James Watson proposes a radical new explanation for disease and inflammation. Hydrogen peroxide, an oxidant, helps new proteins stabilize their shape as they emerge from the endoplasmic reticulum. If you take too many antioxidant supplements (as I probably do), proteins emerge unfolded and that causes inflammation.
... Nobel laureate James D. Watson, the co-discoverer of the double-helix structure of DNA, ... His latest, ... hypothesis on the causation of type 2 diabetes, suggests that diabetes, dementias, cardiovascular disease, and some cancers are linked to a failure to generate sufficient biological oxidants, called reactive oxygen species (ROS).
"The prevalent view of type 2 diabetes," Dr. Watson says, "is that an excess of intracellular oxidation causes inflammation, which in turn kills cells in pancreatic tissue." Proper function of those cells, it is well understood, is critical for the maintenance of normal blood glucose levels.
Over the last several years Watson has been puzzling out an alternative view, based on facts reported in the peer-reviewed literature of medicine and molecular biology. (He makes clear that he is not a medical doctor, rather a student of science.) He does not question that pancreatic tissue in people with type 2 diabetes is indeed inflamed. But he does present a novel theory of why. "The fundamental cause, I suggest, is a lack of biological oxidants, not an excess," he says.
In a cellular organ called the endoplasmic reticulum (ER), one such "species," the oxidant hydrogen peroxide (H2O2), helps forge chemical bonds (disulfide bonds) which stabilize proteins as they fold.
When there is not enough oxidation in the ER, Watson says, proteins emerge unfolded, and cannot function. This, he proposes, causes the inflammation that harms the pancreas, sometimes causing type 2 diabetes. Hence, Watson suggests, exercise, which promotes oxidation, plausibly can have a beneficial effect on those with high blood sugar. Such benefit would be lessened if not abolished, he speculates, if such an individual consumed large quantities of antioxidants -- just as athletes who take large quantities of antioxidant supplements do not seem to benefit or benefit less from their exertions. [emphasis mine]
About 15 years ago, I stopped taking large amounts of antioxidants and vitamins, because the medical community seemed to agree that it was of no benefit and probably harmful.
About 4 years ago, I stopped taking antioxidants and vitamins entirely because Consumer Reports on Health kept saying the studies show they were unnecessary if one eats a reasonable diet.
I used to take 5000 mg of vitamin C per day because Linus Pauling bragged it up so much. I noticed at about the time I started taking it, my frequency of colds dropped from 4 per year to 1 per year.
However, since I stopped taking it, my cold frequency is still 1 per year. It must have been coincidence. Perhaps my immune system became better able to fight colds at that time, or some explanation other than vitamin C.
Quackwatch has an article on Pauling. He has been involved in quite a few questionable activities:
Spud, excellent article. I am reposting on Twitter.
Interesting article. Thanks, and reposting on Twitter.
"Watson has two take-home messages for his audience. "The first is that we sorely need to take a much more serious and thorough scientific look at the mechanisms through which exercise improves our health." Watson is planning a scientific meeting at Cold Spring Harbor Laboratory later this year which he hopes will launch a larger scientific effort.
"There is a second message. "I am not a physician and I cannot offer advice about how people should treat their diabetes; I am advancing a novel idea about how type 2 diabetes can occur. But I also note that just about every doctor I've ever known tells every patient who is capable of doing so to exercise. I think exercise helps us produce healthy, functional proteins. But we really need to have some high quality research to demonstrate this."
Is Watson qualified to make speculations of this sort?
Also, speculations abound ... New Scientist magazine is composed of interesting speculations. They are closer to reality than science fiction is, but that's not saying much.
Weighing in on the antioxidant question, the mechanism by which free radicals in the liver contribute to type 2 diabetes, obesity, and fatty liver has been uncovered.
An international team of scientists led by Monash University researchers has shown how free radicals contribute to type 2 diabetes, obesity and fatty liver disease. Type 2 diabetes and non-alcoholic fatty liver disease are key complications of obesity as 80 per cent of patients with type 2 diabetes are obese, and 75 per cent of patients who are obese or have type 2 diabetes also have fatty liver disease.
The team, led by Professor Tony Tiganis from the Department of Biochemistry and Molecular Biology at Monash, has found that free radical molecules called Reactive Oxygen Species (ROS) wage a battle with enzymes called protein tyrosine phosphatases, initiating a cascade of events with devastating consequences.
The findings, published in the journal Cell Metabolism, explain how selective insulin resistance -- a pathological feature of type 2 diabetes -- occurs in the liver. The study identifies the molecular culprits involved, and reveals how they contribute to disease progression.
"We have shown for the very first time that these free radicals inactivate protein tyrosine phosphatases in the liver to activate rogue pathways that promote fatty liver disease and exacerbate the development of obesity and type 2 diabetes," Professor Tiganis said.
Professor Tiganis' team found in lab studies that obesity promoted ROS generation that inactivated a phosphatase called PTPN2. This inactivation in turn exacerbated obesity and fatty liver disease progression.
While free radicals play important roles in disease, Professor Tiganis advises against taking anti-oxidants indiscriminately. [emphasis mine]
While I'm not taking tons of anti-oxidants, I think MitoQ might be helpful here, because it can enter the mitochondria of the liver, where free radicals are generated.
Weighing in on the health-promoting effects of antioxidants, new research shows inflammation directly leads to accelerated aging.
Chronic inflammation has long been associated with age-related disorders but whether it is causing aging or caused by aging was unclear. Now in a recent study scientists at Newcastle University collaborating with an international team have demonstrated that chronic inflammation accelerates aging.
The causal link between chronic inflammation and aging was discovered to be through the telomeres, a well-known age-related part of DNA. To show this the authors started by removing a “brake” protein in mice that keeps inflammation under control called nfkb1. The removal of this protein makes the mouse acquire chronic, low grade inflammation.
At only 36 weeks of age, the mice with chronic inflammation displayed classic hallmarks of aging that were prominent only much later at 132 weeks of age in normal mice, including early graying, increased scruffiness and loss of fur, reduced fat stores, diminished tissue regeneration, and enlarged hearts. This unequivocally showed that chronic inflammation leads to accelerated aging. Treating mice with anti-inflammatory drugs like ibuprofen improved some conditions. More importantly, treating with an anti-oxidant showed the same rescue effect, strongly suggesting that inflammation was exerting its effects classically through reactive oxygen species, i.e. highly reactive molecules that cause chemical damage. [emphasis mine]