Is Butter High in AGEs?

A butter-loving reader posed the following question to me:

Thanks for all the work you do. Any chance you could post something on the AGE content of butter? Does it make a difference if AGEs are endogenously or exogenously produced? Thank in advance.

Suffice it to say he liked my answer.  I'll repeat it here, with a little more detail.

The reader may have seen Dr. William Davis's recent post, “The Anti-AGEing Diet,” in which he wrote the following:

And minimize or avoid butter use, if we are to believe the data that suggest that it contains the highest exogenous AGE content of any known food.

Are we to believe this data?  I don't.

Don't get me wrong.  I love Dr. Davis's blog.  I'm just not feelin' the idea of measuring AGE contents with immunoassays instead of mass spectrometry.  Sorry for the big words.  I'll explain in a second.

Advanced glycation end products, or AGEs, are rogue chemical reaction products that result from the interactions between sugars or oxidized polyunsaturated fatty acids (PUFAs) and proteins.  The AGEs can then damage proteins, DNA, and possibly phospholipids, and thereby wreak havoc on our cells.

Dr. Davis links back to a previous post he made on butter, “Butter: Just because it's low-carb doesn't mean it's good.”  In that post he links to a 2004 analysis of the AGE content of 250 foods.  These authors recently produced a more extensive database of the AGE content of over 500 foods.  The results?  Butter, butter, butter, butter, butter.  The concentration of AGEs in butter was just massive.  In fact, they found that butter contains 5,000 times more AGE than whole milk!

Why don't I believe this?  For starters, it's not very realistic.   The specific AGE these authors were looking for is carboxymethyl-lysine.  CML is formed during the breakdown of glycated proteins — proteins that have been jumped and mugged by sugars such as glucose or, in the case of milk, lactose — or from the specific reaction of the amino acid lysine with a compound called glyoxal.  Glyoxal is formed from the spontaneous oxidation of glucose or as a byproduct of the oxidative destruction of PUFAs.  These processes are all accelerated by the presence of phosphate and trace metal ions in solution.

So where is all this CML coming from?  Milkfat is extremely low in PUFA to begin with.  Making butter from milk removes most of the protein and sugar and removes the majority of the phosphorus originally found in the milk.  On top of all of this, most of the water is removed, and removing water increases the stability of almost anything.

Is it possible for AGEs to form in butter?  Sure.  There's still lysine, and there's a little bit of PUFA, and there's still traces of carbohydrate.  But is it likely that butter has 5,000 times as much CML as whole milk?  Not very.  And someone who is going to claim this should have really good evidence to back it up.

So how good is the evidence?

The authors who composed these databases quantified CML with an immunoassay.  This means that they took an antibody that is supposedly specific for CML and quantified how much was in different foods by the relative amount of antibody-binding that occurred.  That's why you see the values reported in arbitrary “AGE units” instead of real units like “milligrams.”

There are a lot of problems with immunoassays.  Antibodies sometimes have spectacular specificitiy, but often have abysmal specificity.  We make a lot of antibodies in our intestines that are “polyreactive” to many different things so they can bind up bits of undigested food and other nasties.  In the lab, we try to make really specific antibodies, but it is often difficult.  In the case of AGEs, it's extremely difficult because AGEs can form on virtually any protein.  Some proteins may get modified with very many AGEs and others with very few.  Some proteins may be very big, some very small.  There is no one, specific shape of an AGE-modified protein and it is therefore impossible to make a highly specific, perfect antibody that precisely quantifies AGEs in foods.

By contrast, there are other ways to measure AGEs directly.  The gold standard is to use a technique called “liquid chromatography-tandem mass spectrometry with stable isotopic dilution.”  In short, this method digests the proteins in the food down to little itty bits so that all the individual AGEs are separated from their surrounding proteins.  The sample passes through a column that separates all the individual components.  As the AGE you are looking for plops out of the column, you determine exactly how much you have.  When you see reports using mass spectrometry, they report the AGE contents of foods in familiar terms like “milligrams.”  The drawback is that the method is more difficult, much more expensive, and that many labs are not equipped with the right machines.  The benefit is that the measurements actually reflect reality.

So what's the true CML content of butter as measured by mass spetrometry?  A study published last year showed that whole milk contains 40% more CML than butter.  Wow, big difference, huh?

Which do you believe?  The immunoassays that say butter has 5,000 times more CML than whole milk?  Or the mass spectrometry that says whole milk, which has more precursors, has 40% more CML than butter?

The same study found that evaporation of milk increased AGEs 10-fold, and that evaporated milk and various types of bread crust all had about 10 times the AGE content of butter and over five times the AGE content of beef.  Boiling beef increased the AGE content 7-fold, while frying the beef increased the AGE content 15-fold.

In addition to more posts on honey, fructose, and fatty liver, expect lots more information on AGEs in the coming months.

In the meantime, enjoy your butter!  Yum. :)