Thursday, August 22, 2019

New Hypotheses

Sometimes it seems as if almost everything I was taught in school is now considered wrong. Well, OK, not everything. The letter i still usually comes before e, except after c and a ton of other exceptions including neither leisured foreigner seized the heifer on the weird heights, and no one cares about spelling today anyway.

Of course in science, no theory is permanent. New evidence requires updating of current theories, somethings reversing them completely.

I just hope no one discovers that the universe isn't expanding, but imploding toward another Big Bang! And if it is, I hope it doesn't occur in my lifetime.

But on a more mundane level, three papers came in recently that are challenging accepted dogma.

The first suggests that lactate, a product of metabolizing glucose, isn't a dead-end molecule produced only when there isn't enough oxygen to metabolize it further, but rather is an important source of energy and a way to distribute this energy from one tissue to another. George Brooks of the University of California, Berkeley, has been proposing this idea for 40 years, but no one has been paying much attention, and most biochemistry sources still show it as a sort of waste product produced only in the absence of oxygen and causing pain after heavy exercise.

But the Brooks lab found that lactate is actually a preferred source of energy in some tissues like the brain and heart. Brooks calls the production, transport, and use in various tissues the lactose shuttle.

The whole review can be seen here.  

A second paper  suggests that it's not a lack of insulin but insulin hypersecretion that causes insulin resistance and type 2 diabetes. Australian researcher Christopher Nolan is one of the authors of this paper, and I've written about some of his ideas before, namely the idea that insulin resistance is protective for some tissues.

Nolan and his coauthor support the idea that there are five subtypes of diabetes and says that the type that causes insulin hypersecretion is severe insulin-resistant diabetes (SIRD). If someone has this kind of type 2 diabetes, then he says treating it with insulin injections or sulfonylureas would be counterproductive.

People with other subtypes might benefit from such treatments.

I suspect that researchers will eventually discover even more subtypes of diabetes, with some overlap, but for now we can stick to just five. Nolan says it's "time for a conceptual framework shift" to consider the main driver of type 2 diabetes to be not insulin resistance but insulin oversecretion. It's an interesting way of looking at the disease.

Finally, the third paper says that it isn't high glucose levels but defects in mitochondria and elevations in some fat derivatives and their processing in the defective mitochondria that cause inflammation. The senior author of the paper, Barbara Nikolajczyk, kindly sent me the full text, but the research is so complex I can't evaluate it and have to accept the summaries. There are 20 authors, and you can see the summary here.

In the past, there have been studies relating high blood glucose levels and inflammation, but as we all know, correlation is not causation, and it's not always clear if the high A1cs caused the inflammation or if inflammation caused the  high A1cs, or if a third factor caused them both. One study even suggested that low blood glucose levels, but not high blood glucose levels, caused inflammation in monocytes (a type of white blood cell). The Nikolajczyk study used peripheral blood mononuclear cells, which include monocytes and a few other cell types.

New hypotheses usually stimulate new research and often result in significant advances. Maybe I should  hypothesize e before i, don't ask me why, except for most words, that are known by all nerds and maybe I'd start a spelling revolution. At least no one would be hurt in such a revolution.

Friday, August 2, 2019

Does Paleo Diet Increase Risk for Heart Disease?

A recent flurry of articles in the popular press claim that following the Paleo diet causes an increase in your risk of  heart disease, primarily because of a molecule called TMAO (trimethylamine N-oxide).

Most people agree that the bacteria in your colon convert carnitine, found in red meat, to TMAO. How dangerous this is, however, is not as clear, and several  bloggers have detailed why they don't think we should lose sleep about TMAO, so I won't repeat their analyses.

Two things I think should be emphasized: (1) resistant starch increases TMAO and (2) some fish increase TMAO.

The author of the recent study emphasized the lack of whole grains in Paleo diets, saying, "We know that whole grains are a fantastic source of resistant starch." But wait! Resistant starch increases TMAO levels.

Another study even suggests that vegetables can increase TMAO levels and increased TMAO levels are helpful in heart failure.

I think we don't know enough about the relation between TMAO and heart disease to make any dietary changes according to what increases or decreases its levels. Fish and resistant starch are supposed to be healthy but they both can increase TMAO. Some people think red meat is unhealthy, but it can increase TMAO.

I think the publicity about the Paleo diet and TMAO is an example of some people thinking that any diet that doesn't follow the recommendations of the Dietary Guidelines for Americans is a fad diet and then looking for reasons to avoid it.

I remember one nutritionist criticizing low-carb diets because "They don't provide the 60% carbohydrate content recommended by the DGA." Um, isn't that what "low-carb" means? Sometimes I wonder where such people learned to think. . . if they ever did.

So I'd say one shouldn't lose sleep over TMAO. Eat what works for you to keep your blood glucose levels as close to normal as you can, keep an eye on your blood pressure and blood lipid levels, and don't panic over every flashy headline that appears in the popular press.