A Matter of Life & Death: Antioxidants and the Morbidity Index

The Ratio of Reduced and Oxidized Molecules Predicts Recovery from Disease

Disorders marked by oxidative stress cause large shifts in the amounts of reduced (antioxidant) and oxidized nutrients. The antioxidant form plummets, and the oxidized form rises. Recovery is marked by a shift toward the antioxidant form. This has already been demonstrated in the case of vitamin C, and it now appears to be the case with coenzyme Q10. This simple and powerful truth has been overlooked by medicine and science.

Millions of molecules move swiftly between oxidizing and reducing (antioxidant) states in our bodies all the time. An oxidizing agent receiving electrons becomes a reducing agent (thus, for example, coenzyme Q10 in its antioxidant form can donate electrons to vitamin E after it has been oxidized and recycle that vitamin E so that it is once again in its electron-rich, antioxidant form). A reducing agent offering electrons becomes an oxidizing agent once it has given up its electrons. Thus, oxidizing and reducing agents form what science calls a redox couple. They do a dance of giving and receiving. The terminology can be a bit confusing to a layperson, but to sum it up: antioxidants are electron-rich and in that antioxidant form they are called “reduced”, and can donate those electrons to stabilize free radicals. Oxidized substances have already lost their electrons. Free radicals are generally unstable, oxidized compounds. They need electrons to become stable. In their unstable, free-radical form, some of them are powerful killers of pathogens.

Interestingly, the ratio of antioxidant (reduced) to oxidant (free radical) in the body seems to be a very important marker of health or illness. Take ascorbic acid, perhaps our most potent water-soluble antioxidant, as an example. Disease lowers the reduced form of ascorbic acid to such a degree that one may predict morbidity and mortality based on the ratio of antioxidant (ascorbic acid) to oxidized (dehydroascorbic acid) alone. It’s of great interest that we now know the ratio of reduced (ubiquinol) to oxidized (ubiquinone) CoQ10 also changes radically in disease.

With vitamin C this ratio is so predictive we can predict, in very ill patients, those who will recover from life threatening illness. We need more data on coenzyme Q10 to expand this picture to lipid soluble antioxidants. When you see data as consistent as this, you begin to get the sense that health and longevity depend on keeping the reduced form of antioxidants at high levels, with continuous and effective recycling of the oxidized form.

Back in 1985, Stephen Levine, Ph.D. & Paris Kidd, Ph.D. published a landmark text called Antioxidant Adaptation: Its Role in Free Radical Pathology. Many of the insights in that 400 page text, now in its fourth printing, have been supported and confirmed again and again by subsequent research. As the authors noted then, ascorbic acid is a diagnostic and prognostic tool. As far back as the 1930’s, researchers were able to determine the amount of reduced (the electron-rich, antioxidant form) ascorbic acid in the blood. But in 1943, new research methods were introduced that measured the total level of ascorbic acid. This was deceptive, because it included not only the reduced form, but also the oxidized (dehydroascorbic acid), along with other decomposition products of vitamin C. In 1955, researchers pointed out that both the antioxidant and the oxidized form of vitamin C could protect from scurvy at low levels, but that at high levels the oxidized form was toxic. In fact, as sick patients became sicker, and finally died from illnesses such as meningitis, tetanus, pneumonia, and typhoid fever, the antioxidant form of ascorbate plummeted while the oxidized form rose.  In fact, many dying patients had higher “total” levels of ascorbate (both forms) than survivors. The magical “key” lay in the ratio, which the authors termed the morbidity index.

Look closely at Figure 7. The difference in the ratio is astounding. Healthy individuals had a morbidity index of about 14—which means approximately 95% of the vitamin C is in the antioxidant, reduced form. This is parallel to the new findings on CoQ10, although a healthy individual taking high levels of ascorbic acid would have an even higher index. In contrast, those who were critically ill but survived, had a morbidity index of about 1, while those who died had even less—a mere 0.3 to 0.5. During convalescence, the morbidity index tripled or even quintupled, rising to 3.0 to 5.0.

Now take a look again at the ratio of ubiquinol (reduced) to ubiquinone (oxidized) in common diseases where oxidative stress is high. In diabetes, the percentage of ubiquinol plummets from about 95% to 29% as blood glucose rises (Figure 3) [in the CoQ10 Breakthrough article]. Diabetics have an astounding 75% less ubiquinol overall compared to healthy individuals.

There is an elegant logic to this striking correlation, and we are likely to find it with other significant antioxidants as well. Both ubiquinol and ubiquinone, and ascorbic acid and dehydroascorbic acid, are part of the body’s oxidation-reduction system. Ascorbic acid is known to be one of the most potent redox stabilizers in the body. In turn, CoQ10 is our most potent lipid-soluble antioxidant, and the key antioxidant in the mitochondria. The fact that in both cases, healthy individuals seem to maintain 95% of Vitamin C and coenzyme Q10 in their reduced, antioxidant form is compelling data. To maintain health, we believe the ratio must favor high amounts of reduced, or antioxidant, forms of nutrients. Vitamin C had long been available as a supplement in its reduced form, and now we have the reduced form of coenzyme Q10 available as a new supplement. Armed with these and other important nutrients, we may be on the verge of truly utilizing the power of antioxidant adaptation.

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