First, when we take antioxidant supplements they go into our blood. Most of the free radicals and free radical damage isn’t in the blood. It’s deep within the mitochondria, the little sausage shaped organelles that are the power-generators within the cells. The supplements we take don’t make it into the mitochondria, so they’re not really effective in protecting them. If mitochondria get severely enough damaged, they die. If cells lose their mitochondria, they lose their power source, and they die. When enough cells die, we die.

Before we can understand how free radicals are created, we need to understand what happens to the food we eat. We know that food provides us with the energy we need to live, but most people don’t really understand how we use the food we eat. When we eat a steak, how do we use the energy contained in the steak to power ourselves? We use it to convert ADP into ATP. ATP (adenosine triphosphate) is the energy currency of the body. It is a molecule with high-energy phosphate bonds that when cleaved release the energy required to operate all of the body’s functions. ADP (adenosine diphosphate) is converted to ATP in the mitochondria. Energy is required for this process, and that energy comes from food.

Various metabolic pathways break down the food we eat and reduce it to high-energy electrons that end up in the mitochondria. These electrons are passed along from one complicated molecular structure to another along the inner mitochondrial membrane until they are finally handed off to oxygen, the ultimate electron receptor. (I’m really simplifying this process; entire books are written about it. I’m just giving you the most basic gist.) As these electrons are handed off from one complex to another, the energy they release during the transfer moves protons (hydrogen ions: H+) across this inner mitochondrial membrane. An electrochemical gradient is created when these hydrogen ions stack up on one side of the membrane. The electrochemical gradient is the force driving the production of ATP from ADP. Energy from food creates the electrochemical gradient, the electrochemical gradient drives the production of ATP, so, thusly, energy from food is converted into ATP.

As the high-energy electrons are passed along down the inner mitochondrial membrane they occasionally break free. When they break free, they become free radicals. These rogue free radicals can then attack other molecules and damage them. Because these free radicals are loosed within the mitochondria, the closest molecules for them to attack are the fats in the mitochondrial membranes. If enough of these fats are damaged, the membrane ceases to work properly. If enough of the membrane doesn’t work, the entire mitochodrium is compromised and ceases functioning. If enough mitochondria bite the dust, the cell doesn’t work and undergoes apoptosis, a kind of cellular suicide. This chronic damage and loss of cells is the basic definition of aging.

So, if free radicals cause this damage, why can’t we stop it with antioxidants? We do. But not the antioxidants that we take in supplement form–those don’t make their way into the interior of the mitochondria where the damage takes place. Nature has endowed us with our own antioxidant system located within the mitochondria where, so to speak, the rubber meets the road in terms of free radical damage. The antioxidants produced require sulfur, which comes from the sulfur-containing amino acids, i.e. methionine. There are certain substances contained in particular foods that stimulate the enzymatic machinery that increases the production of these intramitochondrial antioxidants. Sulforaphane, for instance, a substance found in broccoli sprouts greatly stimulates a particular enzymatic pathway within the mitochondria, resulting in an increased production of antioxidants where they need to be. Sulforaphane has been shown to prevent cancer, vascular damage, and a host of other disorders thought to result from excess free radical damage.
Our defense against free radicals, then, really comes in two forms. First, the production of antioxidants within the mitochondria, and, second, by making the fats in the mitochondrial membrane less prone to damage. How can we do that? By making them more saturated.

Sulforaphane was identified in broccoli sprouts, which, of the cruciferous vegetables, have the highest concentration of sulforaphane.^[1] It is also found in Brussels sprouts, cabbage, cauliflower, bok choy, kale, collards, Chinese broccoli, broccoli raab, kohlrabi, mustard, turnip, radish, arugula, and watercress.

Saturated fats aren’t prone to free radical attack–only unsaturated fats can be damaged by free radicals. Fats that have double carbon-carbon bonds, i.e. unsaturated fats, are the only fats susceptible to free radical damage. If the fats in the mitochondrial membrane are more saturated, then the membrane is less prone to free radical damage.

(Saturated fats: cream, cheese, butter, and ghee; suet, tallow, lard, and fatty meats; as well as certain vegetable products such as coconut oil, cottonseed oil, palm kernel oil, chocolate, and many prepared foods.)

Do we know this will work or are we guessing? We’re pretty sure this is the case for a couple of reasons. First, when animals are calorically restricted (so far the only sure-fire way to increase lifespan), their membranes become more saturated. It was first thought that caloric restriction would reduce the production of free radicals, but it turns out that it doesn’t. Calorically-restricted animals keep firing off free radicals at about the same rate as their non-calorically-restricted mates, but the fats in their membranes become more saturated, presumably providing protection against assault by free radicals, allowing the animals to live longer. Second, we can graph the degree of saturation of membranes against longevity, and when we do, we find that animals that live longer have more saturated membranes. Take a bat, for example, compared to a mouse. Both weigh about the same, but the bat lives for about 20 years, the mouse for three or four. The bat’s membranes are much more highly saturated than are a mouse’s.

How can we increase the saturation of our membranes? By eating more saturated fat. In papers I’ve read, authors have cautioned against this approach (not wanting to appear ‘nutritionally incorrect’ of course), then have gone ahead and written about how they created a group of study animals with greater membrane saturation by feeding them more saturated fat.

Another way we can increase the saturation of the fats in the membrane is by keeping insulin levels low. There are enzymes in the cells that both increase the length of fatty acid chains (called elongase enzymes) and those that desaturate (called desaturase enzymes) the fats. The desaturase enzymes can make fats less saturated. Insulin appears to activate these enzymes, so chronically elevated insulin levels would tend to keep the fats in the membranes less saturated and more susceptible to free radical attack. I would venture that this is one of the reasons that hyperinsulinemia shortens life. One of the constant findings in studies of centenarians is a low level of fasting insulin, which would make sense given the ability of excess insulin to make the membranes more prone to free radical damage.

Many people seem to think that the cellular membranes won’t function well if they contain more saturated fat. They believe that a more rigid membrane creates problems for the proper operation of all the receptors and other large protein structures that reside in the membrane. They are right in a way, since a certain degree of fluidity is necessary, but where I think they are wrong is in their belief that the degree of rigidity or fluidity of the membrane is determined by the degree of saturation of the fats in the membrane. It’s determined by methylation, as was discussed in the previous post.

When you put the whole puzzle together, it’s pretty easy to see why a whole-food low-carbohydrate diet works to maintain health and longevity.

It provides plenty of good quality saturated fat to help protect the cellular membranes from free radical attack. It provides plenty of methionine, which is both a source of sulfur for the antioxidants in the mitochondria and a source of methyl groups for methylation of the fats in the cellular membrane thereby keeping them more fluid while at the same time more saturated. And it keeps insulin levels low so that the fats are not desaturated more than necessary, once again keeping the membranes less prone to free radical damage.

(One other way that low-carb diets help with health and longevity is by keeping the cells de-junked. As we age junk proteins accumulate in the cells. Over time these junk proteins can compromise cellular function. The generation of ketone bodies, a common occurrence with low-carb diets, helps keeps the cells clean. See here for a previous post on the subject.)

I believe the first and most effective defense against free radical attack is a good diet. Second is moderate exercise. (The effects of exercise on free radicals could be another long post, but for now, take my word for it: exercise reduces the production of free radicals) Third is the addition of a few supplements. CoQ10 and lipoic acid both act as antioxidants, but more importantly, they serve to regenerate the bodies own antioxidants. And a good vitamin supplement without massive doses of specific antioxidants isn’t a bad idea.

I take krill oil, fish oil, and curcumin daily without fail. I also take a vitamin E daily to stabilize the fats in the fish and krill oil. I take CoQ10 and lipoic acid several times per week. I take a multivitamin every now and then. And I take vitamin D3 in large doses throughout the winter. From time to time I take this or that other supplement depending upon what’s going on with my health, i.e. do I feel like I’m getting a cold?

I’m not a big fan of large doses of specific antioxidants because we weren’t evolved to take them. Plants live in the sun and produce oxygen as their way of life. Both the sun and oxygen are harmful if not controlled. Plants have evolved a complicated antioxidant system to protect themselves from sun and oxygen damage. We consume these antioxidants when we consume plants. We get tiny amounts of a zillion different kinds of antioxidants, not massive amounts of single antioxidants. And we get all the raw materials for the production of our own antioxidants from meat. (This post has gone on long enough, so if you want to read more about my view on antioxidants, read Chapter 5 in the Protein Power LifePlan.)

In my view, this is how nature intended us to get our antioxidants, and, with the exceptions mentioned above, this is the way I intend to get mine.