Step 4: Antioxidants

The brain runs better when it's clean.

Human bodies are much more complex and interesting ... but to continue our auto analogy if B vitamins are like the spark plugs of the body, trace minerals like the nuts and bolts, if EFAs are like an electrical system, then keeping our bodies in abundant supply of antioxidants is like keeping every part of the car clean. Paint, interior, inside the dashboard, wiring harnesses, light fixtures, inside and outside the engine - all of it, clean.

This article describes why we need antioxidants supplements and how to use them. For a look at the peer-reviewed evidence base on antioxidants and mental health, go here.

Ever notice how much smoother your car runs when it's clean? Don't laugh. Much of the work an engine does is to push the car against wind resistance, especially at speeds over 30 mph. When a car is covered with dirt there's a lot more drag as it moves through the air; washing the car and covering it with wax helps it slip much more easily through the atmosphere and so the engine has less work to do.

Antioxidants keep our bodies running "clean." They work by soaking up free radicals, so first a little chemistry's in order. Atoms are groupings of protons (with a positive charge) and electrons (with a negative one and neutrons (with no charge.) Electrons "orbit" in pathways called shells around their proton/neutron nuclei. It's in the nature of atoms to have either one or two electrons in their outer shells; two electrons in the shell makes for a stable configuration, but having only one electron in the outer shell makes the atom very electrochemically active. That half-filled outer shell wants another electron to make it balanced and stable. This is the force that leads to molecules ... when two atoms with half-filled outer shells find each other they join forces and create a bond.

Hook up a few or a few dozen or dozens of atoms in this way and preto - a molecule. The balance of electrical forces between atoms gives the molecule a characteristic shape; and it's this shape which gives it its chemical properties. How much temperature is required to melt a bunch of these molecules, what color they are, how something behaves ... all flow from the shape and size of the molecules that make it up, their number and the balance of electrical forces holding them together.

Free radicals are tiny molecular thieves. They're highly reactive molecules with an unbalanced outer shell; this means that they're quick and ready to steal electrons from other, larger, more electrically balanced molecules wherever free radicals find them.

Now what makes those larger molecules useful, useless or toxic to the body is their shape. And what gives them their shape is the balance of electrical charges. Throw a bunch of electrochemically larcenous free radicals into an organic structure and they start grabbing electrons willy-nilly from the outer orbitals of the atoms making up that complex organic structure. Things go downhill fast. This process is called oxidation, though this is not the useful, energy-generating kind of oxidation that goes on in the mitochondrial energy-factories of the cells. This oxidation is more like the kind of oxidation that happens to the paint of a car that gets parked in the backyard for ten years or the skin of a chain smoker.

A similar thing happens to vegetable oils, especially when they're heated. Hot oils exposed to air oxidize, and this oxidation itself creates more free radicals. As we've seen, oxidation in organic fluids frequently becomes a chain reaction in which one oxidized molecule becomes a free radical itself and goes on to oxidize still more molecules. In a solid oil-containing food this process is visible in a piece of cheese left out overnight on the counter. The discolored, slightly shrunken, cracked edges and surface of the cheese have oxidized. In common language we speak of the same process and something becoming spoiled, rotted, rancid.

Our bodies generate large amounts of free radicals all the time as they are produced by the energy-generating oxidizing processes going on in each cell at every moment. Immune cells digest their targets by generating large amounts of free radicals which then destroy the offending microbes (or other substances) by stealing so many electrons from their organic molecules that their structures dissolve. Sort of like being sandblasted to death. We call this process inflammation.

We also absorb free radicals from air pollution, cigarette or exhaust smoke, and rancid fats and oils in our food. Food that's fried in oil that's exposed to air and not changed frequently can be heavy in free radicals.

In the normal course of things the body soaks up these free radicals, protecting itself by generating antioxidant molecules either internally or by consuming them by mouth. But sometimes things get out of control, particularly after toxic exposures or during infections or auto-immune conditions, and it's smart to get help.

Antioxidants work by being more electrochemically attractive to free radicals than are the body's own organic molecules in cells and tissues. There are literally tens of thousands of different antioxidants. Vitamins C and E and A are three of the best known; there's also super-oxide dismutase (SOD, which migrates to joints), beta-carotene (which the liver converts to vitamin A but which is a potent anti-oxidant in its own right), Co-Q10 (which in another role is an important part of the energy-generating Krebs cycle) and alpha-lipoic acid (which has a special anti-aging role in that it protects mitochondrial DNA, making it very useful for diabetics.) There are also thousands upon thousands of other antioxidants grouped into two large classes: the water-soluble bioflavonoids, chemically related to vitamin C, and carotenoids, related to vitamin A. Selenium is an anti-oxidant mineral which appears to play a role in cancer prevention.1,2

Bioflavonoids and carotenoids are found in abundance in brightly colored fruits and vegetables. Vitamin C is found in abundance in the inside, soft white part of citrus fruit peels, the cortex (not the peel itself, which contains toxic turpenes.) Dark green leafy vegetables like chard, collard greens or cale are also rich natural sources of vitamin C.

When most antioxidant molecules absorb a free radical they're generally out of action for awhile. Vitamin C plays a particularly special role here as it's such a powerful antioxidant that it can accept free radicals from other antioxidant molecules, recharging them. If one thinks of all the other antioxidants as beat cops, out on the street collaring common criminals, then vitamin C is the jail - once a beat-cop antioxidant transfers its free radical prisoner to a vitamin C hoosegow, it's capable of going back out into the molecular arnachy and collaring more corrosive free radicals.

Most mammals can make large amounts of vitamin C in their own bodies, interconverting it with blood sugar (blood sugar becomes vitamin C and vice versa, as needed.) A few higher primates (including us) and guinea pigs are the only mammals that can't. Our ancestors were apparently living in an environment rich enough in vitamin C containing fruits and vegetables that roughly 40 million years ago our bodies lost interest in going to the trouble of making it themselves.

Linus Pauling, the two-time Nobel prize winner, gained notoriety a couple of generations ago by investigating this at some length. He measured the amount of vitamin C generated by a number of different mammalian species, averaged the amounts across species and then calculated how much vitamin C humans would produce if this amount was adjusted to an average human weight of about 170 lbs. He determined that if we were making as much vitamin C per pound of body weight as the average mammal we'd be generating about 17,000 mg/day.

The fact that in most mammalian bodies large amounts of vitamin C are generated from blood sugar means that sugar and vitamin C share the same cellular transport mechanisms. And this means that consuming substantial quantities of sugar can block the body's utilization of vitamin C, a prospect that should give pause to anyone considering the use of "chewable" vitamin C products containing large amounts of sugar.

There's a dynamic in chemistry whereby when the end-product waste of a chemical reaction builds up in the vicinity of the reaction itself it tends to inhibit and ultimately shut down the reaction. Light a candle flame inside of a glass cup and cover the cup; soon the flame will go out as carbon dioxide builds up inside the cup. Carbon dioxide is a byproduct of combustion; as it builds up it inhibits the flame until ultimately there's so much CO2 the reaction can't proceed.

Linus Pauling observed that human immune systems need vitamin C to function. Remember that immune cells attack their targets by generating large amounts of corrosive free radicals. Sinc vitamin C soaks up these free radicals Dr. Pauling reasoned that if large amounts of vitamin C were taken when the body was fighting off an infection the immune system would be able to operate at its peak design efficiency.

When a mammalian body has absorbed enough vitamin C it gets diarrhea. This is called taking vitamin C to bowel tolerance. Dr. Pauling also observed that if a mammal was actively fighting off an infection its bowel tolerance would increase, sometimes by a very large factor. Humans, for example, usually hit their bowel tolerance for vitamin C somewhere in the neighborhood of 6-7,000 mg. But if a human is fighting off a cold or other infection they can sometimes take 15, 20 or in acute situations even 30 gms before getting diarrhea. Dr. Pauling thought that this showed that taking large amounts of vitamin C was sometimes justified; he concluded that if we want our immune systems to function at peak capacity we should ideally consume enough to be within about 5% of our bowel tolerance.

This idea didn't go over very well with the medical scientists of his day (it still doesn't sometimes.3) Nevertheless, my own personal experience and the experience of those of my patients who try this approach find that it's a rare flu or cold that will survive 2-3 rounds of taking vitamin C to bowel tolerance. This can be accomplished in a single, very long (and somewhat, but only mildly uncomfortable) day.

Dr. Pauling and his associates went on to speculate that some schizophrenics might be suffering from chronic subclinical infections. They claimed that they were able to ease the suffering of some of these folks by dosing them with large amounts of vitamin C. This therapeutic application was even more poorly received than the last. Part of the problem Dr. Pauling had in the 1950s was the political polarization of the day. Nutrition was associated with progressive social movements and in the 1950s this carried a more negative connotation than it does today. The ease with which nutritional therapies are defeated by poor research design makes it easy to produce follow-up studies that don't replicate early results. Dr. Pauling and his associates started their own journal.4

In any event I myself take 3-5,000 mg of vitamin C/day and find that whenever I do my thoughts become clearer and my mind more alert within a few moments. Those of my patients who also follow this regime as part of their nutritional program report that a wide variety of ailments, particularly those with inflammation as a component (as in chronic pain complaints) seem to be eased.

Oxidative stress is the term used by medical scientists to describe the effect on body tissues of over-exposure to oxidizing free radicals (aka: undersupply of antioxidants.) In the brain oxidative stress has been linked to chronic emotional stress,5 neurodegenerative disease,6,7 cognitive impairment8 and the dementia of aging,9,10 chronic fatigue syndrome,11,12 schizophrenia13,14 and autism.15,16

Vitamin C is important from at least two other perspectives. It's essential to the production of collagen, the gluey raw material for all kinds of connective tissue. Udo Erasmus, the author cited in the previous section, puts this very cogently. He says, "without vitamin C, we'd dissolve into puddles of cells on the floor."17 Vitamin C's free-radical clearing action is also critical to the RNA transcription process I mentioned with respect to trace minerals a few sections ago.18,19,20 Free radicals with their corrosive influence can play havor with the delicate dance of DNA, RNA and amino acids that's required to produce the proteins of hormones, neurotransmitters, enzymes and tissue replacement. That's another of the reasons cigarette smokers and alcoholics tend to age so quickly: the corrosive action of smoke and booze on the body not only attacks body tissues themselves but then inhibits the process of tissue replacement so the damage can't be repaired. This is how we get old before our time.


 1. Rayman, M.P. 2000. The importance of selenium to human health. Lancet. 356(9225):233-241.

 2. Brown, K.M. 2001. Selenium, selenoproteins and human health: a review. Public Health Nutrition. 4(2B):593-599.

 3. There is justified concern that the risk of kidney stones increases when gram amounts of vitamin C are consumed. This risk is ameliorated by the consumption of adequate magnesium. Taylor, E.N., et al. 2004. Dietary factors and the risk of incident kidney stones in men: new insights after 14 years of follow-up. Journal of the American Society of Nephrology. 15(12):3225-3232. In any event any risk would ensue from chronic consumption; the method outlined here involves very short-term use, generally less than 36 hours.

 4. Schizophrenia, later The Journal of Orthomolecular Psychiatry, and today .

 5. Cernak, I., et al. 2000. Alterations in magnesium and oxidative status during chronic emotional stress. Magnesium Research. 13(1):29-36.

 6. Rao, A.V., Balachandran, B. 2002. Role of oxidative stress and antioxidants in neurodegenerative diseases. Nutritional Neuroscience. 5(5):291-309.

 7. Gibson, G.E., Zhang, H. 2002. Interactions of oxidative stress with thiamine homeostasis promote neurodegeneration. Neurochemistry International. 40(6):493-504.

 8. Mecocci, P. 2004. Oxidative stress in mild cognitive impairment and Alzheimer disease: a continuum. Journal of Alzheimers Disease. 6(2):159-163.

 9. Deschamps, V., et al. 2001. Nutritional factors in cerebral aging and dementia: epidemiological arguments for a role of oxidative stress. Neuroepidemiology. 20(1):7-15.

10. Mattson, M.P. 2002. Oxidative stress, perturbed calcium homeostasis, and immune dysfunction in Alzheimer's disease. Journal of Neurovirology. 8(6):539-550.

11. Logan, A.C. Wong. C. 2001. Chronic fatigue syndrome: oxidative stress and dietary modifications. Alternative Medicine Review. 6(5):450-459.

12. Kennedy, G., et al. 2005. Oxidative stress levels are raised in chronic fatigue syndrome and are associated with clinical symptoms. Free Radical Biology and Medicine. 39(5):584-589.

13. Mahadik, S.P., Evans, D., Lal, H. 2001. Oxidative stress and role of antioxidant and omega-3 essential fatty acid supplementation in schizophrenia. Progress in Neuropsychopharmacology & Biological Psychiatry. 25(3):463-493.

14. Dakhale, G.N., et al. 2005. Supplementation of vitamin C with atypical antipsychotics reduces oxidative stress and improves the outcome of schizophrenia. Psychopharmacology (Berlin). August 13:1-5.

15. James, S.J. 2004. Metabolic biomarkers of increased oxidative stress and impaired methylation capacity in children with autism. American Journal of Clinical Nutrition. 80(6):1611-1617.

16. McGinnis, W.R. 2004. Oxidative stress in autism. Integrative Medicine. 3(6):42-57.

17. Erasmus, Udo. 1993. Fats that Heal, Fats that Kill. Burnaby, B.C.: Alive Books.

18. Gohil, K., Packer, L. 2002. Bioflavonoid-rich botanical extracts show antioxidant and gene regulatory activity. Annals of the New York Academy of Sciences. 957:70-77.

19. Cho, K.J., Yun, C.H., Packer L., Chung A.S. 2001. Inhibition mechanisms of bioflavonoids extracted from the bark of Pinum maritima on the expression of proinflammatory cytokines. Annals of the New York Academy of Science. 928:141-156.

20. Packer, Lester, interview with Richard Passwater. 2000. Whole Foods Magazine. Feb.