Archive for the ‘The Antioxidant Myth’ Category
An interesting quote from a blog I came across about natural pesticides compared to artificial ones. I apologise if someone sent me a link to this, I have no idea where it came from!
Dr. Ames began rethinking this war against synthetic chemicals after thousands of chemicals had been subjected to his test. He noticed that plenty of natural chemicals flunked the Ames test. He and Dr. Gold took a systematic look at the chemicals that had been tested on rodents. They found that about half of natural chemicals tested positive for carcinogencity, the same proportion as the synthetic chemicals. Fruits, vegetables, herbs and spices contained their own pesticides that caused cancer in rodents. The toxins were found in apples, bananas, beets, Brussel sprouts, collard greens, grapes, melons, oranges, parsley, peaches — the list went on and on.
Then Dr. Ames and Dr. Gold estimated the prevalence of these natural pesticides in the typical diet. In a paper published in 2000 in Mutation Research, they conclude:
About 99.9 percent of the chemicals humans ingest are natural. The amounts of synthetic pesticide residues in plant food are insignificant compared to the amount of natural pesticides produced by plants themselves. Of all dietary pesticides that humans eat, 99.99 percent are natural: they are chemicals produced by plants to defend themselves against fungi, insects, and other animal predators.
We have estimated that on average Americans ingest roughly 5,000 to 10,000 different natural pesticides and their breakdown products. Americans eat about 1,500 mg of natural pesticides per person per day, which is about 10,000 times more than the 0.09 mg they consume of synthetic pesticide residues. Synthetic v. Natural Pesticides
It looks like all that evidence of increased lifespan due to calorie/carbohydrate restriction goes down the pan when you start taking antioxidants:
A new study in the October issue of Cell Metabolism, a publication of Cell Press, reveals that worms live to an older age when they are unable to process the simple sugar glucose. Glucose is a primary source of energy for the body and can be found in all major dietary carbohydrates as a component of starches and other forms of sugar, including sucrose (table sugar) and lactose.
“In the US and Europe, added sugar accounts for 15 to 20 percent of daily calories, and the breakdown of that sugar always generates glucose,” said Michael Ristow of the University of Jena in Germany and the German Institute of Human Nutrition Potsdam-Rehbrücke. If the findings in worms hold for humans, it “suggests that, in healthy people, glucose may have negative effects on life span.” The findings may also cast some doubt on the prevailing treatments for type 2 diabetes, all of which are aimed at lowering blood levels of glucose by increasing the amount of sugar taken up by body tissues, Ristow said.
What’s more, Ristow’s group further demonstrated in their report that antioxidants and vitamins given to the worms erased the life-extending benefits of sugar deprivation, raising questions about the widespread use of antioxidant supplements, according to the researchers.
In westernized countries, glucose represents a key dietary component since the most commonly ingested sugar, sucrose, contains equal amounts of glucose and fructose, the researchers noted. Nevertheless, it is a matter of debate whether glucose and other carbohydrates have a relevant effect on disease burden and mortality in humans, they said.
To begin to address the issue in the current study, the researchers exposed the nematode Caenorhabditis elegans to a chemical that blocked the worms’ ability to process glucose, producing a metabolic state the researchers said resembles that of dietary glucose restriction. That treatment extended the worms’ life span up to 20 percent, Ristow reported, noting that the observed gain extrapolated to humans would mean an additional 15 years of life.
Unable to depend on glucose for energy, the long-lived worms ramped up the activity of cellular powerhouses known as mitochondria to fuel their bodies, Ristow said. That mitochondrial activity led to the increased production of reactive oxygen species, sometimes referred to as free radicals. In turn, the worms’ defenses against “oxidative stress” increased, the researchers found.
Free radicals are usually considered harmful, Ristow said, and scientists have generally thought that exposure to them would shorten life span. The new findings suggest that, at least in some cases, the opposite may be true.
Indeed, even when the researchers returned the worms to their normal environment, allowing them to again use glucose for energy, the worms’ increased defenses and longevity persisted, Ristow said. In contrast, treatment with antioxidant vitamins prevented the oxidative stress and the defenses against it, eliminating the life-boosting effects. Ristow called the result “scary” because it means that, rather than being protective, antioxidant pills may actually leave the body more vulnerable by thwarting those natural defenses.
Ristow doesn’t recommend that people toss out their multivitamins just yet, however, cautioning that his findings were made in worms. He also noted that antioxidant-rich foods, including fruits and vegetables, contain thousands of substances—many of which have yet to be identified. While scientists don’t yet know what all those ingredients do, it’s clear that such natural foods support “healthy pathways,” Ristow said. Avoiding sweets may spell a longer life, study in worms suggests
After scientists discover – shock horror – that oxidation is as important as reduction, and the body self-regulates its defences against free radicals, note again the concilliatory “well antioxidants must be good in some way” paragraph concluding this article!
Of course, we are not worms. We have exactly the same mitochondria behaving in the same kind of way, but we’re couldn’t possibly be like worms…
Thanks to Chris again for this article too!
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…
Chris just sent me a great link!
ANTIOXIDANT overload may underlie diseases such as congenital heart failure and Alzheimer’s, a study has shown.
Research on mice suggests that antioxidants, generally seen as beneficial to health, may sometimes do more harm than good.
Vitamins C and E and numerous compounds found in fruit and vegetables act as antioxidants.
They are generally regarded as healthy since they neutralise free radicals which are destructive groups of atoms that damage cells and DNA.
Many serious disorders, ranging from heart disease to cancer, are wholly or partly blamed on free radicals.
But there is another side to the coin – reductive stress, which some experts believe can be triggered by antioxidants.
Reductive stress, paradoxically, causes atoms to gain electrons, thereby acquiring a more negative charge.
The new research confirms that it can have damaging effects, too, and may have been overlooked as a cause of human disease. The Scotsman
I’m not a chemist – I’ve a good grasp of the concepts but what I know about chemistry is self-taught. But the emphasis on oxidative stress as the cause of everything that goes wrong in the body has always struck me as a bit weird and wrong as I’ve stumbled across so many examples of oxidation being beneficial under the right circumstances, for example, the body deliberately creates free radicals to fight off infections. Oxidation is in fact essential to life and a normal bodily process. It also strikes me as pretty interesting that most of the chemicals that make me feel so ill are antioxidants.
There was a paper published on reductive stress in 2002 but unfortunately this isn’t available online. I found a letter agreeing with the paper that is very telling:
We are writing to agree with Dr B Lipinski’s perceptive comments (Lipinski, 2002) and to suggest that they are of wide relevance. In particular, the importance of reductive stress should be more widely recognized. The prevailing view is extraordinarily blinkered. In PubMed (2001) there are 8957 citations to oxidative stress and none to reductive stress. This reflects not reality, but the mistaken but widely held ideas that oxidative stress is common, that it is the main source of biological free radicals, and that it is (or should be) susceptible to correction with antioxidants. In fact, extensive clinical and experimental work over the past 30 years has failed to reveal a single abnormal clinical state which could be confidently ascribed to oxidative stress or, more importantly, which has convincingly benefited from antioxidants. One reason is probably the initial difficulty of grasping the concept of reductive stress: another the relative paucity of experimental methods for demonstrating and measuring it. Evidence in support of a concept of reductive stress: Reply
Sounds like another case of The Emperor’s New Clothes, doesn’t it? I also found this press release:
Science Daily — Antioxidants are widely considered an important defense against heart disease, but University of Utah researchers have found excessive levels of one antioxidant–reduced glutathione–actually may contribute to the disease.
The findings, published in Cell, indicate a new class of drugs can be developed to treat or even prevent heart disease caused by “reductive stress,” according to Ivor J. Benjamin, M.D., Christi T. Smith Chair of Cardiovascular Research, division chief of cardiology at the U School of Medicine and the study’s principal author.
The protein alpha B-Crystallin, termed a molecular chaperone, normally helps long strips of other proteins fold inside cells. When it works properly, the cell produces the correct amount of reduced glutathione, which is healthy for the body. Unfortunately, when the gene that makes alpha B-Crystallin is mutated in humans, the protein unfolds improperly into aggregrates, the hallmark of the condition in different organs, including the heart. When that happens, reduced glutathione is produced in such excessive levels that it harms the heart, Benjamin said. The resulting condition is called reductive stress.
In a study of laboratory mice with failing hearts caused by mutant alpha B-Crystallin, Benjamin and several U of U colleagues found increased activity of the biochemical pathway leading to high levels of reduced glutathione in the animals.
Glutathione, one of the body’s most powerful antioxidants, is regulated at multiple steps principally by the G6PD enzyme. To establish the connection between reduced glutathione and heart failure, Benjamin mated mutant alpha B-Crystallin mice that carried too much G6PD with mice that had far lower levels. The resulting offspring had normal levels of reduced glutathione and did not develop heart failure.
“Lowering the level of reduced glutathione dramatically changed the survival of these mice,” Benjamin said. “Basically, we prevented them from getting heart failure.”
Heart, Alzheimer’s, Parkinson’s, and other deadly diseases are associated with oxidative stress, in which “free radical” molecules are produced in reaction to oxygen intake. Free radicals travel the body, triggering chemical reactions that damage proteins and causing them to form aggregates. Many people take antioxidants to prevent heart and other protein-aggregate diseases, but there actually is scant evidence to prove they work, according to Benjamin.
Until now, reductive stress has not been looked at in the context of disease. “This is a case of too much of a good thing,” Benjamin said. “Our findings indicate reductive stress warrants a more thorough investigation.”
By lowering the levels of reduced glutathione without the altering mutant gene encoding thee alpha B-Crystallin, , the study shows reductive stress can be addressed through new drugs that target the genetic pathway causing the problem, according to Benjamin.
“This field of medicine has not appreciated reductive stress and its influence on disease,” he said. “This is about balance needed in the environment of our cells, and it can have profound consequences on the treatments of heart disease and other serious disorders.” Too Many Vitamins? One Antioxidant Linked To Heart Disease, Study Shows
Which is an interesting take on glutathione, isn’t it?
There are a few flavinoids that I am rather suspicious of, because they are structurally similar to artificial antioxidants that failsafers react to, like the benzoates and gallates, and they are particularly high in foods that have a reputation for causing reactions. If this is so, anyone who reacts to salicylates should also react to these flavinoids, since they act on the same pathways
EGCG, Catechins, natural gallates
– high in broad beans, wine (particularly red, explains a lot!), tea, some berries and stone fruit
– high in capers, kale, dill, broccoli, turnip greens
– high in peppermint and all citrus particularly lemon
– high in all citrus particularly lemon
Possibly some proanthocyanidin oligomers
– high in cinnamon, cocoa, grapes, some berries, some stone fruit, some nuts
As well as being high in kaempferol, broccoli, which has a reputation for being reactive, is very high in total polyphenols compared to most other commonly eaten vegetables, and it also contains some serotonin and free glutamate. I think there might be something of a “cocktail effect” going on that makes it and some other leafy greens more reactive in comparison to other salicylate-containing foods.
It wouldn’t be hard for me to do an EGCG experiment and a hesperetin experiment, since I still have some of those in my vitamin cupboard of wonders. But I’m not in any hurry as I feel very good at the moment.
There are a group of synthetic antioxidants that range from E310-E312 called the gallates, including propyl gallate, octyl gallate and dodecyl gallate. They’re on the “nasty antioxidants” list. They’re based around gallic acid, also known as 3,4,5-trihydroxybenzoic acid – that’s right, they’re closely related to benzoates.
If you paint your skin with benzoates, you will get an instant rash. They’re thought to cause angioedema and urticaria by triggering not histamine but serotonin release.
Gallates reportedly cause the same effects as benzoates. These chemicals are notorious; they cause the full range of health problems like asthma, eczema, and the ADHD behaviour we’re familiar with in food chemical intolerant kids. Failsafe parents describe their children as having screaming fits when they are exposed to unlabelled antioxidants.
I had a small epiphany last night after reading something about green tea that had been posted on FailsafeNT. The chemical name of green tea extract had never struck me before.
Green tea extract is basically catechins, which make up as much as 25% of the dry weight of the tea. I once tried to lose weight on green tea extract, and I felt really run down, irritable and awful the whole time, and I kept recycling the same 2lbs on the scale.
The names of the catechins are: epicatechin, epigallocatechin, and EGCG (epigallocatechin gallate), the most abundant polyphenol of all. That’s right. Green tea is made of gallates. Green tea extract has been portrayed as a source of “wonderful” antioxidants. In actual fact green tea appears to be made up of the richest natural source of nasty antioxidants. Go look at the drawings of EGCG and gallic acid on wikipedia if you don’t believe me. EGCG is just a couple of gallic acid molecules tied together via another molecule, all arms protruding.
EGCG is even marketed as a “fountain of youth” for skin cells because it smoothes out wrinkles. Is this because, like other dodgy anti-wrinkle cosmetics, it’s causing angioedema? It’s marketed as an anti-inflammatory. Is this because it is acting like aspirin to block the all-important arachidonic acid pathway? Obviously if this is the case, it will cause asthmatic and pseudo-allergic reactions.
It’s really no wonder I had such horrible reactions to green tea extract, and in more recent trials, awful arthritis pains when I drink green tea.
Now I don’t care how many times EGCG helps me to recycle the antioxidant value of vitamin E, if it makes run around like a mental case until I fall over and burst into tears, I don’t want it in my body.
I’ve been reading Rob’s Zero Carb Daily blog. He’s one of the carnivores. He has a few interesting things to say. For example, this quote from The Bear (the carnivore’s guru), which I have to reproduce because it greatly amused me:
Green leafy vegetables have little or no nutritive value, and are eaten as “eye food”. In fact some, like celery and lettuce have less caloric value than it takes to process them through your system, like sand. Some, like spinach, contain a toxic blood poison, oxalic acid. This dangerous chemical is so high in rhubarb that the green leaves are capable of causing death. Why eat this rubbish?
I agree that there is only maybe 20 percent of the weight of “leafy greens” which is carbs, but why eat something so toxic and rough? Would you intentionally put a pinch of sand in the crankcase of your car? Older people suffer from malnutrition in spite of “excellent diets” due to the scar tissue in their intestines from a lifetime of exposure to roughage in their food. In the short term it causes the intestines to coat themselves with mucus, which also interferes with absorption of nutrients.
All plants have toxins, chemical defenses against herbivores are much older than the mechanical ones like the spines of cacti. People have struggled for hundreds of years to breed out most of these defenses, which is why you cannot grow them without pesticides.
If you doubt me, eat a cupful of wild lettuce (a very common weed), and see how long you can remain awake. It contains a glucoside, letucin, called “lettuce opium”, which was bred out of the cultivated plant. Zero Carb Daily (Atkins and the Good Carb myth)
Lettuce is one of the very few plants that human beings eat raw, the implication being that it has to be one of the few truly Paleolithic vegetables. But it turns out to be a Neolithic food we’ve cultivated the poisons out of? I’ve maintained for at least a year now the stance that lettuce is pointless. It doesn’t add nutrition or calories. It just adds roughage and poisons. It tastes bad, it has an unpleasant mouth feel, and my life was about 10% better when I gave up forcing myself to eat it.
Rob also has an interesting post about fibre. Now, I have an instinctive aversion to fibre because of what it does to my guts, which is not pleasant. I’ve also had some pretty good nutritional reasons for avoiding it since I read Barry Groves’ Fibre and Colon Cancer article a couple of years ago.
It turns out that the mechanism by which fibre keeps you regular is deeply unpleasant:
If you ever wondered just how a high-fiber diet helps keep you, well, “regular,” scientists may have the answer.
Their results suggest that as these bulky foods make their way down the gastrointestinal tract, they run into cells, tearing them and freeing lubricating mucus within.
More mucus is good, says Dr. Paul L. McNeil, cell biologist at the Medical College of Georgia and corresponding author on the study published online Aug. 21 and scheduled for the September print issue of PloS Biology. “When you eat high-fiber foods, they bang up against the cells lining the gastrointestinal tract, rupturing their outer covering. What we are saying is this banging and tearing increases the level of lubricating mucus. It’s a good thing.” Scientists learn more about how roughage keeps you “regular”
It’s a good thing? Does that mean that the resultant colon cancer caused by all the cell damage is also “a good thing”?
The scientists aren’t certain how many times cells can take a hit, but they suspect turnover is so high because of the constant injury. Potentially caustic substances, such as alcohol and aspirin, can produce so much damage that natural recovery mechanisms can’t keep up. But they doubt a roughage overdose is possible.
This caught my eye. Though intestinal problems including malabsorption syndromes are common amongst the food chemical intolerant, I hadn’t investigated how salicylates (aspirin) might cause this. It seems salicylates simply cause so much cell damage to the colon that the body can’t repair itself fast enough.