Our Longevity Diet

In the past I’ve heard several claims that intermittent fasting can help prevent cancer, but in following the scientific literature, I’ve seen little evidence behind this claim. Now, someone from a discussion group brought this study to my attention:

Adult-onset calorie restriction and fasting delay spontaneous tumorigenesis in p53-deficient mice

Basically, the study not only shows that both calorie restriction and fasting can help make significant delays in the onset of cancer in mice bread to develop that disease (that’s what the p53 deficient part means), but they also show that the effect is present even when the calorie restriction or intermittent fasting is started later in life, rather than at adolescence. Too many of the existing studies of CR and IF look at the effects on animals that begin in adolescence and continue throughout their lives. I’d like to see more studies examine the effect of starting these dietary protocols later in life, and also the effect of starting early in life but then abandoning the protocol to return to ‘normal’ (i.e. continuous) eating.

And while the study shows cancer was ‘delayed’ rather than prevented, the difference is only semantic. Delay cancer long enough that you die of something else, and it has effectively been prevented. The mice were genetically prone to develop cancer — unless you have Li-Fraumeni Syndrome you are probably not so prone.

This study did show that calorie restriction was more effective than intermittent fasting, but the intermittent fasting regime used involved fasting just one day per week — it would be more interesting to see the results if ADF (alternate day fasting) were used. The bottom line seems to be that it is never too late to start benefiting from intermittent fasting. The beneficial effects are probably much stronger for those who start in early adulthood, but even us old fogies can reap some benefits.

A study reported last month noted that researchers have known for a while that Type II Diabetes is associated with high levels of visceral (or Belly) fat, while subcutaneous fat (below-skin, especially in hips and buttocks) is not. The study found, surprisingly, that it was not the presence of belly-fat so much as the absence of subcutaneous fat that leads to diabetes. That is to say, visceral or belly fat does not have a negative effect, but rather subcutaneous fat has a positive effect on insulin sensitivity, which in turn correlates with the development of Type II Diabetes.

People who have high levels of both types of fat are at much lower risk for diabetes than those who have only belly fat. And those with only subcutaneous fat are even less likely to develop diabetes. The researchers suggested that subcutaneous fat may produce certain hormones, called adipokines, that produce beneficial metabolic effects.

Now another study was released that says pretty much the opposite:

Our study found lipid release from abdominal fat was substantially elevated during the night, which may be a primary mechanism leading to insulin resistance, a strong risk factor for type 2 diabetes.

This study seems on shakier ground, so far as the basic logic goes. They observe that belly fat releases lipids, and jump to the conclusion that this is related to insulin resistance — without any proposed (let alone observed) mechanism for it to do so. It is an observed correlation, with no known causality relationship.

This is a good example of why following the scientific studies can be so confusing. You need to look critically at these reports, and judge the probability of their being accurate. But often we lack the detailed information on study design and implementation that would allow us to accurately judge the results.

In any case, we may assume that if lipids from belly fat were related to insulin resistance, then intermittent fasting may exert a positive effect by limiting the release of lipids during fasting periods. Of course, that is just speculation — but it is consistent with the observed beneficial effect of intermittent fasting on insulin sensitivity.

A report today describes the autopsy results for the examination of the brain of a woman who died at the age of 115 years. There were absolutely no signs of atherosclerosis (narrowing of the arteries) or beta-amyloid deposits (a characteristic of Alzheimer’s disease).

The woman had undergone neurological and psychological examinations at the age of 112 and 113, and showed no signs of dementia or problems with memory or attention at that age. She was alert and involved, interested in national and international politics. She lived in a residential care home from the age of 105 due to poor vision, but her brain and intelligence compared favorably with people forty years younger.

I have not found any detailed biographical reports on this lady, so we don’t know her economic status or life history, but from her age we know she lived through the trying times of World Wars I and II, as well as the Great Depression. It is not too far-fetched to imagine that she experienced some caloric restriction and/or involuntary fasting during those years.

I have yet to see any studies on intermittent fasting that allow the subjects to go back to unrestricted diets after a period of time, and still continue to follow-up on health and longevity measures. My impression from the study reports we do have, however, make me think that calorie restriction or intermittent fasting during early adulthood may be more beneficial, in the long run, than the same diet initiated later in life. By the time we reach middle-age, much of the damage is done already.

Whatever the cause of this woman’s longevity — lucky genes or just a freak of nature — she is proof that degeneration of the brain is not an inevitable consequence of aging. Other studies show that challenging the aging brain to learn new things is one way to help stave off deterioration. We are hoping intermittent fasting will also help.

Clearly, we should not need to make an either-or choice, but scientists wanted to know which was better for a long life: calorie restricted diet, or exercise? The research clearly shows caloric restriction is more beneficial for life extension than exercise.

The first caveat is that they were looking at mice, and however similar the mammalian physiology can be at times, mice are not humans. Second, note that this study looked at caloric restriction — not fasting. Now other studies have shown that fasting can confer all of the same benefits to health and longevity that calorie restriction does, but fasting was not examined in this study.

Earlier research had already shown that while rodents that got exercise lived longer than those that did not, it was the average lifespan that was longer, not the maximum age at death. So exercise helped prevent early death in some percentage of animals, but did nothing to extend the lifespan beyond the normal.

Comparing calorie restricted animals to those that got lots of exercise, the calorie restricted animals lived longer, exceeding the ‘normal’ average lifespan for the species. The purpose of this latest study was to see if they could find the reason behind these earlier results.

In the newly reported study, mice that ate as much as they wanted and got little exercise had the highest levels of insulin-like growth factor (IGF-1), while both exercise and calorie restriction lowered that. Insulin itself was high in both animals that ate freely and those that ate freely and exercised. Both exercise and caloric restriction lowered 8-hydroxyguanosine (8-OHdG) levels, the presence of which is indicative of DNA damage. In summary, only insulin levels were clearly associated with the longer life expectancy, though researchers are not suggesting that insulin alone was responsible for the difference.

The authors suggest that reducing calories produces beneficial changes in ‘hormone levels’ without being too specific about which hormones. The analysis goes on to say:

A handful of studies comparing calorie restricted people to people who are avid exercisers, found similar hormonal benefits among those eating less. However, calorie restriction studies are difficult to carry out in people because participants often complain of feeling hungry, lethargic, and cold.

Well yes, calorie restriction is difficult for humans. Why not study intermittent fasting instead? A properly scheduled intermittent fast without caloric restrictions is very easy to follow. Intermittent fasting with mildly restricted calories is also easier than the typical caloric restriction diet — which has people eating all the time, but too little food to ever be satisfied. Better a small eating window daily, and fasting the rest of the time. You can eat one satisfying meal, at least, which makes the entire process more tolerable. Finding enough randomly selected individuals for prolonged caloric restriction studies will be nearly impossible — the drop-out rate will skew any data collected. Intermittent fasting without calorie restriction is so easy, however, that a large study could be undertaken with no more difficulty than in any other human-based studies that require modified behavior.

It was a study released five years ago that inspired us to try intermittent fasting. I looked into the scientific literature behind life extension in 2002-2004, and came away with the conclusion that the only certain road to a longer, healthier life was to cut caloric intake drastically. To me, that seemed far to ascetic an approach to life. Even if it didn’t make you live longer, it would sure seem longer. I want to enjoy life, not suffer through it.

Then while browsing the web looking for something else entirely, I came across a reference that led me to a study called (oh so succinctly) Intermittent fasting dissociates beneficial effects of dietary restriction on glucose metabolism and neuronal resistance to injury from calorie intake. The abstract was a bit more clear:

Dietary restriction has been shown to have several health benefits including increased insulin sensitivity, stress resistance, reduced morbidity, and increased life span. The mechanism remains unknown, but the need for a long-term reduction in caloric intake to achieve these benefits has been assumed. We report that when C57BL/6 mice are maintained on an intermittent fasting (alternate-day fasting) dietary-restriction regimen their overall food intake is not decreased and their body weight is maintained. Nevertheless, intermittent fasting resulted in beneficial effects that met or exceeded those of caloric restriction including reduced serum glucose and insulin levels and increased resistance of neurons in the brain to excitotoxic stress. Intermittent fasting therefore has beneficial effects on glucose regulation and neuronal resistance to injury in these mice that are independent of caloric intake.

Note that last line. Glucose regulation is a very important health factor, that leads to diabetes when it goes awry. Neuronal ‘resistance to injury’ is basically saying that the brain deteriorates more slowly — so Alzheimer’s and Alzheimer-like diseases are held at bay for a longer period. This was enough to spark my interest. I began to read about the effects of intermittent fasting, and found other benefits cited, some of which I’ll mention in future posts.

When it comes to implementing the fast, I found several schools of thought. Some people fast the same time every day, so they have 20 hours fasting and four hours eating, for example. Others skipped breakfast and lunch one day, and skipped dinner the next — leading to an imbalanced pattern of more calories one day and fewer the next. Others practice ‘alternate day fasting’ and eat normally one day, then either nothing the next, or a very small meal of 300 to 500 calories. Again, a very imbalanced pattern that seemed like it would be difficult to follow.

Luckily, since we live in Mexico, we were already used to eating our main meal in the early afternoon — much earlier than the typical Euro-American diet. So our solution, which I’ve described in other posts, came as a natural approach that more nearly simulates what the experimental mice experienced. Remember: “their overall food intake is not decreased and their body weight is maintained” — so they were not calorie restricted, but stilled showed the health benefits (including, in other studies, longevity). We want that! We are not obese, so while a little weight-loss would be nice, the extreme restrictions of alternate day fasting are just too difficult to maintain for the rest of our lives. Our style of intermittent fasting works. We have lost some weight, and only time will tell if that continues (we only report our weight in this blog monthly, to avoid the confusion of minor fluctuations). But we feel better, and have no qualms about keeping this lifestyle for many, many years to come.

So far, I have not found any clear description of who came up with the idea of intermittent fasting in the first place. Apparently, it was used with lab rats in dietary studies going back at least to the early 1980s, and probably earlier.

Studies as far back as the 1930s demonstrated the effects of caloric restriction:

McCay, C. M., and M. F. Crowell. 1934. Prolonging the life span. Science Monthly 39:405–414

I haven’t been able to find a copy of that study on-line, but it sparked subsequent research which confirmed that some animals fed 40% to 60% of their normal diets lived as much as twice as long as those that ate normally. Almost all animals lived longer on restricted diets, though the specifics vary from one species to another.

Who it was that jumped from those findings to demonstrate that intermittent fasting could be just as beneficial, I have yet to discover. The earliest reference I have noticed so far dates from 1983:

Goodrick C. L., Ingram D. K., Reynolds M. A., Freeman J. R., and Cider N. L. (1983) Differential effects of intermittent feeding and voluntary exercise on body weight and lifespan in adult rats. J. Gerontol. 38, 36–45.

This article is also elusive on-line, though it is available for purchase. The abstract, however, is widely available, and speaks of alternate day feeding as it were nothing novel:

Effects of intermittent feeding upon growth, activity, and lifespan in rats allowed voluntary exercise.
Goodrick CL, Ingram DK, Reynolds MA, Freeman JR, Cider NL.

From weaning until death, male Wistar rats were housed in activity-wheel cages with one group maintained on an ad libitum (AL) diet and another provided the diet every-other-day (EOD). EOD-fed rats had a mean lifespan of 124 weeks compared to 103 weeks for AL-fed rats. While post-weaning body weight and growth rates were reduced among the EOD-fed animals compared to AL-fed animals, there was no significant difference in growth duration. Positive correlations were observed between lifespan and estimates of growth rate and duration in the AL group but not in the EOD group; thus, little evidence was produced to support the hypothesis that growth rate is inversely related to longevity. While the EOD feeding regimen resulted in higher activity levels later in life, wheel activity levels were actually lower in this group in early life compared to the AL group. The observation of reduced wheel activity among young rats fed EOD was replicated in a second experiment. Thus, little support was obtained for the hypothesis that increased activity mediates the beneficial effects of dietary restriction on longevity, unless this mechanism is active late in the lifespan.

Interestingly, this study only showed a 20% increase in longevity — well below the results demonstrated by some of the subsequent research.

It was not until the 1990s that humans began getting interested in trying caloric restriction. The intermittent fasting alternative doesn’t seem to have occurred to the public at large until the early 2000s, even though it was known to researchers.