Autoimmune Thyroid Disease

An Unfortunate and Lengthy Adventure in Misdiagnosis

Studies force new view on biology of flavonoids

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Chris has come up with the goods again and has sent me another great news story! At last some sanity appears to have returned to the vegetable antioxidant researchers:

CORVALLIS, Ore. – Flavonoids, a group of compounds found in fruits and vegetables that had been thought to be nutritionally important for their antioxidant activity, actually have little or no value in that role, according to an analysis by scientists in the Linus Pauling Institute at Oregon State University.

However, these same compounds may indeed benefit human health, but for reasons that are quite different – the body sees them as foreign compounds, researchers say, and through different mechanisms, they could play a role in preventing cancer or heart disease.

Based on this new view of how flavonoids work, a relatively modest intake of them – the amount you might find in a healthy diet with five to nine servings of fruits and vegetables – is sufficient. Large doses taken via dietary supplements might do no additional good; an apple a day may still be the best bet.

A research survey, and updated analysis of how flavonoids work and function in the human body, were recently published in Free Radical Biology and Medicine, a professional journal.

“What we now know is that flavonoids are highly metabolized, which alters their chemical structure and diminishes their ability to function as an antioxidant,” said Balz Frei, professor and director of the Linus Pauling Institute. “The body sees them as foreign compounds and modifies them for rapid excretion in the urine and bile.”

Flavonoids are polyphenolic compounds with some common characteristics that are widely found in fruits and vegetables and often give them their color – they make lemons yellow and certain apples red. They are also found in some other foods, such as coffee, tea, wine, beer and chocolate, and studies in recent years had indicated that they had strong antioxidant activity – and because of that, they might be important to biological function and health.

“If you measure the activity of flavonoids in a test tube, they are indeed strong antioxidants,” Frei said. “Based on laboratory tests of their ability to scavenge free radicals, it appears they have 3-5 times more antioxidant capacity than vitamins C or E. But with flavonoids in particular, what goes on in a test tube is not what’s happening in the human body.”

Research has now proven that flavonoids are poorly absorbed by the body, usually less than five percent, and most of what does get absorbed into the blood stream is rapidly metabolized in the intestines and liver and excreted from the body. By contrast, vitamin C is absorbed 100 percent by the body up to a certain level. And vitamin C accumulates in cells where it is 1,000 to 3,000 times more active as an antioxidant than flavonoids.

The large increase in total antioxidant capacity of blood observed after the consumption of flavonoid-rich foods is not caused by the flavonoids themselves, Frei said, but most likely is the result of increased uric acid levels.

But just because flavonoids have been found to be ineffectual as antioxidants in the human body does not mean they are without value, Frei said. They appear to strongly influence cell signaling pathways and gene expression, with relevance to both cancer and heart disease.

“We can now follow the activity of flavonoids in the body, and one thing that is clear is that the body sees them as foreign compounds and is trying to get rid of them,” Frei said. “But this process of gearing up to get rid of unwanted compounds is inducing so-called Phase II enzymes that also help eliminate mutagens and carcinogens, and therefore may be of value in cancer prevention.

“Flavonoids could also induce mechanisms that help kill cancer cells and inhibit tumor invasion,” Frei added.

It also appears that flavonoids increase the activation of existing nitric oxide synthase, which has the effect of keeping blood vessels healthy and relaxed, preventing inflammation, and lowering blood pressure – all key goals in prevention of heart disease.

Both of these protective mechanisms could be long-lasting compared to antioxidants, which are more readily used up during their free radical scavenging activity and require constant replenishment through diet, scientists say.

However, Frei said, it’s also true that such mechanisms require only relatively small amounts of flavonoids to trigger them – conceptually, it’s a little like a vaccine in which only a very small amount of an offending substance is required to trigger a much larger metabolic response. Because of this, there would be no benefit – and possibly some risk – to taking dietary supplements that might inject large amounts of substances the body essentially sees as undesirable foreign compounds.

Numerous studies in the United States and Europe have documented a relationship between adequate dietary intake of flavonoid-rich foods, mostly fruits and vegetables, and protection against heart disease, cancer and neurodegenerative disease, Frei said. Studies force new view on biology of flavonoids

I don’t mean to sound smug (actually I do), but I was saying this a year ago based on what I had learned about chemical detoxification: polyphenols are the emperor’s new clothes in terms of antioxidant capacity, and that the body wants to get rid of them as fast as it can!

Now that the antioxidant theory is falling apart, researchers are trying to justify the last ten year’s worth of bad advice (eat lots of fruit and vegetables for the antioxidants), by trying to find more complex reasons to self-fulfill their dubious hypothesis that vegetables “are good for you”.

The first assertion is that they increase the antioxidant capacity of the blood by increasing uric acid levels. High uric acid levels are how you give yourself gout – people with gout have inefficient enzymes that causes uric acid to build up in the blood and crystalise in the joints, particularly the toe and finger joints.

In humans, about half of the total antioxidant capacity of plasma comes from uric acid. This is a particular adaption of higher primates, who have lost their uricase enzyme in response to having previously lost their vitamin C enzyme. Uric acid.

There is however, more than one way to skin a cat. Uric acid is formed from purines, heterocyclic aromatic compounds that are formed around a nitrogen base. They have the particularly special quality that they form a part of our DNA and RNA and have biological functions in molecules like ATP and coenzyme A. A diet of red meat and shellfish is high in purines. People who eat meat tend to have higher uric acid levels than people who do not eat meat. Perhaps the most stereotypical way to give yourself gout is to eat a diet of liver and red wine. In other words – why eat vegetables when eating red meat will achieve the same effect of raising your uric acid levels through an inbuilt, natural capacity?

The second assertion is that a diet of fruit and vegetables ‘may help’ induce Phase II detoxification enzymes in the liver. Remember that they have not proven that dietary flavonoids actually help anything overall – they merely have some tenuous population studies that show that people who eat fruit and vegetables as opposed to junk foods (sugar, additives, MSG, trans fats), seem to be healthier. Which they would be, wouldn’t they? If you give one rat a full dose of arsenic, and another rat half a dose of arsenic, the second rat is going to appear to be healthier, isn’t it?

The situation with phase II detox enzymes is actually very complicated. Some specific flavonoids induce certain phase II enzymes through drug-like mechanisms, whilst other specific flavonoids inhibit certain phase II enzymes through other drug-like mechanisms. Flavonoids are not all the same by a long shot, and by randomly eating fruits and vegetables, you are playing the flavonoid lottery. Last year I came across an article that stated the only reason that resveratrol from red wine stayed in the body for any time at all was that some of the other bioflavonoids in red wine totally nuked a bunch of phase I and phase II detox enzymes. In other words, red wine kills the liver.

Beyond this, the only reason you need to induce phase II detox enzymes beyond normal capacity in the first place is because 1) you are up to your liver’s maximum capacity already due to putting so many flavonoids in your system, and 2) you are putting carcinogenic compounds into your system in the first place! Those carcinogens are some of the flavonoids and phenols found in fruits and vegetables! Phenols – found in fruit and vegetables – are one big free radical on a stick.

The last defense of flavonoids comes from the point that they induce nitric oxide synthase. Again, this is a case of very specific flavonoids having this very specific effect, and randomly eating fruit and vegetables is playing a lottery, as some flavonoids (for example soybean flavonoids) have the opposite effect of suppressing nitric oxide synthase. Nitric oxide keeps your arteries wide and flexible. This is all very well for people who have chronically high blood pressure (which can indeed be food chemical induced as well as genetic). But people with fibromyalgia have too much nitric oxide, their blood pressure is usually on the low side, and it’s the excess of nitric oxide that triggers a significant part of the spiralling feedback loop of inflammation, exhaustion and ill health. Considering how many people with fibromyalgia that I know who eat lots of ‘healthy’ fruit and vegetables, it’s hardly surprising…

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Written by alienrobotgirl

25 September, 2007 at 11:13 am

One Response

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  1. […] Flavonoids are also antioxidants and are proclaimed to be useful in fighting cancer. However, […] isn’t so impressed, arguing that the two substances aren’t all they’re cracked up […]


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