Antioxidants - Health Miracle or Profitable Hype? By Stephen and Gina Antczak, authors of Cosmetics Unmasked

Without a doubt, antioxidants are the miracle discovery of the twentieth century - or that's what the makers of dietary supplements and cosmetics would like us to believe. They seduce us with scientific words that we don't understand like 'plant polyphenols' and 'free-radical scavengers' and they promise us these 'natural herbal extracts' will keep our skin young-looking and wrinkle-free; they will keep us fit and healthy; they will protect us from heart disease and cancer; and they can even make us live up to 60% longer. It all sounds wonderful and we are told that these facts are backed up by ground-breaking scientific research. Even well known doctors writing in their Sunday newspaper columns expound on the benefits of antioxidants. But how much of it true?

Oxidation, we are told, is a destructive process that generates free radicals which play havoc with almost everything they touch. They cause the garden hose to crack in the sunshine, they dull paint and cause it to crumble and flake away, they fade the colour of our wallpaper and fabrics, and they degrade the collagen in our skin, accelerating the onset of wrinkles and old age.

The free radicals have been likened to fires burning within our cells, causing damage that could eventually lead to heart disease and cancer. We are told that natural plant polyphenols are free radical scavengers that prevent the build up of free radicals and protect us from the aging process. The French, it seems, have been reaping the benefits of polyphenol antioxidants for countless years. Red wine is rich in polyphenols and there are significantly lower rates of certain cancers and cardiovascular disease in France than in Britain or the USA, where the lifestyles and diets are generally similar. Other populations such as in China and Japan, also have reduced incidences of these diseases. Here it is attributed to green tea which is also a rich source of natural antioxidants.

Public enthusiasm for these ideas has caused a boom in the sales of dietary supplements and cosmetics manufacturers have eagerly jumped on the bandwagon, filling their potions with plant polyphenols and the antioxidant vitamins, E and C. But is there any real science behind the hype or is it all just a profitable fad that is preying on our fears and scientific ignorance?

In this article we intend to look at the scientific facts to see how much we really know about antioxidants. We have simplified some of the scientific ideas and words, and we have put hyphens into long words to make them easier to read. We don't have a problem with this because the article is about antioxidants and polyphenols, and neither of these words are correct scientific terms. But before we blind you with science, let's find out how much you already know about antioxidants with a quick True/False quiz.

1 Vitamin C is the strongest antioxidant normally in our diet; True or False?

2 According to chemistry textbooks, there are no such things as bioflavonoids; True or False?

3 Collagen is the flexible protein found in our skin. As we age the quality and the quantity of collagen in our skin diminishes; True or False?

4 Scurvy is a disease where inferior collagen is produced by the body. This is caused by lack of vitamin C which is essential for the production of healthy collagen; True or False?

5 Pure vitamin C cannot cure scurvy; True or False?

6 The daily requirement for vitamin C is 30 milligrams. Megadoses of vitamin C (doses of 1000 milligrams or more) are probably harmful and have been shown to cause genetic damage; True or False?

7 During the production of healthy collagen, proteins must be oxidised. This involves free radicals, without which the proteins cannot be oxidised correctly; True or False?

8 The bioavailability of polyphenols in our diet is probably zero, in other words, virtually none of the polphenols in our diet will ever get to the cells that produce collagen in our skin; True or False?

9 Polyphenols in cosmetics are unlikely to penetrate the skin and will have little effect on the skin. Those polyphenols that are readily available to cosmetics manufacturers and are known to have an effect on the skin, such as catechol and pyrogallol, have been banned from cosmetics sold within the European Union (EU); True or False?

10 Co-enzyme Q10 (ubiquinone) is said to be an important antioxidant and it has become a popular cosmetic ingredient and health supplement but in fact, its main function in the body is the exact opposite of an antioxidant; True or False?

Of course, the answer to all of these questions is True! If you answered them all correctly without guessing, you probably don't need to read the rest of this article - but you'll be missing an eye-opener.

Now for some science

In a nutshell, contrary to what you hear on TV or read on product labels, oxidation is not always bad and is, in fact, vital for the formation of healthy collagen. And even if polyphenols could get to the right place in the body, which is doubtful, there is no good scientific evidence to show that they can prevent free radicals from doing any damage within a living organism.

A little bit of history

Scurvy is a dietary-deficiency disease caused by a lack of fresh fruit and vegetables in the diet. These provide a host of nutrients, including vitamin C. Without vitamin C and a combination of other nutrients, collagen, the most common protein in our body, is not formed correctly. Small blood vessels become weak and bleed into all parts of the body. This is most noticeable in the skin where widespread bruising appears and trivial wounds are slow to heal. Blood can also leak into the joints, causing severe pain, and the gums bleed, resulting in loosened teeth. In other parts of the body haemorrhages can occur leading to anaemia or more serious, and possibly fatal conditions, depending on where the bleeding takes place.

Today, scurvy is a relatively rare disease but it was common in sailors before the eighteenth century. During their months at sea they had little access to fresh fruit and vegetables but in about 1750, James Lind, a British naval surgeon, discovered that a daily ration of lime juice would both prevent and cure this disease. Limes were chosen because they could easily stored without too much deterioration. (Thus the British became known as Limeys.)

Nearly two centuries later in 1933, Albert von Szent-Györgi, a Hungarian scientist, isolated vitamin C (ascorbic acid) and demonstrated its role in the prevention of scurvy. In some of his experiments he fed guinea pigs a poor diet until they developed scurvy-like symptoms. He then showed that a combination of vitamin C and extracts from the peel of citrus fruits and peppers could quickly restore the guinea pigs to full health, but pure vitamin C administered on its own, could not.

There was an immediate surge in scientific interest to find the mystery factors in citrus peel and peppers that worked with vitamin C to cure scurvy, and today, this research is still in full swing. Many thousands of scientific papers have been written on this subject but despite all this effort, we are still not sure what these mystery factors are. Polyphenols are the front-runners for this but there is still no clear scientific proof that they are. In fact, there is fair amount of evidence that says they are unlikely candidates for the mystery factor prize, but much more on this later.

What are polyphenols?

Polyphenols (pronounced polly-fee-nolls) should more correctly be called polyhydric phenols. They occur naturally in all plants and come in a huge variety of shapes and sizes. They all have two things in common; firstly, they are usually brightly coloured and are used by plants to colour their leaves, flowers, berries and bark, and secondly, they all contain at least one chemical structure called a polyhydric phenol which is very easily oxidised. It is this ease of oxidation that gives polyphenols their antioxidant properties, but more about this later.

Plant polyphenols include the tannins which are found in many leaves and especially the bark of oak trees and in gallnuts; the anthocyanins, anthocyanidins and oligomeric pro-cyanidins which are the brightly coloured pigments in petals, fruits and berries; the flavonoids which include the flavones and the flavan-3-ols, again found in leaves, fruits and berries; and the theaflavins found in green and black tea leaves.

All these words seem almost unpronounceable but a good marketing team can have a field day with them using expressions like, "New antioxidant formula with natural pro-cyanidins to rejuvenate your skin and visibly reduce fine lines and wrinkles." No one understands a word of it but it sounds good and very scientific. The bottom line is, if it sells cosmetics, then use it. And if the words sound too much like vestigial organs that are removed along with your tonsils during childhood, they simply make up a new one that sounds better, hence flavonoids become bioflavonoids and polyphenols are mispronounced pol-if-an-ols. Presumably, if they wanted to market chocolate they would make up the word biochocolate if they thought this would boost sales (especially since it has a more healthy ring to it).

So what does all this have to do with collagen?

The collagens are a family of fibrous proteins that make up a quarter of all the proteins in your body. They are found in skin, muscle, tendons, ligaments, bone, cornea, eye-fluids, internal organs, blood vessels - just about everywhere, in fact.

All of the different types of collagen have a similar chemical structure and are formed in a similar way. They start their lives as single strands of proteins called alpha-chains. Three of these chains line up and spiral around each other in the same way that three cords can be wound together to make a rope. The collagen-rope (which is called a triple helix) forms the tough fibres which are responsible for the strength of muscles and the elasticity of skin.

These alpha-chains want to spiral together in such a symmetrical way because they have a remarkably regular structure. The alpha-chains, like all human proteins, are made from about twenty different smaller molecules called amino acids. Many hundreds of these amino acids thread together like beads on a necklace. The amino acid-beads can be threaded together in any order allowing billions of different combinations of amino acids so a countless range of different proteins can be made.

Collagen is rich in three particular amino acids called glycine, proline and hydroxy-proline. Every third amino acid in the alpha-chains is glycine. Any two of the twenty possible amino acids can go in between the glycine units but they are quite often proline and hydroxy-proline. The hydroxy-proline is essential. It acts like protein-Velcro which holds the three alpha-chains in their regular spiral structure.

This is where the antioxidants come in. While the alpha-chains are being formed, some of the proline units must be oxidised to hydroxy-proline. This oxidation is vital for the formation of healthy collagen. The oxidation process takes place in several steps. Early in the process oxygen, in the form of a free radical, joins onto the proline unit. (Surely not! We've always been told that oxidation and free radicals destroy proteins, not that they build healthy ones, we hear you say.) The formation of this free radical and its subsequent conversion to hydroxy-proline involves an enzyme called a dioxygenase, which has an iron atom at its heart. Just like in all iron compounds, the iron in this enzyme can be in one of two forms called iron(II) (pronounced iron two from the Roman numerals) and iron(III) (iron three). (The old names for these forms of iron are ferrous iron and ferric iron. These went out of use nearly forty years ago so you should be a little suspicious of people who still use them. Their chemistry is a little out of date.)

The dioxygenase enzyme is only useful if it contains iron(II). The iron(II) helps the proline-oxygen free radical change and eventually form hydroxy-proline. During this change, the iron(II) in the enzyme is changed to iron(III) and the enzyme is now completely useless. It cannot be used again until the iron(III) is changed back to iron(II). An antioxidant is needed for this and vitamin C is ideal for the job but it is possible that other antioxidants could also be used.

Vitamin C converts the useless iron(III) in the enzyme back to the iron(II) state and the enzyme can now make some more hydroxy-proline. Unfortunately the vitamin C becomes oxidised and useless, so the body needs a regular supply of fresh vitamin C in the diet. A lack of vitamin C means the enzymes cannot be 'recharged' and inferior collagen is formed with too little hydroxy-proline to 'Velcro' the alpha-chains together firmly. The collagen rope becomes loose and frayed forming weak collagen which is the primary cause of the symptoms of scurvy.

Can polyphenols recharge the iron-enzyme?

In theory, yes they can but they are all inferior to vitamin C. The correct name for an antioxidant is a reducing agent. To a chemist, reduction is the opposite of oxidation. The word, antioxidant, is seldom, if ever, seen in a chemistry textbook. Vitamin C and all polyphenols are reducing agents and their reducing power can be measured. These measurements show that all plant polyphenols are much weaker reducing agents than vitamin C. This means that vitamin C will be much more effective at recharging the iron-enzyme than any polyphenol. It also means that the polyphenols will not be able to 'repair' the vitamin C once it has done its job. Does this mean that polyphenols are not the mystery factors that work with vitamin C? We still don't know.

What do we know about polyphenols in the body?

A glass of full bodied, young, red wine contains about 500 milligrams of polyphenols. As the wine matures, it often throws down a sediment which is rich in tannins and the amount of polyphenols left in the wine is much reduced. When you drink red wine, your mouth feels dry. This is because the polyphenols in the wine cling tightly to proline-rich proteins (PRPs) in your saliva. These PRPs normally act as a lubricant to keep your mouth moist and to help you to swallow. The polyphenols effectively deactivate the lubricating properties of the PRPs and your mouth puckers and feels dry.

The polyphenols in black or green tea, taken without milk, have the same drying effect. When milk is added to tea, the polyphenols cling to the milk proteins so when you drink it, the polyphenols are not available to deactivate your saliva PRPs, and your mouth stays moist. It is reasonable to assume that any polyphenols that get past your mouth will cling to proteins in your digestive system and any that are absorbed into the bloodstream will cling to blood proteins. Between 6 to 8 percent of you blood consists of protein, mainly globulins, albumins and fibrinogen. Any polyphenols that find their way into the bloodstream are likely to cling tightly to these.

Can the polyphenols separate themselves from proteins and get to the right parts of the body to do some good? The answer is no and yes. We know that polyphenols remain tightly attached to PRPs and other proteins within the digestive system. These are not available to the body so we say their bioavailability is zero. Recent experiments on polyphenols attached to blood proteins showed that a powerful solvent called dimethyl sulphoxide (DMSO) which is known to be able to separate polyphenols from other substances, was only able to separate a tiny fraction of polyphenols attached to blood proteins. This evidence suggests that polyphenols in our diet stand very little chance of getting to the places where collagen is made.

But they may do some good. Some fatty-proteins called lipoproteins are particularly prone to free radical oxidation. If a polyphenol attaches itself to a lipoprotein it will be in exactly the right place to scavenge the free radicals and protect the protein. Vitamin E working with vitamin C can also protect these lipoproteins.

The next obvious question must be, if polyphenols cannot get to the skin-collagen factories via the bloodstream, can they get there via cosmetics that we rub into our skin? Probably not. Skin is rich in PRPs and the polyphenols will cling to them like superglue and not get through. In fact, tannins are plant polyphenols that are used to tan leather. That is where their name comes from. During the tanning process the tannin-polyphenols cling to the PRPs in the animal hides and there they remain forever. Of course there is no evidence that using polyphenols on your skin will turn it to leather, but there again, these things have only recently been added to our cosmetics and no one knows what the long term effects of using them regularly, will be.

A good scientist should question everything and one question we have not yet asked is, can polyphenols scavenge free radicals inside living cells? The answer is that real scientific evidence for this is sparse. We can do test-tube experiments in the laboratory and apply chemical theories, and come up with schemes that prove polyphenols can scavenge artificially produced free radicals in test-tubes but we are not sure about what they do inside the plant cells where they are made.

Now it is time for some lateral thinking. Why do leaves change colour in the autumn? Leaves contain large amounts of a green pigment called chlorophyll and they also contain colourful polyphenols and other pigments. The high levels of the green pigment usually mask the other colours. Chlorophyll is rich in nitrogen and magnesium. In the autumn the tree breaks down its chlorophyll and absorbs the nitrogen and magnesium, which is then stored in its trunk over winter, ready to be used next year. As the levels of green pigment falls, the other colours show through in a blaze of autumn colour.

The sun's energy is normally absorbed by the chlorophyll and used to produce food for the plant. When the levels of chlorophyll fall, the sunlight can potentially produce free radicals in the leaves that would damage them and cause them to drop before the tree has a chance to reabsorb the essential nutrients. Recent research at the University of Aukland suggests that the colourful polyphenols and other pigments protect the leaves by absorbing the ultraviolet rays before they can produce free radicals. This suggests that the main role of plant polyphenols is not to scavenge free radicals but to prevent them from forming in the first place. Does this mean that polyphenols cannot scavenge free radicals inside the human body? No, it simply means we have no evidence that they can.

So what is the mystery factor that works with vitamin C?

We don't really know but the next section examins the history of the so called, vitamin P, which we now know does not exist. It is possible, although unlikely, that polyphenols are involved with vitamin C in collagen formation and there is some evidence to suggest that vitamin E, another antioxidant vitamin, could be involved. Minerals like selenium have also been suggested but the long and the short of it is, we simply don't know.

And if we don't know, why do the supplement sellers sound so sure of themselves? They seem to be able to quote scientific paper after scientific paper to prove their claims. But is it good science? In August 2001 the UK Advertising Standards Authority (ASA) told a manufacturer of a health supplement to withdraw their advertisement. The advert claimed that their product contained a combination of eighteen antioxidants, vitamins and minerals that would combat the aging process. They submitted 171 scientific papers and documents to the ASA in support of their claims but the ASA rejected all of them. It seems that much of the science is not good science or it is insufficiently conclusive for anyone to say positively that plant polyphenols actually do any good.

So why does all that red wine make the French healthier? The French themselves laugh at the antioxidant theory. They put it down to good food and good sex in combination with good wine, all contributing to a national sense of wellbeing. The moral being, stop worrying about your health and have some fun. Forget the bioflavonoid pills and pro-retinol face creams, and spend your money on a bottle of red wine instead.

So if this is all rubbish, where do these ideas about bioflavonoids and antioxidants come from?

To answer this question we have to go back to the discovery of vitamin C and the hunt for the elusive vitamin P, also known as bioflavonoid. In fact, the word, bioflavonoid, has no well defined meaning and no agreed common usage amongst scientists or health supplement manufacturers. It is often used interchangeably with the words flavonoid, citrin and a host of other chemical curiosities that occur in plants, and it has even been used as the chemical name of vitamin P. If scientists were to interpret chemical names in different ways we would have a sure recipe for disaster. Imagine what could happen if a prescription for "Co-proxamol" meant different things to different pharmacists.

It is for precisely this reason that the International Union of Pure and Applied Chemistry (IUPAC) set up a system for naming chemicals to ensure that there would be no ambiguous chemical names and no confusion over their meaning. As far as we are aware, bioflavonoid is not part of the IUPAC naming system and we have never seen this word in any text book on advanced organic chemistry. In fact the word "flavonoid" is quite rare in these books, the favoured system being to name each compound individually using the IUPAC system or by using well established, unambiguous trivial names such as "eugenol". We can conclude from this that these fancy sounding words are only favoured by people who want to sell somthing.

As far as we can tell, "bioflavonoid" first appeared at the height of the race to patent the elusive vitamin P. You will recall that Albert Szent-Györgi isolated vitamin C in 1933 and by 1936 he had demonstrated that it could not treat the symptoms of scurvy in its pure form. When mixed with an extract of lemon peel, which was a mixture of natural chemicals he called citrin, vitamin C's therapeutic activity sometimes returned, but not always. He assumed that citrin contained another vitamin which he called vitamin P, and he assumed that this new vitamin was essential for the correct absorption of vitamin C. But vitamin P never achieved true vitamin status because no one was able to demonstrate that a lack of this substance caused a deficiency disease. The word 'vitaminoid' was coined to describe its vitamin-like action but this word seemed to disappear by the late sixties.

Another problem with Szent-Györgi's work on citrin was that his experiments were not reliably repeatable. Some samples of citrin worked and some didn't. This meant that some samples of citrin contained vitamin P and some didn't, presumably because the fruits from which citrin was extracted were in a different state of ripeness with a different chemical make up. The race was now on to separate citrin into its component parts in order to isolate and patent vitamin P.

The first attempts to separate and classify these chemicals was based on colour. A separation process called paper chromatography showed that two families of chemicals were present, yellow compounds which were named flavonoids from the Latin word "flavus" which means yellow, and red compounds which were called anthocyanidins. These compounds were found in all citrus fruits and in many other plants as well. New words, such as citroflavonoids, were quickly coined to increase the number of patents and to maximise profits. But it was soon demonstrated that the flavonoids and anthocyanidins were not bioavailable and could not have any therapeutic effect. (Remember, bioavailable means you can absorb it into your bloodstream by eating it.) But since some citrin extracts worked it was assumed that there must be a bioavailable flavonoid in those extracts. The word bioflavonoid was probably coined to describe the bioavailable flavonoids.

Much poor science was done to prove the existence of bioavailable flavonoids and in 1944, Lavollay published results that proved red wine had a vitamin P effect. He claimed that 2 to 3 millilitres of red wine would double the resistance of guinea pigs' blood vessels in just 1 to 2 hours. So far, four biologists have not been able to explain to us exactly what "resistance" means in terms of blood vessels but if the experiment was scaled up to an adult's weight, it would be the equivalent of drinking between half and three quarters of a bottle of wine. That might have a measurable effect on your blood vessels as well and after drinking it you probably wouldn't care what word was used to describe it.

The red wine was fed to the guinea pigs rather than injected so Lavollay concluded that it contained a bioavailable compound, probably vitamin P, which had a major effect on vascular protection. This opened the floodgates for patent applications for plant extract-based cardiovascular drugs. Incidentally, most of this work was done in the USA because it was the only country that would allow patents on everything from plants and spring water to human genes and breeds of cats. It is also worth commenting here that many of the patented extracts were obtained from the waste generated by other industries such as the peel left over from the orange juice industry, the seeds and skins from grapes from the wine industry, peanut skins and the bark of trees from the timber industry to name but four.

Lavollay decided that the active ingredient in his wine experiments was a colourless compound called catechin. This had been overlooked in the original classification because it was invisible on the paper chromatography experiments. Catechin was chemically similar to flavonoids and is now known as a flavan-3-ol, despite it being colourless. A new word was coined for the flavanols - you guessed it - bioflavanols (which is sometimes spelt, bioflavonols).

The demise of vitamin P

In 1947 Jack Masquelier, a colleague of Lavollay, told Szent-Györgi that there was no such thing as vitamin P in citrin and that "no one in the US believed in bioflavonoids any more." In 1950 he announced that catechin was not the active compound but only a component of the elusive vitamin C co-factor. He decided that the active compounds were formed when two or three catechin molecules joined together. He called these compounds oligomeric pro-anthocyanidins (OPCs) and declared them to be fully bioavailable and the true co-factor that worked with vitamin C to treat scurvy. Between 1948 and 1951 he had registered several patents in the USA for various plant extracts that contained his OPCs and he made many claims about their beneficial effects on the cardiovascular system.

Between the late thirties and the late sixties there were many patented health supplements and prescribed licensed drugs based on flavonoids and anthocyanidins which were widely used to treat a host of cardiovascular diseases. In 1968 the FDA declared that these substances, including citrin, citrus flavonoids, citroflavonoids and bioflavonoids were barely active, if not completely inactive in humans and did not warrant the description of vitamin or health supplement and they also proposed to revoke the licences for their use as drugs.

A new angle was needed if these extracts were to remain profitable and Masquelier was up to the challenge. He carried out numerous in-vitro experiments that showed OPCs were antioxidants and free radical scavengers and quickly assumed that they would have the same action when taken orally, although we have seen no experimental data that would make this a valid assumption. Now that he was no longer claiming to have found the vitamin C co-factor, in 1987 he was granted US patent number 4698360, the first patented free radical scavenging antioxidant plant extract.

A miracle drug is discovered - the anti-aging vitamin.

Masquelier claimed that his new discovery could treat cerebral involution, hypoxia following atherosclerosis, cardiac and cerebral infarction, tumour promotion, inflammation, ischaemia, alteration of the synovial fluids, collagen degradation, sun-damaged skin, cataracts, etc., etc., etc. He should have stopped here but he later went on to claim that his OPCs would prevent aging, hence it would cure "an almost full spectrum of diseases". In fact he called his discovery the anti-aging vitamin.

From our point of view it seems quite remarkable that before the free radical scavenging antioxidant behaviour was observed OPCs were merely able to increase cardiovascular health, a claim disputed by the FDA, but after this observation exactly the same extracts can now cure everything. Others have latched onto this bandwagon and all of the flavonoids, bioflavonoids, citroflavonoids, bioflavanols, and so on, have rocketed back into fashion. Not only can they do all of the above but they are claimed to have antibacterial effects and can also prevent bruising, increase athletic power, prevent fluid accumulation (swollen legs), prevent night cramps, relieve pain, treat oral herpes, promote circulation, stimulate bile production,... and the list goes on ad nauseam. The labels and advertising materials for some of these health supplement still tell us that they contain "bioflavonoid", which is "another name for vitamin P".

Our personal conclusion from this brief history of plant extract health supplements is that this entire sector of the health industry is driven by market forces and not by medical science. Simply because they sound scientific and roll off the tongue easily, words and ideas that were abandoned decades ago have been dug up, dusted off and put through the marketing department for a final polish-up before being used to con an unsuspecting public. We don't expect everybody to be completely literate in IUPAC chemical nomenclature but we do expect regulating authorities to step forward and tell the public exactly what these substances can and cannot do. On that point there is a new website at http://www.nelh.nhs.uk/hth/archive.asp It looks at newspaper and magazine articles about medical breakthroughs and health scares, and spells out the exact science behind the articles, and experts state in simple terms whether the conclusions are valid or not. Excellent! We need many more sites like this.

'Cosmetics Unmasked' by Dr Stephen and Gina Antczak, published by Thorsons (HarperCollins) price £9.99.

ISBN 0007105681

Back to the top

© Gina & Steve Antczak, 2001

This page was last updated, 3 January 2002

CosmeticsUnmasked.Com