Wednesday, August 2, 2017

Oxidative stress, the pancreas, diabetes mellitus (type 2 diabetes), and proposed dietary helps

Time to make a couple suggestions, which partly grew out of considering the Navajo people, who now experience an extraordinarily high prevalence of type 2 diabetes on their reservation. ( The Navajo are closely related to the native Americans in the interior of Alaska, and it has been noted for some time that the traditional diet in the far northern parts of North America appears to protect against type 2 diabetes. (,

Over in Hungary, researchers have made an interesting discovery about catalase (an enyzme in our bodies that breaks hydrogen peroxide into water and oxygen): people who are genetically deficient in catalase develop type 2 diabetes more frequently and earlier. (, Hydrogen peroxide is one of the reactive oxygen species that cause oxidative stress, and oxidative stress is currently being looked at as a possible cause of people developing type 2 diabetes. ( Hydrogen peroxide in excess can induce cell death, and it travels readily through the extracellular matrix because it is a small molecule with a neutral electrical charge. ( What if excessive hydrogen peroxide (H2O2) is inducing death of the beta cells in the pancreas and bringing on type 2 diabetes? Recently published findings show that this could be exactly what is occurring:

Title: Chemistry and biology of reactive species with special reference to the antioxidative defence status in pancreatic β-cells.
Author: Lenzen S
Publication: Biochim Biophys Acta. 2017 Aug;1861(8):1929-1942. doi: 10.1016/j.bbagen.2017.05.013. Epub 2017 May 17.

Diabetes mellitus is a serious metabolic disease. Dysfunction and subsequent loss of the β-cells in the islets of Langerhans through apoptosis ultimately cause a life-threatening insulin deficiency. The underlying reason for the particular vulnerability of the β-cells is an extraordinary sensitivity to the toxicity of reactive oxygen and nitrogen species (ROS and RNS) due to its low antioxidative defense status.
This review considers the different aspects of the chemistry and biology of the biologically most important reactive species and their chemico-biological interactions in the β-cell toxicity of proinflammatory cytokines in type 1 diabetes and of lipotoxicity in type 2 diabetes development.
The weak antioxidative defense equipment in the different subcellular organelles makes the β-cells particularly vulnerable and prone to mitochondrial, peroxisomal and ER stress. Looking upon the enzyme deficiencies which are responsible for the low antioxidative defense status of the pancreatic β-cells it is the lack of enzymatic capacity for H2O2 inactivation at all major subcellular sites.
Diabetes is the most prevalent metabolic disorder with a steadily increasing incidence of both type 1 and type 2 diabetes worldwide. The weak protection of the pancreatic β-cells against oxidative stress is a major reason for their particular vulnerability. Thus, careful protection of the β-cells is required for prevention of the disease.

How do we protect the pancreas's beta cells from an excess of hydrogen peroxide? The pancreas is right in the middle of the abdomen, just under the stomach and flush against the duodenum. The duodenum is the first section of the small intestine and is the first location transited by food and digestive liquids after they leave the stomach.

It's been observed that visceral fat (fat around the internal organs of the abdomen) increases the risk of type 2 diabetes (, and it turns out that fat cells increase oxidative stress (, So the low-hanging (but hard-to-pick) fruit in the quest to not develop type 2 diabetes is to not be fat. Easier said than done, I know, but that's no reason to give up on working toward needed weight loss.

Another thing that can be done is to supplement the body's natural ability to break down hydrogen peroxide with consumption of active catalase and peroxidases (another kind of enzyme that breaks down hydrogen peroxide).

Catalase is in many plants and animals and is found in bovine liver; in fact, bovine liver is the source from which catalase was first isolated from back in 1937. ( Guess who ate raw liver and other organ meats? Yes, the circumpolar people's traditional diet included raw and dried organ meat (, meaning they consumed active catalase regularly and possibly helped protect their pancreatic beta cells from excessive hydrogen peroxide. If this connection I've just drawn has any merit, it cries out for a real study, for catalase now can be easily purchased as an inexpensive supplement which is purported to survive the low pH of the stomach. ( In general, I'm doubtful of claimed benefits from enzymatic and probiotic supplements because of absorption and inactivation issues, but for the narrow purpose of using catalase to protect the pancreas from hydrogen peroxide, catalase supplementation looks like a plausible prophylactic.

While writing my recently published hypothesis paper on horseradish and radish peroxidases (, I read a lot about vegetable and fruit peroxidases. The longer peroxidase enzymes sit in an acidic environment, such as that of the stomach, the more the peroxidase enzymes become denatured and ineffective at breaking down hydrogen peroxide. The speed at which they become inactive varies amongst plants, but green beans seem to have more persistently-active peroxidases than several other plants. (, (Unfortunately, people usually cook green beans before eating them, although they taste fine raw.) Sometimes acid-denatured peroxidase enzymes can become regenerated to an extent after being removed from the acidic environment. ( Happily for us, the duodenum pH is neutral or slightly alkaline, meaning that it might provide an environment in which acid-denatured peroxidases can become temporarily active again.

Image from Allegheny Nutrition: The Enzyme Specialists;

Therefore, the active plant peroxidases we eat have a chance of being active to some extent in the duodenum where they can help break down hydrogen peroxide before it damages pancreatic beta cells. This possibility fits with the reported link between low intake of fruit and vegetables and an increased risk of developing type 2 diabetes. ( So eat fresh--because many forms of preservation use heat and acids specifically to inactivate peroxidases--and reconstituted-after-being-dried fruits and vegetables to avoid developing type 2 diabetes.

The Navajo Nation did the right thing in in 2013 when it tried to remove sales tax on fresh produce, but unfortunately that legislative effort was vetoed. ( Last week I purchased food on the Navajo reservation, and they taxed my graham crackers and my tomatoes at the same rate. The health act veto was unfortunate and short-sighted, in my opinion, and is likely continuing to depress sales of fresh produce on the Navajo reservation; even my young children noticed how out-of-the-way the small produce section was in reservation grocery store compared to our huge, at-the-entrance produce sections of supermarkets in urban Colorado. The traditional Navajo diet included uncooked plants and dried meat--likely sometimes liver meat with high catalase content--and modern Navajos are not getting enough of these foods.

Take a lesson from Weird Al Yankovic, and love your pancreas to lessen your risk of type 2 diabetes.* Don't surround it with extra adipose tissue, and give it lots of help breaking down hydrogen peroxide by consuming catalase and peroxidases (especially ones that are resistant to denaturing by acidic environments).

"Pancreas" - Weird Al Yankovic (you'll thank me later)

* I know some who read this are going to think that I'm far too optimistic about the above suggestions making a difference in type 2 diabetes, but it's relatively uncontroversial that exercise (which leads to loss of abdominal fat-- and improving one's diet can "reverse" type 2 diabetes. ( My Hispanic grandmother successfully put her type 2 diabetes in remission decades ago and ended up dying much later from dementia after decades of staying active and following the advice in Prevention magazines (of which she had a lot lying around her house). Don't be fatalistic. Diabetes mellitus is not a destiny you can do nothing about.

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