Wednesday, March 10, 2010

I wasn't kidding. Your antioxidants are trying to kill you.

So you've got this creature. It's a weird thing. It doesn't make vitamin c. It lacks uricase, so instead of peeing allantoin, the oxidized form of uric acid, it pees uric acid itself. This leaves the creature susceptible to a number of things. The vitamin c, scurvy. The high levels of uric acid can make gout a problem, if the diet isn't right.
One thing a creature with low levels of vitamin c needs, besides vitamin c; a system to preserve vitamin c. Linus Pauling observed that sick or wounded animals have elevated levels of vitamin c. Scar tissue has high levels of collagen; vitamin c is needed for the maintenance of collagen. One of the lovely consequences of scurvy is old wounds opening up; broken bones that have long healed will even separate. The tough collagen, an adaptation that should improve the strength of the repair, has become a weakness. So, Pauling's theory was that Lp(a), a lipoprotein that is increased in people in heart disease (and also, according to Peter, in very young infants) is a surrogate for vitamin-c collagen formation. So heart disease is a form of low-grade, prolonged scurvy caused by excessive dependence on the Lp(a) patch to repair arteries. So eating lots of vitamin C (and other nutrients, like lysine, of which collagen is composed) should prevent and reverse heart disease.

How to preserve vitamin c? Well, there's these glut-doohickeys which I understand are somehow involved in the uptake of both glucose and vitamin c, and our doohickeys seem to be set up to keep vitamin c in the system. I direct you to the world wide web if you want to know more about those.

Here's another way; healing demands collagen formation, which demands vitamin c. Even uses it up. When vitamin c is in short supply, it's awfully valuable, you don't want to waste it. Maybe you use up your vitamin c healing a major wound, you wind up with scurvy. Trying to heal is killing you. So you need a way to ration your resources so that the tissues under the most repeat stress (artery branches, etc.) get the collagen they need to toughen up, while avoiding scurvy in the whole body.

Enter uric acid, allantoin, lp(a) and maybe Neu5Gc.

Here's how I see it; "

Edit; how I see it is largely my understanding of what Peter (Hyperlipid) has been explaining it on his blog. The uric acid thing is my fixation.

An artery is wounded. Lipoproteins (ldl "bad" cholesterol) is drawn to the injury site. Ldl cholesterol is a lipoprotein that delivers fat and cholesterol to places where it's needed.

Artery endothelial cells (the cells that make up the inner lining of arteries) have receptors for ldl.
Endothelial cells have mitochondria, which help the cells produce energy from fatty acids or glucose. When mitochondria are happily chomping away on fats, they start spewing out reactive oxygen species, free radicals. The thing about reactive oxygen species is, they tend to oxidize things. Like, for instance, uric acid. Which produces allantoin. Which is, um, permissive of endothelial cell proliferation. Which is, um, pretty obviously a healing process.

What kind of fat do you want fed into your endothelial mitochondria when it's time for some healing?

Well, here's an interesting bit about fish oil vs corn oil;

An increase in reactive oxygen species by dietary fish oil coupled with the attenuation of antioxidant defenses by dietary pectin enhances rat colonocyte apoptosis
Auteur(s) / Author(s)SANDERS Lisa M. (1) ;
HENDERSON Cara E. (1) ; MEE YOUNG HONG (1) ; BARHOUMI Rola (2) ;
BURGHARDT Robert C. (2) ; NAISYIN WANG (3) ; SPINKA Christine M. (3) ;
CARROLL Raymond J. (1 3) ; TURNER Nancy D. (1) ; CHAPKIN Robert
S. (1) ; LUPTON Joanne R. (1) ;
Affiliation(s) du ou des auteurs /
Author(s) Affiliation(s)(1) Faculty of Nutrition, Texas A&M University,
College Station, TX 77843, ETATS-UNIS(2) Department of Veterinary Anatomy and
Public Health, Texas A&M University, College Station, TX 77843,
ETATS-UNIS(3) Department of Statistics, Texas A&M University, College
Station, TX 77843, ETATS-UNIS
Résumé / AbstractWe showed previously that the dietary combination of fish oil, rich in (n-3) fatty acids, and the fermentable fiber pectin enhances colonocyte apoptosis in a rat model of experimentally induced colon cancer. In this study, we propose that the mechanism by which this dietary combination heightens apoptosis is via modulation of the colonocyte redox environment. Male Sprague-Dawley rats (n = 60) were fed 1 of 2 fats (corn oil or fish oil) and 1 of 2 fibers (cellulose or pectin) for 2 wk before determination of reactive oxygen species (ROS), oxidative DNA damage, antioxidant enzyme activity [superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx)] and apoptosis in isolated colonocytes.

Fish oil enhanced ROS,

whereas the combination of fish oil and pectin suppressed SOD and CAT and enhanced the SOD/CAT ratio compared with a corn oil and cellulose diet. Despite this modulation to a seemingly prooxidant environment, oxidative DNA damage was inversely related to ROS in the fish oil and pectin diet, and apoptosis was enhanced relative to other diets. Furthermore, apoptosis increased exponentially as ROS increased. These results suggest that the enhancement of apoptosis associated with fish oil and pectin feeding may be due to a modulation of the redox environment that promotes ROS-mediated apoptosis.

Do not eat corn oil; beware plant fats high in omega-6 fatty acids in general. Fish oil seems like a very good idea, if you're depending on your blood lipids to ensure that your arteries are healed properly.

Pectin works as an anti-anti-oxidant (pro-oxidant) in the colon? Pretty freakin' cool. Those studies with anti-oxidants, the disappointing ones where vitamin c led to carotid artery thickening, where beta-carotene supplemented smokers got more cancer. Here's what Health Canada has to say about the dangers of vitamin e supplementation;

Recently published studies have suggested that vitamin E supplements not only fail to prevent heart disease and cancer, but may actually harm people who take high doses over a long term. However, these studies are limited by the fact that they involved: people 55 years or older who already had heart disease or diabetes; people with cancer or who previously had cancer; and people who may be at higher risk of developing these diseases.
One study found that patients with heart disease or diabetes who took 400 IU of vitamin E daily for an average of seven years were at a significantly increased risk of
heart failure compared to patients who were not taking vitamin E supplements. This study concluded that high-dose vitamin E supplements (400 IU or greater) should not be taken by patients with heart disease or diabetes.
In another study, daily doses of 400 IU of vitamin E were given to patients receiving
radiation therapy for cancers of the head and neck. The theory was that the antioxidant treatment might reduce the incidence of additional cancers of the same type among these patients. However, it was found that those who received vitamin E supplements were significantly more likely to develop other similar cancers during the supplementation period than those receiving a placebo.

ApoE is a lipoprotein tingy that carries certain fat soluble nutrients around in the blood stream. Antioxidants all. These have a place in the healing and maintenance of the body. But there's a time to oxidize, and then there's a time to anti-oxidize. The ApoE-4 genotype is more prone to heart disease, alzheimers, various cancers, etc. Misdelivery of these vital antioxidants could pretty obviously be dangerous, in light of the importance of reactive oxygen species to the healing and to the cancer-fighting processes.

Vitamin k is an antioxidant. Human atherosclerotic plaque is generally calcified, at least in Western populations. Vitamin k is important to calcium homeostasis-- including the removal of calcium from soft tissues, artery walls, etc. Maybe a bit of a catch-22 there.


donny said...

I should have mentioned something very obvious here. ApoE is also how vitamin e is transported in the blood, that's where the "e" comes from.
Wayfarin blocks some actions of vitamin k; calcium accumulates in soft tissues as a result. This effect can be reversed (at least in the mice in the old study I'm vaguely remembering) by either large doses of vitamin k or vitamin e.

It seems reasonable to suppose that calcification of atherosclerotic plaque might occur because the body doesn't dare deliver vitamin e to the area-- the tissues are already having more than enough trouble burning fat for energy, delivery of an antioxidant that discourages the process further would be horrible reckless.

donny said...

Looks like I should have said delivered rather than carried; think various ports, ApoB, E, etc. on an ldl particle.