Vitamin C the King of Antioxidants, 260 years later

Imagine yourself a British Sailor aboard one of the Queen’s ships.  The date: May 1747.  As a part of the sprawling British Navy, you are the most sophisticated fighting force the world has ever known.  You control most of the world’s oceans after breaking up a possible super-state between the Spaniards and the French in the early 18th century War of Spanish Succession.  So vast were the holdings of the Empire that it is was widely said that, “the sun never set on the British Empire”.

British Soldiers had more to worry about than the spanish - Painting by Loutherbourg d. J., Philipp Jakob

British Soldiers had more to worry about than the spanish - Painting by Loutherbourg d. J., Philipp Jakob

For you and your sailor friends though, who are used to being in the line of fire, a killer far more deadly than the French or Spanish still lurked on every ship.  It’s name was scurvy and it killed upwards of 80% of all sailors during some missions.  Today, we know scurvy is simply a deficiency of Vitamin C but back then, the idea of vitamins was unknown.  Luckily, for you though, you’ve just boarded a ship that is about to become part of the first scientific study in recorded human history.

From a Theory, a Cure

Navy physician (and eventual Post-Captain) James Lind had a theory.  He thought acids helped prevent the rotting sensation that made many sailors succumb to scurvy.  His experiment was simple: divide up twelve sick sailors into six groups of two, feeding them all the same diet.  Each group was then told to take a special acidic substance for about a month to test whether or not it helped them (cider, vitriol, vinegar, seawater, lemons/oranges and ‘spicy paste’).  As oranges and lemons were in short supply, that group could only continue with Lind’s requests for 6 days.

The first medical study

The first medical study

But then, after those 6 days, something miraculous happened – both of the sailors eating the oranges/lemons recovered, one fully and one partially.  Meanwhile, all other groups continued in illness.

Even though Lind was mostly unaware of what he had discovered (he still considered the acidic properties of the oranges/lemons to be the curative ones), this was the first recorded medical benefit derived from Vitamin C.  It took another 50 years but by 1795, another pioneering Navy physician named Sir Gilbert Blane helped make lime juice mandatory on every navy ship, giving rise to nickname ‘Limeys’.  Really, the men were ‘VitaminC-eys’, just scratching the surface of what Vitamin C could do.

Vitamin C’s Evolutionary Role

Quite a bit more time would pass before Vitamin C earned its name though (a Hungarian by the name of Albert Szent-Györgyi won a Nobel Prize for the work in 1937).  But more than any man, Linus Pauling – the decorated physicist, brought Vitamin C into the American vernacular as the powerful antioxidant everyone needed to consume in large amounts.

Linus Pauling

Linus Pauling

Exactly what amounts was the focus of Pauling’s late life work.  He saw Vitamin C not so much as supplement but a requirement for human health. This idea stemmed from the evolutionary basis of mammals.  As our distant ancestry crawled out of the oceans, they found themselves desperately short of antioxidants.  The ocean, filled with the powerful antioxidant iodine, provided sea life abundant protection against oxidative stress.   But on land, iodine is in extremely short supply – hence the evolutionary dilemma.  How did these early creatures of the land survive?

In short, Vitamin C.  Early terrestrial life eventually developed the ability to synthesize Vitamin C inside their own bodies, creating a ready store of potent antioxidants whenever stressful events would occur.  Most mammals on planet earth still possess this magical power, with one very notable exception – humans.

Exactly why we lost this seemingly essential evolutionary advantage is unknown but Dr. Pauling’s advice was to supplement the body so heavily with Vitamin C that you might as well be producing it internally.  He reportedly took upwards of 10 GRAMS of Vitamin C per day – 167X as much as the USDA RDA’s 60mg/day recommendation.  It should also be noted he lived into his late 80s, an interesting correlation if nothing else.

Off The Rails

Pauling’s devotion to Vitamin C was, at times, religious.  He wrote books about it and was fiercely defensive about the vitamin.  Websites around the internet call his devotion to orthomolecular medicine – the right molecule at the right time – as quackery.  That may be an over-stretch but medical studies severely question the logic.

Meta-review of antioxidant vitamin supplementation find they actually increase mortality rather than reduce it [1], although vitamin C is given a neutral rating.  Other very large-scale studies show Vitamin C only mildly reduced cold symptoms in non-athletes [2, 3], and proved ineffective against cancer [4] regardless of the stage of the cancer [5] – one of Pauling’s cardinal claims.    The evidence for Vitamin C as a cure-all seems weak at best.

Still, no study can debate Vitamin C’s antioxidant power and inside of the human body it remains unmatched (although a new market full of many who now try to sell you other more powerful antioxidants at staggering prices has sprung up).

Antioxidant Craze, Reinventing the Wheel

We are in the midst of another post-Vitamin C antioxidant explosion, mostly thanks to the idea of inflammation.  Public knowledge of the connection between chronic disease and inflammation has become common, and upwards of 60% of the public see antioxidants as the answer to the problem [6].

Organic Goji Juice - think its going to save your life?  Think again

Organic Goji Juice - think its going to save your life? Think again

The correlation seems an easy one to understand: if inflammation causes most disease, get rid of it with antioxidants.  Such simplicity has fueled a health craze over the last decade around the idea.  Pomegranate juice companies, cereals with green tea extract, $40 bottles of goji juice and most recently the Oprah-fueled acai berry situation illustrate this point all too well.  But, behind the sales pitches, it turns out the relationship between oxidation and inflammation is not so convenient.

Green tea, berries, rose hips and all the others do contain massive amounts of antioxidant activity but only in a laboratory setting.  See, most of the claims these ‘antioxidant powerhouse’ type products make rely heavily on studies that show these foods preventing oxidative stress in a test tube, not in real life.  In fact, whenever miracle foods like goji berries are closely examined, they consistently show just how little antioxidant activity they actually generate in the body.

And that’s where the Linus Pauling Institute comes into play.  A scientific powerhouse focused on studying the science behind micronutrients, the Institute produces a semi-annual newsletter simply called ‘The Research Newsletter’ whose latest Summer 2009 edition went into great detail about Vitamin C’s benefits versus now popular flavonoid antioxidants.

Director Balz Frei, Director and Endowed Chair Professor of Biochemistry and Biophysics and one of the lead researchers in the field, had a lot to say about antioxidants.  He describes Vitamin C’s main advantage being the fact the body readily absorbs it at far higher levels than the more potent antioxidants like acai and pomegranate.  So it may be true that there are more potent antioxidants than Vitamin C, they can’t have near the impact because the body will not absorb them.  Here we quote the most interesting part of the Q&A session from that newsletter (emphasis mine -ed).

Q:  Do you agree that flavonoids have strong antioxidant functions?

A: In the test tube, yes, but not in the human body.  In test tube or in vitro experiments, flavonoids do pretty well as antioxidants, especially if one calculates the number of free radicals that each flavonoid molecule can scavenge.  These are large molecules with lots of hydroxyl groups, so it makes sense that they would be able to scavenge a lot of free radicals.  But if you look at their reaction rates, they are not nearly as effective as vitamin C.  Each vitamin C molecule can only scavenge two free radicals, so quantitatively vitamin C might not be as good as flavonoids, but qualitatively it’s much better.

More importantly, in the body flavonoids are not present at nearly the same concentrations as vitamin C because their absorption into blood from the gastrointestinal tract is very limited.  For example, flavonoids may be found [in the blood at extremely low concentrations] whereas vitamin C may be present in concentrations [much higher].  That tiny flavonoids concentration [of flavonoids] cannot make a significant contribution to antioxidant protect.

In cells, the situation is even more extreme – vitamin C is present in cells at a concentration…that’s at least 40 times greater than its [concentration in the bloodstream].  The concentration of flavonoids in the cells is still only [miniscule], and its impossible for them to significantly contribute to free radical scavenging in cells.”

Even with the research showing Vitamin C does little to aid in colds or cancer prevention, Dr. Frei general idea – that Vitamin C works its way deep into the body – would make it a more effective antioxidant inside of the body than any of these newer, expensive health foods.

Latest Research

All is not lost for the antioxidant flavonoids however.  Dr. Frei and his colleagues at the Linus Pauling Institute are a part of the NIH’s Complementary and Alternative Medicine (CAM) research program.  Spread across the world, these research centers are exploring the most advanced theories on micronutrients like flavonoids and radical theories on chronic diseases like cancer.  But compared the financial resources traditional western medicine receives, the NIH CAM programs are quite small and often threatened with suspension of their research dollars by politicians that believe their work is quackery.

You'd probably be better off just eating more oranges...

You'd probably be better off just eating more oranges...

Despite the unfortunate financial situation, enterprising researchers are quickly filling in the gaps about flavonoids – albeit not quickly enough.  There is still no prevailing theory on how flavonoids truly impact the body.  Parts of the puzzle are in view though.  It is well known that certain sweet fruits like apples create a strong reaction by triggering the body’s uric acid antioxidant system.  So, in that way these fruits act as secondary antioxidant triggers, although usually at a much lower potency than Vitamin C.

But a larger, more encompassing theory of how exactly these flavonoids are triggering the body into a more healthy state is still out of reach.  Dr. Frei posits a theory later in the newsletter we quoted above that deserves reprint here, as he addresses how he thinks flavonoids help the body [technical explanation, you've been warned]:

A: As I explained, flavonoids are present in very small concentrations in plasma and cells, so there must be mechanisms that are triggered by these low concentrations.  For example, hormones in the body are also present in very small concentrations.  They react with receptors, which then send out signals inside cells that produce a biological effect, even though you start out with a very small concentration of the effector molecule.  I think the same is true with flavonoids.  They bind to proteins and if the protein happens to be  receptor and triggers a cell-signaling cascade, you may end up with a significant biological effect.

For examples, black tea has a lot of polyphenols or flavonoids called catechins.  They have been shown to activate the estrogen receptor alpha, which then modifies endothelial nitric oxide synthase, increasing the enzyme’s activity to produce nitric oxide (an important antioxidant -ed).  I think that most flavonoids act by increasing cell signaling, activating enzymes, or increasing the activity of transcription factors, leading to upregulation of certain proteins.

The general idea from the Dr. Frei and other researchers is that flavonoids are triggers, flipping important switches in the body that activate other systems, leading to a health effect.  But, exactly what is being flipped or what that ‘cascade’ of flipping really does inside the body is conjecture for now.

The Way Forward

This dichotomy of information seems disparate and complex but there are some themes here for you to take away.  If you really want to prevent cellular oxidation, the song remains the same: Vitamin C is the most important antioxidant nutrient known to man.  The bang-for-the-buck you can get from an inexpensive Vitamin C supplement appears proven many times over -  from study #1 aboard a wooden navy ship in 1747 to the advanced micronutrient labs of 21 century America.  The Linus Pauling Institute recommends 400mg/day from their research.  We covered the conflicting science above which states a mostly neutral role for Vitamin C in chronic disease.

Flavonoids, however, really aren’t what the marketing campaigns have made them out to be – but that doesn’t mean they aren’t important.  A misread of the science and an unassuming public has created a cottage industry for supplement makers and get-rich-quick weight-loss schemes based around exotic berries.  It is clear however, that these flavonoids are triggers for some major responses – even some antioxidant – inside of our bodies.  Adding some organic berries or a nice cup of tea, brimming with flavonoids, is only going to help you but you shouldn’t be paying $50/bottle for some super juice on an infomercial.

Nothing replaces a diet where you finally put down the fried, factory farm chicken-french fry-64oz soda value meal and pick up some whole grains and vegetables.  However adding in some flavonoid-and vitamin C rich fruit to your life presents a significant and inexpensive way to enhance your health.  Way more than 260 years of science back up that claim.


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