Free radicals are extremely reactive molecules that can damage cell membranes, organelles, and DNA. Their destructive effects within the body make them an obvious target for therapeutic treatments. The most common types are reactive oxygen species (ROS), such as superoxide and hydrogen peroxide, and reactive nitrogen species (RNS), such as peroxynitrite. Free radicals are unstable because they have an unpaired electron. They become stable by stealing an electron from a nearby molecule. That molecule will then grab an electron from another nearby molecule, and a chain reaction ensues. Ideally, a free radical will come in contact with an antioxidant molecule before it can cause any damage. Antioxidants have a spare electron to donate, so they can neutralize free radicals before any harm is done.
Many environmental factors cause oxidative stress — solar or nuclear radiation, toxic chemicals and pollutants, infections, rancid fats, and more. When these stressors occur at levels beyond the body’s tolerance, a variety of health problems can emerge. Inflammatory diseases such as arthritis are linked to oxidative damage. Chronic diseases such as heart disease, cancer, Alzheimer’s, and diabetes are also associated with oxidative stress. The link between metabolic syndrome and ROS is an area of active research, as it is unclear whether oxidative stress is a cause or consequence of these disease states.
Free radicals are not always bad. Our immune system uses them to combat invading microbes. The process is a bit like tossing a grenade, though. The bad microbe gets destroyed, but your own cells take damage, too. Antioxidants can mitigate this collateral damage, but too high a dose interferes with the immune response.
Free radicals are also produced naturally in the body when mitochondria generate energy. Unhealthy mitochondria spew out greater quantities of free radicals, which normally marks them for destruction. Endogenous antioxidants produced by the body are the best defense against the ROS produced by mitochondria. Glutathione and superoxide dismutase are two potent examples.
The Vitamin Craze
Linus Pauling was one of the most renowned chemists of the 20th century. He won the Nobel Prize in two different fields (chemistry and peace) and authored thousands of papers. His work on molecular bonding was groundbreaking, and Francis Crick credited him as the father of molecular biology. In the 1970s, he was a leading proponent of the vitamin healing movement. His work in this area has largely been debunked, which begs the question of how such a brilliant scientist could be led astray.
Richard Feynman said the first rule of science is “you must not fool yourself and you are the easiest person to fool.” Nothing is more convincing than personal experience, even for a trained scientist. When Pauling was diagnosed with Bright’s disease, a condition that inflames the kidneys, he was treated with a low-protein, salt-free diet and some additional vitamin supplements. The treatment appeared to restore his health and sparked his curiosity about the potential role of vitamins in other diseases. He was especially enamored with vitamin C, taking up to 3 grams per day. That’s 30 times the recommended daily allowance for an adult male. It’s alleged he even added vitamin C to his orange juice.
Geniuses are often blinded by the seductiveness of their own ideas. Pauling was convinced that if oxidation is destructive, then antioxidants must be beneficial. Such a simple, elegant idea must be true, right? The modern-day evidence-based medicine movement warns against such reasoning from physiological mechanisms. A treatment must go through randomized clinical trials or other rigorous testing before it is considered validated. It can’t just look good on paper. It must work in the real world, under controlled conditions. Unfortunately for Pauling, when the evidence from trials was inconclusive, it didn’t sway him in the least. He never wavered in his conviction that vitamins, especially lysine and vitamin C, could be used to prevent colds, reverse heart disease, and prolong the life of terminal cancer patients.
One clear win for vitamin C is its prevention of scurvy — a horrific disease that inhibits collagen production. Collagen is the protein that makes up our connective tissues, and our body literally falls apart without it. On long voyages, it was once not uncommon for half or more of a ship’s crew to perish from scurvy. In the mid-1700s, Sir James Lind discovered citrus fruits could eradicate scurvy. The reason why remained unclear until the 1930s, when it was discovered that vitamin C was the mechanism behind the cure. Most animals can synthesize the vitamin, but humans, other higher primates, guinea pigs, and fruit bats cannot. To the extent we need it, it must come from our diet. Although, unlike the animals who can synthesize their own, we can resynthesize vitamin C from its oxidized form. This greatly reduces our need compared to other species who cannot recycle it.
Sources of Antioxidants
In The Anti-Inflammation Zone, Dr. Barry Sears describes three main types of antioxidants:
- Fat-soluble antioxidants are active on cell membranes, protecting them from free radical damage. They include vitamin E, beta carotene, and coenzyme Q10.
- Water-soluble antioxidants are able to move through the bloodstream and exit the body through urine. Vitamin C is the most common type.
- Surface-active antioxidants are a vital link in the chain because they shuttle free radicals between fat-soluble and water-soluble antioxidants, ultimately allowing the chain reaction to leave your body. Polyphenols are a type of surface-active antioxidant with thousands of known varieties. High concentrations are found in brightly colored plant foods.
It is widely recommended to “eat the rainbow,” because a diverse intake of different-colored plant foods will provide the full spectrum of antioxidants. Research suggests high-dose antioxidant supplements are ineffective or outright dangerous. It is speculated that a diverse intake of antioxidants might be more healthy.
Sears recommends an intake of polyphenols of 500 to 1,500 mg per day. He advises: “To give a sense of what 1,000 mg of polyphenols per day looks like, it could be approximately 5½ cups of broccoli, 1½ cups of blueberries, 2¼ cups of strawberries.” This approximates to 10 servings of fruits and vegetables per day.
Food manufacturers frequently tout the antioxidant levels in their junk food products. Fruit snacks for children often contain 100% of the recommended daily allowance of vitamin C. Livestrong says of Welch’s Fruit Snacks: “The overall nutritional value of Welch’s Fruit Snacks is considerable.” This is in spite of their being more than 40% sugar. Even if you strongly believe in the value of antioxidants, you should not make food choices on that basis alone. Antioxidants can’t beat a bad diet.
Your antioxidant needs are proportional to the amount of oxidative stress you are exposed to. In certain extreme cases, antioxidant supplementation can be helpful. Many antioxidant supplementation success stories are found in malnourished populations subsisting on grain-based diets. Such populations need to supplement with antioxidants to counter the effects of carbohydrate overconsumption and malnutrition. For example, vitamin A deficiency weakens the immune system and is the leading cause of preventable blindness. It’s especially common in poorer countries. About half of the blinded children die within a year. The World Health Organization cites a 23% reduction in overall mortality due to vitamin A supplementation.
Antioxidants have many benefits. However, when isolated from food products and packed into high-dose supplements, they rarely show any benefit in the human body and are sometimes harmful. Here is what some of the research has to say:
The failure of vitamin C supplementation to reduce the incidence of colds in the general population indicates that routine vitamin C supplementation is not justified, yet vitamin C may be useful for people exposed to brief periods of severe physical exercise. Regular supplementation trials have shown that vitamin C reduces the duration of colds [by 8% in adults, 12% in children], but this was not replicated in the few therapeutic trials that have been carried out.
In most cases, no effect of intervention was observed on mortality, except in specific subgroup analyses (e.g., sepsis and higher dose intravenous vitamin C). However, there have been few of these studies published to date, and even fewer of high methodological quality. Other commonly assessed outcomes included ICU and hospital length of stay, duration of vasopressor support and mechanical ventilation, and acute kidney injury. Some of the meta-analyses showed decreases in several of these secondary outcomes, while others showed no effect, depending on the selection criteria used for study inclusion.
- Antioxidant Supplements for Prevention of Mortality in Healthy Participants and Patients With Various Diseases
We found no evidence to support antioxidant supplements for primary or secondary prevention. Beta-carotene and vitamin E seem to increase mortality, and so may higher doses of vitamin A.
Some studies have shown potential harms associated with vitamin supplementation. One study that focused on smokers showed a 16% increase in lung cancer after beta carotene and vitamin E supplementation, and another showed a 17% increase in death after beta carotene and vitamin A supplementation. Numerous studies have shown increased risk of mortality among people who take multivitamins. These studies are observational and cannot prove cause and effect. Their outcomes may be due to the fact that sicker people are more likely to take vitamins. It’s also possible that low-quality supplements might have incorrect dosages or contain impurities. There is very little regulation or quality control in the supplement industry. Often, what is inside the pill bears little resemblance to the ingredients listed on the package.
In most cases, antioxidant supplementation represents a failed attempt to outsmart Mother Nature. Many would like to believe vitamins are magic pills that allow a person to thrive on a diet of Pop-Tarts and soda. Replacing the nutrients lost during industrial food processing is a band-aid solution to the myriad problems caused by those same highly refined foods.