The title may be ill-conceived, belying the scientific merit of the book. In fact, this is required reading for anyone seriously interested in anti-aging medicine. It presents cutting-edge information about how antioxidants work as a team, affecting every system and every cell in the body, including even our DNA-why "everything does everything."

Dr. Packer has been dubbed by his colleagues "Dr. Antioxidant" because of his dedication to the field, as attested by nearly five decades of research into the biochemistry of antioxidants and hundreds of scientific papers. Packer proposes that antioxidants work in the body not singly, but as a network, and that "the sum is greater than its parts." Antioxidants synergize with each other and, even more important, recycle each other.

"What makes network antioxidants so special is that they can greatly enhance the power of one another," Packer explains. Coenzyme Q10, for instance, enhances the action of vitamin E. Packer suspects that some of the effects ascribed to CoQ10 are due primarily to its potentiation of vitamin E. Thus, it is very difficult to study the effects of a single antioxidant; the whole network is affected, and it is the whole network that produces the manifold effects that we see. Forget the idea of a single antioxidant; it takes the network.

True, Packer is not the first expert to recommend taking many antioxidants together. But while others have been recommending taking a wide range of antioxidants, since they "work together," and thus may have hinted at the network effect, Packer deserves the credit for crystallizing the concept of "network antioxidants." He is emphatic and uncompromising about the importance of synergy among various antioxidants. In vivo, a single antioxidant does not act alone; the whole network becomes involved. The whole network is the "antioxidant miracle" that protects us against disease and slows down aging.

Packer is convinced that his lab's discovery of how antioxidants work as a network will have far-reaching consequences. He even states, "Just as the discovery of penicillin changed the practice of medicine earlier in this century, the antioxidant network has the potential to create a new paradigm for health." I applaud the uncompromising spirit of this statement. Far from merely rehashing well-known facts, this is in fact a pioneering book.

Back to top

Network antioxidants:
a mutually recycling "juggernaut" against the lethal forces of oxidation

Packer shows this particularly in regard to the five pivotal antioxidants that he calls "network antioxidants": lipoic acid, coenzyme Q10, vitamin C, vitamin E (all natural varieties of it, not just alpha tocopherol), and glutathione. To see why these work together as a network, let's review the basics.

A free radical is a molecule with an unpaired electron, seeking to strip an electron from another molecule, and thus having the capacity to damage vital compounds such as lipids and proteins. An antioxidant is basically an electron donor: it can quickly "disarm" a free radical by easily giving up one of its electrons. But in the process, the antioxidant itself becomes a weak free radical. Fortunately, if other antioxidants are present, the original electron donor can be "regenerated," or restored to its antioxidant status.

This point is crucial to understanding Packer's thesis. In the course of its normal activity, an antioxidant becomes a pro-oxidant, i.e. a free radical (although a less destructive one than whatever free radical it has just disarmed); it must be recycled to its antioxidant state by other antioxidants. Hence the idea of a self-recycling network of antioxidants, rather than antioxidants working individually. Hence also the practical implication: in order to maintain the high levels of antioxidants necessary for health and longevity, it is necessary to ensure optimal recycling of the key antioxidants. How? By taking the whole range of certain crucial antioxidants.

Packer states that the network antioxidants include lipoic acid, Coenzyme Q10, vitamin E, vitamin C and glutathione. These work as a team, constantly regenerating each other from the oxidized state back to the antioxidant status. The pivotal antioxidant is lipoic acid. It not only recycles all the other network antioxidants, but it also regenerates itself. Although it is produced in the body, the production declines with age, and becomes insufficient to provide full benefits. Adding lipoic acid to one's supplement regimen means boosting the levels of all the other network antioxidants.

This is particularly important in the case of glutathione, since most experts agree that oral glutathione does not get absorbed through the intestines. Unfortunately Packer does not comment on the idea that taking glutathione with sufficient anthocyanins, for instance a high-potency bilberry extract, would protect it from oxidation in the gastrointestinal tract and thus make it available to various tissues. Even so, only some types of tissue can absorb preformed glutathione-most cells must synthesize it. Packer's lab discovered that lipoic acid can boost the levels of glutathione by up to 30%. Thus, in Packer's view, it is necessary to take only four network antioxidants: lipoic acid, CoQ10, vitamin E (including tocotrienols) and vitamin C. It might also be desirable to include mixed carotenoids and various mixed polyphenols.

One reason why it is so important to maintain high levels of glutathione is that it is crucial for the detoxification of carcinogens. Packer states that most people do not inherit "cancer genes"; rather, they have a genetic weakness in their detoxification system. Glutathione is an extremely important part of the detoxification system, and thus of our defenses against cancer. Lipoic acid in particular, as well as various other antioxidants including N-acetyl-cysteine (NAC), can raise glutathione levels, making cancer less likely, even if it happens to run in the family. Interestingly, whey protein has also been found to raise glutathione levels. Certain flavonoids, including grape seed extract and bilberry, likewise boost glutathione levels; silymarin, a flavonoid found in milk-thistle, is valued for its ability to raise glutathione levels in the liver. It is too bad that Packer does not discuss the glutathione-flavonoid sub-network.

Glutathione may also be one of the most important keys to longevity. Centenarians have been found to have higher levels of glutathione than would be expected for their age. Boosting one's glutathione levels with lipoic acid, NAC and flavonoids should be one of the first items on anyone's anti-aging agenda.

When all the network antioxidants are present in sufficient concentrations, the result is a marvelous synergy in the body's unceasing battle against the forces of destruction represented by excess free radicals. In Packer's and Colman's words, "when combined, [the network antioxidants] create a juggernaut against the lethal forces of oxidation."

Besides championing the use of lipoic acid as the pivotal network antioxidant, Packer also stresses the importance of gamma tocopherol, and particularly of tocotrienols. Found naturally in cereal bran and tropical oils, tocotrienols are chemically very similar to tocopherols, except for a difference that gives them special powers. They are more mobile and distribute evenly throughout membranes; tocopherols tend to cluster. They also have much greater "staying power," since they are 40 to 60 times more readily recycled. Tocotrienols are also more unsaturated, which makes them more powerful antioxidants. We are now discovering their special ability to prevent cancer and clean the arteries of plaque.

Likewise, Packer points out the newly discovered importance of gamma tocopherol. It is gamma tocopherol, not alpha tocopherol, that is depleted in AIDS patients, cardiovascular patients and smokers. This situation is particularly disastrous for smokers, since gamma tocopherol shifts the metabolism of nitrogen dioxide into the production of non-carcinogenic compounds. Gamma tocopherol also protects against high blood pressure, and thus lowers the risk of heart attack and stroke. It turns out that one of its metabolites, LLU-alpha, is a natural diuretic.

The vitamin E family has been receiving more and more "rave reviews." The crucial anti-aging question is, "Do people who take vitamin E live longer?" Packer replies, "All signs point to a resounding yes." In Packer's words, we have "wonderful evidence" that vitamin E slows down the accumulation of the age-pigment lipofuscin, a waste product of lipid peroxidation, and can in fact dramatically extend the number of times cells can divide before they die-the so-called Hayflick limit.

How is this possible? In-vitro studies have shown that the telomere ends of chromosome are especially vulnerable to damage by free radicals. This is at least one cause of their shortening during cell division. By lessening the degree of free-radical damage, antioxidants can keep the telomeres relatively long for a longer period of time. This implies that far from being an absolute, the Hayflick limit is subject to anti-aging manipulation. The implications for life extension are enormous.

Back to top

Mixed carotenoids: the synergistic effect

Carotenoids also constitute their own network, working synergistically with one another. For example, mixed carotenoids enhance immune function better than beta carotene alone. The antioxidant power of mixed carotenoids is enhanced particularly when lycopene and lutein are included. One of the most interesting sections here is "The rise and fall of beta carotene," in which Packer explains the disastrous results of unbalanced supplementation, at least in smokers, who are under a particularly heavy barrage of free radicals. He points out that mixed carotenoids, the way they are naturally found in vegetables and fruit, have been consistently found to protect against lung cancer, as well as many other types of cancer.

While beta carotene has fallen into relative disfavor, lycopene has emerged as a very potent antioxidant, if not quite yet a rising star on the health food store shelves. It is too bad that Packer does not discuss lycopene in greater detail. He does point out that in vitro it is a stronger antioxidant than beta carotene, and that it inhibits the growth of various cancers. But why is lycopene so important, and how do carotenoids synergize as a network? Is it really the metabolites, such as carotenoids and retinoids, that should be studied? And under what conditions do carotenoids become pro-oxidants capable of promoting cancer-only in those who smoke more than 20 cigarettes a day, or should the average person be concerned? This is perhaps the least satisfying chapter in the whole book, which is understandable, since Packer's main area of study has been lipoic acid and vitamin E, and the main network antioxidants in general. That's where he shines.

Packer also singles out flavonoids as important "boosters" of the main network antioxidants. Again, a more extensive review of flavonoids would have been preferable, since there is potentially a bigger story here than simply playing a supportive, "boosting" role. Flavonoids are extremely powerful antioxidants in their own right; some are capable of quenching the hydroxyl radical. Packer acknowledges that this is extremely important, since the hydroxyl radical is the most dangerous, capable of directly damaging DNA.

Back to top

Are flavonoids merely "boosters?"

Flavonoids' boosting role certainly deserves attention: proanthocyanidins and anthocyanidins in particular-Pycnogenol and grape seed extract, bilberry-boost the levels of vitamin C, vitamin E and glutathione. Fortunately Packer does provide some intriguing information that goes far beyond that. For instance, one of the most important functions of flavonoids is their ability to control the levels of nitric oxide, which turns extremely harmful and pro-aging when present in excess. In fact, there even exists a "nitric oxide hypothesis of aging." Again, complex mixtures of flavonoids, such as are naturally present in ginkgo, for example, turn out to have synergistic power, beyond that of the individual components.

Still, both experimental studies done on animals and human epidemiological studies hint at a truly starring role for flavonoids. These weak plant estrogens happen to be ferocious phenolic antioxidants. There are very good reasons to think that a sufficiently high daily dose of flavonoids-from berries, apples (quercetin), onions, tea, wine, chocolate, miso, even coffee, and/or from supplements (bilberry, grape seed extract)-might give us lifelong freedom from heart disease, cancer, cataracts, and the nightmarish neurodegenerative diseases such as Alzheimer's and Parkinson's disease. Epidemiological studies confirm, or at least suggest, that the higher the flavonoid consumption, the lower the rates of cardiovascular disease and cancer, and the higher the life expectancy (this shows even for moderate wine drinkers as opposed to tee-totalers). As Packer himself states in a no-doubts-about-it section heading, "Flavonoids slow down aging." The public urgently needs to be made aware of this. And of course no life extension regimen makes any sense without including generous doses of flavonoids.

Since the supplement industry has given us " B Complex," I hope that soon we will also have "E Complex," "Carotene Complex" and perhaps "Flavonoid Complex." Once the network concept takes hold, I think it should be only a matter of time.

Continue to page 2 of 2