The Nutraceutical "Rejection - Need" Theory of Aging
Stephen L. DeFelice, M.D.
During 1965, while conducting the first clinical trial in the
United States on the natural substance carnitine, I became interested in
the aging process and ways to reverse it or slow it down. My interest
arose because the most obvious hallmark of aging is the loss of energy
from body cells. Since carnitine naturally increases cell energy, I
wondered whether it and other natural substances could replenish the
lost energy of the aging cell. Also, many disease states are
characterized by a loss of energy, and I saw no reason not to consider
aging like any other treatable disease. In those days, however, it was
difficult to find a single colleague who would agree with me. It was
simply too out of the box an idea to be accepted in the academic medical
– scientific world, let alone our society in general.
Leaping forward four decades, the scenario has changed
dramatically. We now know lots more about the aging process which has
opened exciting doors and opportunities. Laboratory studies on genes,
the epigenetic environment and caloric restriction clearly indicate that
someday new anti – aging discoveries will be made.
However, though I may be wrong, they are not on the near term
horizon. But there is one near – term possibility based on what I label,
The Nutraceutical “Rejection – Need” Theory of Aging. A nutraceutical
is a food or part of a food that has a medical – health benefit
primarily with respect to the prevention and treatment of disease.
Bottom line, we are talking about dietary supplements be they in a pill,
liquid or food dosage form.
Let’s return to carnitine. This natural substance has significant
positive clinical effects in a number of diseases ranging from the FDA
approved fatal condition of carnitine deficiency in children to renal
dialysis patients. It has also been demonstrated that, in a number of
clinical studies, it effectively protects the heart against the lack of
oxygen due to coronary heart disease. Unfortunately, it has not been
developed for FDA approval for this cardiac condition, the number one
killer in the United States, because of prohibitive economic reasons. It
is important to note that all of these conditions are associated with
cellular carnitine deficiency. When, however, carnitine is given to
normal or healthy people there is little or no effect.
I first observed the latter in my second clinical trial with
carnitine in 1966, which observation has since been confirmed in other
studies. A number of years later, after some of the aforementioned
clinical studies were published, it first dawned on me that carnitine is
clinically effective only when there is a cellular “need” and
“rejected” when there is not. The cells are deficient, ergo, the “need”
and the rationale for the resultant activity.
But, in those days, I was thinking of carnitine alone, not of
other substances, until the first large, controlled clinical study
evaluating the effect of vitamin C on the common cold proved to be
negative. Then came the second dawning: I thought that, like carnitine,
there is no cellular “need” for vitamin C in common cold patients as
there is in those with scurvy, a vitamin C deficiency state, which
responds dramatically to supplementation with this vitamin. And the
“rejection-need” phenomenon may be true of many other nutraceuticals.
Then there followed disappointing clinical results of beta
carotene for lung cancer and vitamin E for cardiovascular disease, among
others, most likely due to the absence of a “need” and, for that
reason, were “rejected” by the cells.
During the aging process the furnaces of the cells, the
mitochondria, where nutrients are metabolized to produce the ATP
molecule or energy, progressively produce less energy with the passing
of time. Free radical or oxidant activity is thought to play a
significant role in this process. The rationale behind the Nutraceutical
“Rejection – Need” Theory of Aging is to increase the energy levels in
the mitochondria of old cells by creating a “need” for these cells to
use nutraceuticals that are involved in ATP production and availability
as well as reduce oxidant activity. One way to accomplish this is to
stimulate them with substances such as growth hormone and testosterone
given along with the nutraceutical formula containing substances such as
carnitine, magnesium and CoQ10, all three substances involved in ATP
activity, and carefully selected antioxidants. Proper dosing of all
ingredients is critical in order to optimize the chances of success.
The encouraging news is that, in clinical studies in the young and
old, both of these hormones have shown “stimulating” activity including
increasing the size and number of muscle cells and improvement in
cognition. The theory is that the nutraceutical formula will add to
these effects by being utilized by the cells due to the stimulant
The following is a revealing sequel: During mid 2005, I decided
that there were sufficient scientific and medical data to justify a
clinical study to test the theory in elderly volunteers to determine
whether both the physical and mental deterioration of the aging process
can be reversed to some degree. The next step was to consult with a
number of experts on the merit of the theory and the design of the
clinical study. All were helpful, most highly enthusiastic, and the one
that had intellectual doubts about the theory still urged me to go
forward with the clinical study.
Then I met with one of the world’s leading clinical researchers
located at a major U.S. university. He was quite excited about the
theory, and he designed a highly sophisticated aging - reversal clinical
study that would give us many answers regarding the effectiveness and
safety of the treatment.
Because of the promise that the treatment may work to help the
elderly, a clinical study to test the theory is urgently needed. I have
placed this article on the FIM website with the hope that it will be