Repair your DNA

[mcsblues]

Interesting story on the ABC's (Australia) Catalyst tonight involving the importance of folate and B12 in repairing damaged DNA. They say that 90% of Australians don't get enough - one would imagine other western countries would be similar - and in the absence of sufficient dietary sources - supplementaion is a very easy, and in this case a cheap and amazingly effective solution.

The transcript is attached - be warned you might emit a small scream of disgust about half way through, when the reporter dismisses one good dietary source ... yes of course, my email is on its way!

2 June 2005
We all know that as we get older, we start to wear out. Even our most individual blueprint for life, our DNA, becomes progressively more damaged as we get older. And damaged DNA can be the starting point for several degenerative diseases and cancer. Now someone is looking out for the health of your DNA and the good news is, you can do something about it.

Transcript
Narration: Getting older means wearing out.
But it's not just muscles, joints and organs that suffer.
The older we get, the more damage we do to our own individual blueprint for life: our DNA. And the consequences of a lifetime's DNA damage could be a range of degenerative diseases and cancers. But now this man has made the health of your DNA his top priority.

Dr Michael Fenech: We should consider damage to the genome as a fundamental disease that can be diagnosed and treated.
Narration: And the good news is, we can all take simple steps toward a healthier genome.
Dr Michael Fenech: We know that to some degree it depends on the genes you inherit. However, we also know that you can actually reduce that rate of genome damage.
Narration:This could be the biggest breakthrough in preventative medicine since the discovery of vaccination. Working in the CSIRO's Health Sciences division, Michael has been looking at how a range of simple treatments can effect the health of our DNA And I'm about to become a guinea pig to test Michael's theories.
He claims that one particular treatment can actually help repair damaged DNA.
But the first step is to look at my DNA and see how much damage I've done to it over the last 40 years. With a little persuasion my white blood cells are made to divide. In each cell's nucleus the strands of DNA are supposed to make nice neat copies - but sometimes things go wrong.
Dr Michael Fenech: We've been looking for abnormalities and the shape of those nuclei and then the formation of small nuclei called micro-nuclei where the aberrant DNA or the broken DNA tends to be located.

Narration: If the DNA is damaged, the nucleus doesn't divide cleanly into two equal parts. Michael counts the number of these bad copies from 1000 cells.

This gives him a rate for my personal DNA damage which he can then compare to typical rates of DNA damage in people my age. And the results are encouraging!

Dr Michael Fenech: Well we've had a look at your results and that yellow dot over there is you.

Dr Paul Willis, reporter: So I've actually got quite low damage.

Dr Michael Fenech: You are actually tracking not too badly for your age.

Dr Paul Willis, reporter: So there is actually one index on which I'm actually relatively healthy.

Dr Michael Fenech: You are actually doing quite well on this index, although not as well as an 18 or 25 year old.

Dr Paul Willis, reporter: Right.

Dr Michael Fenech: But that would be interesting to see whether it were possible to bring that rate down to somebody who's 20 years younger.

Narration: So, even though my DNA is already in a pretty healthy state, Michael thinks it's possible to undo some of the DNA damage I have already done to my genome.

That's a remarkable claim and I have to admit, I'm sceptical.

So I'm off to Professor Bruce Armstrong at the University of Sydney. He'll know if really is possible to undo some of my DNA damage.

Professor Bruce Armstrong: I think the answer to that is in principle, yes. We do know that there's a dynamic process going on here where DNA has been damaged, DNA is being repaired, damaged DNA is being eliminated from the body and so on and if you can slow down the rate at which DNA damage occurs then you will improve the state of your DNA.

Narration: So time to take the good Doctor's challenge. And the treatment is a pretty simple one.

According to Michael, DNA has its' own set of rebuilding tools built into it's structure but they can't do their job effectively unless there is plenty of folate and B12 around.

Alarmingly, around 9 out of 10 Australians do not have enough folate in their diets to provide for the basic cell functions of DNA replication and repair.
Dr Paul Willis, reporter: By far the best source of dietary folate are chicken livers, fried of course, but I have a cholesterol problem and so these guys are off the menu. If I want to go to vegetables, broccoli and brussel sprouts are great, but I'd still need to eat half a kilo a day to get the folate I need, and I think my wife and friends might complain about the side effects. So I've decided to take pills instead.

Narration: I'll need about 500 micrograms folate or folic acid and 50 micrograms of vitamin B12 daily to help with the DNA rebuilding work.

And, for three months I stuck to the plan. No matter where I went, I faithfully took my folate and B12 every day.
And after three months, I'm itching to know if my DNA has improved!

Dr Paul Willis, reporter: Have I done anything?

Dr Michael Fenech: Yes well it looks like the supplements you were taking have had an effect on the rates of DNA damage in your cells.

Dr Paul Willis, reporter: What sort of impact?

Dr Michael Fenech: Well we observed about a 45% reduction.

Dr Paul Willis, reporter: 45%?

Dr Michael Fenech: Yes.

Dr Paul Willis, reporter: That sounds very good.

Dr Michael Fenech: It's pretty good. The largest reduction was in this type of damage which is actually pretty important because it's thought to create the genomic instability that leads to the genetic changes that initiate cancer.

Narration: This is great news for me - particularly seeing as there are some rather nasty cancers lurking in the family history.

But, once again, the news sounds almost too good to be true. So it's back to Prof Armstrong to put my results into context.

He's already found folate can have an amazing effect in children.

Professor Bruce Armstrong: If we can see a 60% reduction in risk of a childhood cancer possibly as a result of folate in pregnancy. Now your 45% reduction in DNA damage doesn't sound all that implausible.

Narration: Back in Adelaide Michael has big plans for his research findings.

He's proposing the establishment of Genome Health Clinics where people can fine-tune their vitamin consumption to suit their own individual DNA.

And such a clinic would not have to be buried away inside a huge hospital...

Dr Michael Fenech: You could go to the clinic, give your blood sample and after three months to find out whether the change you have made for your diet has actually caused you any benefit or might have caused you harm.

It could possibly be a shop front in Rundle Mall, definitely.

Narration: So in the not too distant future, busy people will be able to participate in this break through in preventative medicine with a simple blood test in a shop-front clinic.

And if my own experience is anything to go by, it will be a simple and painless process that could help prevent some serious illnesses down the track.

http://www.abc.net.au/catalyst/stories/s1381311.htm

Cheers,

Malcolm

[VALEWIS]

So why not just take folate and B12 and skip the DNA blood tests?

Val

[mcsblues]

I do - but its nice to see what a dramatic effect that simple step can cause.

I also eat liver! ;)

Cheers,

Malcolm

[VALEWIS]

Yes, but the thrust of the show was 'Gee soon we will be able to go get our DNA blood test at the corner store." And then we will know if we need to take folate and B12.

Let us know if you get a reply to your email to them re the fried chicken livers and cholesterol etc

V

[mcsblues]

Interesting. Apart from the cholesterol nonsense, I didn't get that slant on the program. the before and after DNA tests seemed designed to illustrate the amazing difference simple supplementation makes in this case. Nevertheless if you take away all the big brother and health insurance worries about other peoples' knowledge of your genetic makeup - that "corner store" DNA test may well become very helpful to individuals (and perhaps their hopefully enlightened doctors) when fine tuning your low carb diet with or without added supplements. If this information made you aware of your sensitivity or mild intolerance to certain foods for example - which currently are not detected by today's allergy testing.

Cheers,

Malcolm

PS. Folate is one of those supplements which is highly promoted for women - particularly pregnant women or those that may become pregnant - for good reason. But you rarely, if ever see the considerable benefits highlighted for the rest of us.

[AJCole]

I hate liver, chickens or otherwise. Are there any other animal sources (hate broccoli, too) of folate?

[mcsblues]

" Good food sources of folic acid include asparagus; beets; broccoli; avocados; Brussels sprouts; beans, dried; chickpeas; soybeans; lentils; oranges; peas, fresh; turkey; cabbage, savoy; bok choy; and spinach."

http://www.wholehealthmd.com/refshelf/substances_view/1,1525,887,00.html

This article is one of the very few I found that suggests that folate is vital for all of us - not just women who are/might become pregnant. Given the long lists of benefits (headed by CHD and Altzheimers prevention) plus the possible loss of this water soluable vitamin through cooking, not to mention the original story's suggestion you would need to eat half a kilo (1.1 pounds) of brocoli etc a day ... a daily supplement of folate and B12 seems the easiest and safest solution (as well as eating plenty of green leafy vegetables).

Cheers,

Malcolm

[Dodger]

What happened to B6? Most articles I have read have had the holy trinity of folate, B6 and B12.

[Turtle2003]

What happened to B6? Most articles I have read have had the holy trinity of folate, B6 and B12.

Yes, and aren't we supposed to take a supplement that has a proper balance of all the B vitamins?

A very, very interesting post. I don't think I've ever read anything that showed such easily quantifiable results of vitamin/nutrient supplementation.

Edit: I just thought of something. This article should cause some concern for a Vegan.

[mcsblues]

Yes, I do take a B complex supplement which contains B12 and B6 along with a small amount of folate. I do take a separate folate supplement as the common recommendation is generally 400 - 1000 micrograms (the program said 500) - (my B complex contains 99 micrograms) I don't feel the need for separate B12 and B6 supps as a good low carb diet should have plenty in the meat, fish, eggs and leafy greens we eat. A vegan would have to supplement for B12 at least.

Cheers,

Malcolm

[mcsblues]

Gabriel Guzman's (PP forum) interesting take on this;

"Very interesting, thank you!!

When I read about folate in that transcript, I couldn't help but asking myself "what's the link?"

Folate deficiency of impairment in its metabolism is associated with hyperhomocysteinemia (in turn associated with cardiovascular disease) and more important, folate metabolism impairment is associated with something called hypomethylation which in turn impairs DNA repair and biosynthseis. So, folate deficiency is associated with DNA damage, impaired cell proliferation, malignancies and as we'll see below, impaired production of something called endothelial nitric oxide.

Then I remember an article published in 2003 in Cardiovascular Diabetology that talked about type 2 diabetes being a vascular disease (atheroscleropathy) and focused in the role of nitric oxide (NO) in the vascular system.

To give you a short background, nitric oxide became famous in 1992 (voted molecule of the year by Science Magazine) and even more famous in 1998 when a Nobel Prize in Medicine and Physiology was awarded to three scientists for their discoveries concerning nitric oxide as a signaling molecule in the cardiovascular system. Nitric oxide is produced by a family of enzymes called nitric oxide synthases (NOS). There are three different isoforms of these enzymes, neural NOS-1 (nNOS), inducible NOS-2 (iNOS) and endothelial NOS-3 (eNOS) and each one of them makes NO for a particular purpose. One can divide these three enzymes in "beneficial" or "detrimental" depending on the actual metabolic status. In general, however, nNOS and eNOS are beneficial because NO is produced as part of a protective mechanism against oxidative damage, anti-inflammatory, anti-fibrotic, just to mention a few of their roles. iNOS, on the other hand is involved in immune defense mechanisms, which one might think is a good thing and just what we want as NO produced by iNOS kills invading organisms. So, iNO (the product of iNOS) can be thought as an inflammatory NO. Paradoxically, in both acute and chronic inflammatory states iNO also kills the native hosts cells in the immediate surrounding area. So, too much iNO is not a good thing and that's why we tend to think of iNO as detrimental if in excess.

Ok... where does all this go and what does it have to do with folate? It turns out that in the vascular endothelium (i.e. the cells that make up the arterial vessel wall), where eNOS is expressed is a net producer of eNO, which is a powerful antioxidant. Thus, a healthy endothelium produces eNO, whereas a dysfunctional endothelium produces something else; superoxide (O2'). Superoxide is a powerful oxidant and responsible for much of the oxidative damage in the arterial wall that occurs during the development and progression of atheroscleropathy (this is by the way the accelerated atherosclerosis observed in and associated with metabolic syndrome, insulin resistance, prediabetes nd overt type 2 diabetes which is driven by reactive oxygen species associated with multiple toxicities). All that means that anything that can compromise the production of eNO will also affect the normal function of the vascular endothelium.

The "eNOS" reaction, that is the system that involves the eNOS enzyme to produce NO in the endothelium, includes arginine as a substrate. Arginine is an amino acid present in proteins. Arginine is "processed" to produced NO and another amino acid, citrulline, which is not a naturally ocurring one. If everything is normal, then NO is produced but when things are not well, then instead of NO, it is O2' (superoxide) what is produced in the reaction. When that happens, we say that the eNOS reaction is "uncoupled".

Another compnenet of the reaction include another enzyme that uses a "co-factor" (an aid if you will) so it can do its work more efficiently. This other enzyme's name is NAD(P) Oxidase. You don't need to remember this name. Just remember that the "aid" for this enzyme, which we will call BH4 is essential to couple the eNOS reaction, in order for arginine to be oxidized to NO and citrulline. So, if BH4 is not present, then the eNOS reaction is impaired and instead of NO, we end up with O2'.

There are at least 4 ways ways to uncouple (in easy words... mess up with) the eNOS reaction. I won't go into the details of three of them but I will explain the one that pertains to folate directly. As I wrote above, BH4 is essential for the eNOS reaction to proceed in the direction of NO production. If BH4 is not functioning properly the entire eNOS reaction becomes a net producer of superoxide. And guess what, folate supplies electrons to restore BH4 during the eNOS reaction. I could just said that at the beginning but then you would be wondering what on Earth is eNOS and BH4...

So, following the chain of ideas... if folate is deficient, then the eNOS reaction is uncoupled and the endothelium (which is everywhere) becomes a net producer of superoxide, a powerful oxidant, which in turn can turn the endothelium dysfunctional. An increase in oxidative species can also affect DNA so now we see another possible way in which folate is involved in keeping DNA safe from damage and its repair mechanism working smoothly.

As a side note, guess what factors or toxicities affect the eNOS reaction?


* Advance Glycosylation/fructosylation products (also called AGEs)
* Ageing (nothing we can do about this one!)
* Antioxidant reserve compromised
* Free fatty acid toxicity (probably more important in uncontrolled diabetes)
* Insulin toxicity (hyperinsulinemia)
* Glucotoxicity (compounds peripheral insulin resistance)
* Hypertension
* Triglyceride toxicity



In all but one, we can do something about it, and we now know how... don't we?"