Do we benefit by restricting calories? As I’ve mentioned before (see here), scientists for years
have known that a calorie-restricted diet, or simply eating less, improves the health and extends
the lives of laboratory species ranging from yeast cells to primates. But what about you and me?
If we limited our intake of calories, would we live longer and healthier? Whatever the answer, I
offer a guaranteed method to achieve both at the end of this post.

For obvious reasons, human experiments on calorie restriction have been limited, and necessarily
less controlled than animal studies. Those that have been reported (studies extending for up to
two years), haven’t been of sufficient length to draw any inferences on possible effects on life
span. Nevertheless experiments are ongoing, some showing positive health effects. So we may
benefit by limiting calories. For up to date information, click here.

Studies on human volunteers

Beyond that, any lengthy studies on human volunteers have basic weaknesses. Can
you guess what some might be? Just two months ago, a paper published electronically revealed
two weaknesses (called “challenges”) in its own study on human volunteers. I quote the paper’s
conclusion below (CR refers to calorie restriction).

Conclusion: The results highlight the challenges of: 1) setting a single CR goal vs. a range of
acceptable values, and 2) obtaining real-time and valid measures of CR adherence to facilitate
adherence.

What does #2 above mean simple English? It means a laboratory mouse gets its chow
metered out precisely by time and amount, so the experimental data collected from such animal
experiments are solid. On the other hand, a human volunteer in a long-term dietary experiment,
and safely at home away from prying eyes, could easily down an extra glass of wine, or substitute an
8 oz steak for the 4 oz specified, or even end his dinner with an unauthorized apple pie à la mode.
Who would be the wiser? Not the scientific investigator collecting the information.

Have calorie restriction experiments been properly interpreted?

Is it possible that the experiments on calorie restriction have been misinterpreted? Could another
factor in these experiments explain why “calorie restriction” improves health and extends lives?

Maybe so. Thanks to a magazine from my alma mater, I learned of recent experiments led by
Professor Dudley Lamming at the University of Wisconsin. He and his coworkers noted that
most experiments that imposed calorie restriction on mice have also included a period of fasting.
(In most earlier studies the animals had routinely consumed their daily ration within two hours of
their daily feeding and consequently endured a fast of about 22 hours each day.)

So what did Lamming and his colleagues do? They devised a method to separate the effects of
calorie deprivation from the effects of fasting. They accomplished this by studying
three experimental groups of mice, all of whom were calorie deprived for 16 weeks, and
comparing the end results with a control group of mice that ate a normal diet for the same time
period.

To simplify the results, two of the three groups of those calorie deprived mice ate their food
over multiple times throughout the day, but the third group was fed only once a day and devoured
the entire diet withing 2 hours. In short, this third group fasted for 22 hours each day.

Important result: of these three calorie-deprived groups, only the mice that actually fasted
developed typical changes of a calorie deficient diet. This indicated that the fasting, not the
calorie deficiency itself, had elicited the beneficial effects observed in earlier experiments.
Remember fasting and autophagy? (see here)

A Crucial Experiment

These investigators then followed up with an obvious experiment. They gave another group
of mice the full amount of food eaten by their control cohorts (thus no calorie restriction), but the
food was given to the mice all at once, and it was consumed over a 2-hour period. So these mice
fasted for 22 hours each day for 16 weeks, but never were calorie deprived. Results from these
mice were essentially the same as the group that had fasted while eating a calorie-deficient diet.
So 22-hour fasting by itself did the trick.

My simple summary of this important study doesn’t reflect the complex nature of much of its
content. Please understand that these experiments also employed several highly technical methods to
demonstrate an important truth.

You already know the basics. Our parents provided us with our unique set of 20,000-plus genes
(our genome, the DNA that make us who we are). But we must also remember that we have the
power to alter what our genes do, thanks to our epigenome, an extensive set of chemicals that
determines which of our genes are expressed, i.e., which are turned on, or off, that is whether
they are doing their job or staying silent. And we can influence our epigenome.

Adaptability of the epigenome

To demonstrate the adaptability of the epigenome, let’s return to the study of Lamming and his
colleagues mentioned above. These investigators measured gene expression in their fasting
fasting mice and compared those results with others from mice on a regular diet. The findings
astonished me. The researchers identified 2,700 genes in the liver and more than 1,800 genes in
fat tissue that were differently expressed in mice that had fasted when compared to the normal
controls. Fasting clearly produced huge effects on gene activity via the epigenome.

Although the study was performed on rodents, it has implications for you and me.
Clearly our genes are not all that matter. Our genes are regulated by our epigenome. And we,
by influencing our epigenomes, can impact our genes — and our lives.

A miracle worth pondering

So how do we influence our epigenome? Through our lifestyles, by what we eat and when we
eat, by how far and how fast we move, by where we go, and likely by nearly all we do. In short,
our activities influence our epigenome, some positively and some negatively (exercise plus,
smoking minus). Those changes in our epigenome affect our genes, which in turn influence our
health and our longevity. That chain of events, I think, is a miracle worth pondering, a miracle
that can be set in motion by every one of us.