Get Something Free… Radicals The Saga of Vitamins A, C and E

The same oxygen you need to stay alive and to burn food for energy makes you oxidize just as fast as a rusty fender on the old jalopy in the back yard…or maybe in the driveway if your surname is Clampett at 90210. If your apples turn brown and your fish or butter becomes rancid, blame it on oxygen. Lungs, eyes, skin, fruits, vegetables, herbs, you name it. If it has cells, it’ll oxidize and those cells will change. But it’s a normal part of living. Fret not. The Creator gave us a way to intercept the free radicals and undo their dastardly deeds. These molecules are “free” because they have parts missing, and they scour the neighborhood looking for replacements, sort of like the original equipment manufacturer you look for when rebuilding your ’57 Chevy. Being on a mission, these molecules will rampage to hook up with another molecule and steal electrons. Frankly, it would be simpler if free radicals just killed a cell and left it at that. But nope, it has to start the dominoes falling. If a cell were bumped off, the body would make a new one. Instead, the cell’s DNA gets damaged enough to set the stage for disaster.

Broken DNA can make a cell mutate and set up a chain reaction for other cells to do the same thing. Not good. Free radicals damage a bunch of cells. Overexposure to the sun, cigarette smoke (either first-hand or second-hand), vehicle exhaust (diesel is the worst), comestibles that are called food but really are not, booze, heavy metals and a few other hazards can work over time to create chronic sickness, including cancer, heart disease, Alzheimer’s disease and Parkinson’s. How do we fix things? Maybe it’s easier to put the brakes on oxidation in the first place. Waddya think?

Antioxidants are molecules that work to prevent damage due to both normal body processes and exposure to some chemicals and environmental perils. One of the benefits of antioxidants is their ability to slow oxidation in the smallest parts of the body—proteins and DNA. There are antioxidants made by the body and those that come from food or supplements. The water-soluble ones react with oxidants in the blood and in the free spaces inside cells. The fat-soluble protect cell membranes from a process known as lipid peroxidation. Some body tissues might have more of one antioxidant than another. For example, one may be plentiful in the kidney, but almost absent from the heart, while the opposite might apply to a different antioxidant. Some may appear at the same concentration in every part of the body.

The body has its own antioxidant defense system, one that relies partly on minerals for proper functioning. Superoxide dismutase (SOD) needs copper, zinc and manganese; glutathione peroxidase needs selenium; and catalase depends on iron. Except for selenium, minerals are not defined as antioxidants, but as cofactors in their manufacture. Although this endogenous system demands respect, we’re going to focus on the most commonly used exogenous antioxidants—vitamins A, C, and E. In most activities, biochemical as well as psycho-social, the buck stops somewhere. With antioxidants, the buck stops at glutathione, so we’ll give that molecule the respect it merits, particularly for the work it does in the lungs (Rahman, 2006) (Nadeem, 2008).

Vitamin A is a general term for a group of related fat-soluble substances, including retinal and retinol, cited as preformed vitamin A. Retinal is converted to retinoic acid, the form that influences gene transcription. Beta-carotene and other carotenoids are referred to as provitamin A compounds. Beta-carotene, the carotenoid that comes from yellow and orange foods, is converted by the liver to retinol. Some forms of this vitamin are occasionally used in pharmacological doses to treat a few conditions, including retinitis pigmentosa (Berson, 1993), acute promyelocytic leukemia (Thurnam, 1999) (Ross, 1999), and various skin conditions (Ross, 1999). However, it’s important to realize that high doses of retinoids, especially if synthetic, can override the body’s own control mechanisms and present toxicities.

Preformed vitamin A is available as retinyl palmitate or acetate, overdose of which is easy to happen because people don’t read labels and often get the vitamin from more than one source, such as from a multi-vitamin or fortified food and later from a separate supplement.  The chief concern is that vitamin A is rapidly taken up, but slowly cleared from the body. Alcohol depletes vitamin A stores from the liver, but taking vitamin A while drinking is an accident waiting to happen. Keeping intake from a supplement at 2500 IU (750 mcg) should do the trick, while avoiding adverse effects on bone in the geriatric crowd. Getting vitamin A from foods is not normally a problem of overdose unless the food is fortified with it (Promislow, 2002). Beta-carotene, by the way, has about half the potency of preformed A, where 2 mcg of supplemental beta-carotene can be converted to 1 mcg of retinol. With foods, though, it takes 12 mcg to make 1 mcg of retinol. Can you see why it’s hard to overdose on cantaloupe?  Pumpkin, carrots, sweet potatoes, mangoes and collards are decent sources.

Water-soluble vitamin C is ascorbic acid, not citric acid, the latter made commercially by the fermentation of molasses. Even though citric acid can be found in oranges, there aren’t enough oranges on the planet to meet a fraction of the demand from the food industry.  Besides being an antioxidant, vitamin C is required for the synthesis of collagen, the structural element that holds us together. Additionally, it helps to make the neurotransmitter norepinephrine. Most animals can make the vitamin C they need; humans and guinea pigs cannot (Linster, 2007). Like all reducing agents, vitamin C itself becomes oxidized. Such an entity donates one or more electrons to a substance that already has become oxidized and is a free radical. In this instance, an antioxidant can become a damaging molecule, running around, looking for an electron to replace the one it just donated. But there is a rescue molecule, where the buck stops, as mentioned earlier. Too much ascorbic acid may cause kidney stones, since oxalates are metabolites of vitamin C, but doses up to 2000 mg a day shouldn’t be a concern for healthy people (Taylor, 2004) (Auer, 1998). The original RDA was barely enough to prevent scurvy, the reason for the RDA in the first place. Citrus, bell peppers, broccoli, potatoes, tomatoes, and strawberries are good sources.

Vitamin E is a fat-soluble family of eight antioxidants—four tocopherols and four tocotrienols. Any adverse publicity you read about vitamin E is based only on alpha-tocopherol, synthetically produced at that and administered to people with pre-existing conditions. The alpha- form of tocopherol is the one most often encountered because it’s actively maintained in the body and has the greatest nutritional significance, although the beat-, delta-, and gamma- forms have merit. It is an antioxidant that prevents the oxidation of fats (rancidity). This is especially important to the cell membrane. After vitamin E gives up an electron, it becomes a free radical itself, but vitamin C and A sacrifice themselves for its salvation. Besides being antioxidant, vitamin E appears to modulate some genes, to inhibit cell proliferation, and to control platelet aggregation and monocyte adhesion. It might even interact with enzymes, structural proteins and lipids (Zingg, 2004) (Ricciarelli, 2002), and regulate cell signaling (Rimbach, 2002). The body recognizes synthetic forms of vitamin E as sham, so it pays to find the d- form, not the dl-form. Oils, avocados and nuts are good sources. If there be a caveat, it is that too much can interfere with blood clotting. Therefore, if taking an anti-coagulant medication, check with the doctor before supplementing. If a tooth extraction or more serious surgery is in the offing, stop supplementation days ahead of time.

Once an antioxidant gives up an electron it can act like the thugs it’s trying to sequester. It needs its own savior. Here comes glutathione to the rescue. This is the body’s master antioxidant, made from amino acids.  As long as sulfur-containing amino acid stores are adequate and are regularly refilled through diet or supplementation (N-acetyl cysteine is such a source), glutathione is able to spare an electron here and there to replace the ones lost by vitamins A, C and E. The dysregulation of glutathione is known to be a prime factor in pathology, from diabetes to pulmonary fibrosis (Lu, 2009), so it pays to consume enough sulfur foods to get the methionine, taurine and cysteine that glutathione needs to keep itself in perfect form. The crucifers, onions and garlic, and animal products, including egg yolks, are substantial sources.

Having the best home run hitter in the league doesn’t guarantee a championship season. You need defense, too; you need a team. The same applies to antioxidants. The overall collection rather than the heavily advertised super antioxidant is what it takes because different antioxidants counteract damage by different types of free radicals within different cellular compartments. Natural and balanced is the rule.

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