupid?'

    1. I don't know the accepted for and/or… someone call Strunk and White!

    2. Seems 'do' works for the and, while 'does' works for the or. Must be all the sugar and saturated fat making my head spin =P

  12. Regarding the rats and sugar study, it is important to recognize the amount of fructose consumed in ratio to an average human intake. I completely agree with this quote:

    "It can be calculated from study data that rats consumed 7 grams of fructose per day, which is comparable to an adult human consuming 1028 grams. A consumer would have to eat 66 apples or drink 51 cans of soda per day to reach that level. Clearly this is a highly exaggerated and distorted version of the typical human diet."

    It comes from a pro corn industry site, but they do have a massive point.

    Regarding Roger Bird's quote, "Early man did not have big, fat, juicy, sweet fruit. Such did not exist until we developed them out of wild fruit, within the past 10,000 years or less." Are you serious? We had an abundance of sweet tropical fruits which were most likely gorged upon by humans. Denise Minger wrote a good post on this a while back.

    1. Yes, according to Staffan Lindeberg's Food and Western Disease, ancient fruit isn't really less sweet than current fruit, just smaller.

  13. I am reminded of the initial PaNu posts in which Dr. Harris proposed that it (Paleo) was about what not to eat...

    In the broader sense "not to eat" included "Intermittent Fasting" ("IF"). Thus "not eating" is a part of the Paleo approach. We can speculate why this might be so, and it is easy enough to imagine that without refrigeration, without easy food storage, and in a hostile environment, meals might be less frequent or some very small and others very large. And some loaded with bacteria... Or nothing but fructose from fruit.

    In our lives it seems that the idea of regular meals, each just a few hours apart, seems to not work very well, because the body never shifts is its energy requirements away from the readily available recently consumed nutrition. In short, the systems are constantly digesting food and providing sustenance on that basis. Apparently the body was designed not just to deal with hunger, but it is a necessary condition for health.

    Maybe that is in part why diabetics do better on a weight loss program? It's not just the weight loss, but the body being forced to look for other stores of energy?

    It's just a thought...


  14. Could it be the way it was cooked? The meat and saturated fat in itself is not bad, but it is they way it was cooked. If it was barbacued or grill over charcoal with black marks on the meat and fat, then the proteins have become glycoslated producing Advanced glycation end-product (AGEs) which may not be good for the brain.

    If the meat was cooked using polyunsaturated vegetable oil, then the oxidized rancid oil would cause inflammation and damage to arteries and blood vessels -- also not good for the brain.

    Perhaps the fat study will picked up the association that those who ate a lot of saturated fat cooked it in unhealthy ways that produces AGEs and inflammation that is harmful to the brain.

    What do you think?

  15. Here's another interpretation; diet was self-reported.
    I predict that people who lie to minimize reporting of "unhealthy" foods are more competitive than people who report consumption honestly or exaggerate.
    In fact, in popular culture, people who exaggerate intake of "unhealthy" foods are often proud of their ignorance or seek to make a virtue of it.
    So reporting of "unhealthy" food intake is itself a sensitive marker of ambition and self-perceived intelligence, or even of how society has judged one's intellect in the past.
    And these - ambition and confidence, as well as cognitive ability - are the qualities that are required to do well in intelligence tests.

  16. Hi Emily --

    One of my interests is chronic pain. And I suspect that chronic pain - as a condition in and of itself - will ultimately be seen as another one of those metabolic-syndrome related conditions.

    But I can't find much research specifically about diet and pain.

    Do you know of any?


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