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Once upon a time, sucrose was the main ingredient in the diet of lab rats, but now starch is used.  The government thought it knew what type of nutrition rats needed, so it recommended purified diets for the sake of science.  Then, the rats started getting diseases, so they started tweaking the purified diets.  Sound familiar?

Here's a little snippet from history, from this source:


Carefully defined purified diets with known amounts of nutrients, vitamins, and minerals have been recommended for use in animal studies of toxicity and carcinogenicity.  The National Research Council Committee on Laboratory Animal Diet has emphasized the need to use such defined diets in order to make valid comparisons of studies in different laboratories (Newberne et al., 1978).  For this reason, the American Institute of Nutrition (AIN) Committee on Standards for Nutritional Studies has recommended a purified diet composed of commercially refined proteins (casein), carbohydrates (sucrose, cornstarch), fat (corn oil), and fiber (cellulose) with added mineral and vitamin mixtures and supplemental choline and methionine (AIN-76A Purified diet) (Bieri et al., 1977; Bieri, 1980).

Since the introduction of this diet there have been reports of excessive bleeding (Roebuck et al., 1979; Medinsky et al., 1982), nephrocalcinosis (Nguyen and Woodard, 1980; Medinsky et al., 1982), and fatty liver (Medinsky et al., 1982; Hamm et al., 1982) in rats fed the AIN-76A diets.  Excessive bleeding has been prevented by increasing the level of vitamin K added to the diet (Bieri, 1980).  Problems with the development of fatty liver appear to be related to the high concentration of sucrose used in the diet (Hamm et al., 1982), and make the use of such a diet questionable in animal studies that require normal hepatic morphology and/or function.  The current study was designed to determine more precisely the role of dietary sucrose concentration in the ddevelopment of hepatic triglyceride accumulation.

The AIN updated the diet in 1993, known as the AIN-93 diet.  (“AIN-93” may be followed by “G” or “M” to designate growth or maintenance.)  The AIN-93 diet, currently used, recommends corn starch, but includes some glucose and dextrinized corn starch (broken down to 4-unit carbohydrates) in order to aid in pelleting and to reduce the amount of time and heat needed for pelleting.  Soybean oil replaced the corn oil in order to balance omega-3 and omega-6 fatty acids.  Just in case they might be essential or beneficial, they added chromium, fluoride, boron, vanadium, arsenic, nickel, lithium, and tin.  The official report gives the following reason:


Many of the ultratrace elements are found in plentiful quantities in the natural ingredients that make up cereal-based diets, but their concentrations in purified diets are often very low, and in chemically defined diets, they may be completely absent.  Purified diets without added ultratrace elements suport growth and reproduction, but investigators have noted that animals exposed to stress, toxins, carcinogens or diet imbalances display more negative effects when fed purified diets than when fed cereal-based diets (Bounous 1987, Boyd 1972 and 1983, Evers 1982, Gans 1982, Hafez and Kratzer 1976, Longnecker 1981).  This suggests that detrimental effects may occur with the omission of some substances found in the more natural, cereal-based diets; some of these substances may be the ultratrace elements.

The amount of vitamin K was increased by 50% (this was after a previous10-fold increase between the AIN-73 diet and the AIN-73A diet), and the form was changed from the toxic, synthetic vitamin K precursor menadione to the natural, plant-based form of vitamin K, phylloquinone.  The ratio of calcium to phosphorus was also increased.  This made the diet much less likely to cause kidney calcification in females:


Experiments showed that female rats fed the AIN-93G diet for 12 wk exhibited no increase in kidney calcium when compared with those fed a cereal-based diet.  On the other hand, rats fed the AIN-76A diet had 23 times more calcium in their kidneys than rats fed the cereal-based diet.  Calcium concentration in the kidneys of male rats was not affected by either diet.

The concentration of vitamin B12 was increased because the AIN-76A diet failed to minimize methylmalonic acid, a marker of B12 deficiency.  The concentration of vitamin E was increased 50% because the amount of fat had been increased from 5% to 7% and because soybean oil contains more omega-3 than corn oil, and omega-3 fats are more vulnerable to oxidation than omega-6 fats.  The amount of choline was increased from 0.08% to 0.1%.

Are all these changes sufficient?  The increase in choline obviously isn't, since animals fed three times the recommended amount during pregnancy give birth to rats with a 30% increase in visuo-spatial and auditory memory, grow old without becoming senile, are less vulnerable to neurotoxins, are better able to multi-task, and have a lower rate of “interference memory,” which is what makes you forget where you parked your car when you get done grocery shopping.  I describe this research in my article “Vitamins for Fetal Development: Conception to Birth.”

Another reason the choline level is clearly inadequate is because lab animals fed high-sucrose and high-fat diets develop fatty liver disease.  But more on this in my next post.  Should be up tonight or tomorrow.

Like the original report for the AIN93 diets stated, the content of purified diets containing what we believe to be essential depends on current knowledge, which is always subject to change:

It is unrealistic, however, to presume that a perfect diet can be formulated, one that can satisfy all circumstances.  Moreover, the ingredients that supply the nutrients and the concentrations of individual nutrients themselves are based upon current knowledge in the field and may change with time.  This may result in a need to change a standard diet formulation.

Before the advent of controlled experiments, purified lab rat diets, the refining and fortification of foods for human consumption, and the food pyramid, both rats and humans ate natural foods, and ate instinctively, “listening to their bodies.”  When eating became science-based, humans and lab animals started developing degenerative disease as the norm rather than the exception.  The primary culprit?  Human arrogance.  It primes us to believe that we almost know everything there is to know.  If we just do a few more studies.  It's the type of arrogance that leads us to perform epidemiological studies and then believe that the results “have been adjusted” as if we know what all, or most, of the confounding variables are.

Feel like a lab rat yet?

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  1. That sort of thinking… well, I thought so too, once upon a time. Back in grad school, I thought we understood all this stuff about nutrition and endocrinology and metabolism… I thought hand-waving about "things we haven't discovered yet" was a weak argument and mostly nonsense.

    Twenty years later… I go to read up on my diseases and they're talking about micronutrients and hormones that DIDN'T EXIST when I was in grad school!

    I will simply NEVER believe we have "gotten it" after that.

    For me, it's the most compelling evidence in support of whole foods – and the "stuff we haven't discovered" is a HUGE unknown.

    By definition, we never know what we don't know…

  2. From the material, the issue appears to be a lack of knowledge about the exact nutritional requirements of the rats. This information was only made clear when a purified diet was fed. Although the heath costs to the animals are deplorable, the information provided also allows us to better understand the interaction of the different dietary components.

    Essentially, because of the huge micro- and macro-nutrient variance in natural ingredient diets (growing location, soil quality, yield quality), an ideal diet would be a purified diet, if all the requirements were known with certainty.

  3. Chris – I think your clarity is great actually. I was referring to the dearth of my knowledge of biochemistry. (I'm taking a course in it next semester though so hopefully it will make more sense to me then…)

    But your commentary does help put all the science into context, something that I feel a lot of research studies fail to do. What's the point of doing all the research if the theory isn't translated into practice?


  4. Laura,

    Nice to meet you too, thanks! If I'm unclear on anything just let me know. I do deal with advanced material but I try to make it understandable.


    I don't think anyone is looking at the interaction between fructose and PUFA, but if you put the data together from a couple studies, you will see that fructose and relative choline deficiency are necessary for steatosis and PUFA (or perhaps specifically n-6?) is necessary for the progression from steatosis to steatohepatitis. I'll explain this much better in a coming blog post.

    Sesame is also pretty high in phytoestrogens but I'm not sure how much makes it into the oil. Either way, I think a teaspoon is pretty moderate and I wouldn't worry about it if it really makes you happy. Hapiness is underrated.


  5. But Chris —

    You make no mention of the studies that compared the earlier diets to the first of the refined diets. Without these studies, the scientists would have had no reason to think that the new, standardized diets gave results comparable to the body of then-existing science.

    Therefore, we could deduce the existence of a substantial scientific literature on this topic. That is, we could if the literature on rat nutritional studies qualifies as remotely competent science.

    I gather that it fails this test.

    The discovery of the need to add nutrients to standard purified diets is damning. It should have been discovered long before anyone would consider relying on the diets as standards.

  6. Chris,

    Another question, even less related, but I would really appreciate it if you could share your opinion.

    As you may remember from my previous comments, I am a big fan of Asian food. I do my best to adapt Asian cuisine to eliminate problematic ingredients.

    One thing I'm stuck on is sesame oil; sesame oil is a semi-essential flavoring in Chinese food, and it is also extremely high in O-6. In addition it is used "toasted," which I fear may be a code-word for oxidized.

    I haven't been using it because I generally shun all vegetable and seed oils.

    What's your take on toasted sesame oil? How much would a teaspoon of sesame oil hurt me?

  7. Chris,

    Something has been on my mind and I figure you are the right person to ask. Are you aware of any human studies on the effects of fructose in the context of a low PUFA diet? Has anyone ever done a study like that?

    If I were a nutritional scientist, that's the first thing I would study. Perhaps that is something you could look in to?

  8. Nice meeting you this weekend Chris. I'm looking forward to following your blog after hearing you speak (and our interesting dinner conversations of course). I think your explanations make a lot of sense of the mixed research findings out there.
    Hopefully I'll be able to understand the majority of your posts!
    -Laura Schoenfeld

  9. Yes indeed O Primitivo, the paradigm of Nutritionism rather than Nutrition.

    Thus rat diet experiments are conducted with variations of Industrial Foods rather than variations of McCarrison's Real Foods.
    Come to think of it, it's the same thing with Human studies – so called Mediterranean Diets with omega 6 oils by Unilever instead of Olive Oil -NUTRITIONISM

  10. Great post! Reminds me of Pascal in Pensees when he says: "The mind of this supreme judge of the world is not so independent as to be impervious to whatever din may be going on near by. It does not take a cannon's roar to arrest his thoughts; the noise of a weathercock or a pulley will do. Do not be surprised if his reasoning is not too sound at the moment, there is a fly buzzing around his ears; that is enough to render him incapable of giving good advice. If you want him to be able to find the truth, drive away the creature that is paralyzing his reason and disturbing the mighty intelligence that rules over cities and kingdoms.

    What an absurd god he is! Most ridiculous hero!"

    I always think of that when I'm reading nutrition research :/

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