More on intermittent fasting

I would like to thank George Albaugh for calling my attention to two studies from Heilbronn et al. ("Alternate-day fasting in nonobese subjects: effects on body weight, body composition, and energy metabolism" Am J Clin Nutr. 2005, 81:69-73.[PubMed]. and "Glucose tolerance and skeletal muscle gene expression in response to alternate day fasting;" Obes Res. 2005, 13:574-81 [PubMed]). These papers describe the effect of a single brief period (3 weeks) of intermittent fasting. I was heartened to see that SIRT1 expression (measured by RT-PCR on muscle biopsies) does indeed increase (p = 0.01), although the effect is relatively small. But I was also concerned to see a possible adverse effect on glucose tolerance.

However, there are reasons why this study may not be directly applicable to my case. They describe a "24 hour" fast, from midnight to midnight, with no mention of how this rule was followed. If I were to follow those instructions I would almost certainly eat at least some food right around midnight each day (just before or just after, depending on whether I was beginning or ending a fast)! This would be similar to the diet I follow now, being a 24 h. fast, except that my large meal is at dinnertime and my average length of fast is probably about 23 hours rather than a full 24. Two things about this concern me. One is that food eaten immediately prior to sleeping may not be digested as well. The other is that the food I eat at midnight, if I do eat at midnight, is Häagen-Dazs Vanilla Swiss Almond or Chocolate Chocolate Chip ice cream. Everyone is different, but social and practical factors might lead those eating at midnight to include a higher proportion of prepared foods in their diets.

The alternative way of following the midnight-to-midnight rule would be to fast from going to bed to waking up. This is much different. A 32 hour fast is only a third longer than a 24 hour fast (perhaps as much as 40% longer than what I'm doing), but probably doubles or triples the time spent hungry, which is presumably the relevant variable for inducing physiological responses. I would find this diet, which is closer to what George is doing, to be significantly harder to follow (especially the bit where I have to go to sleep hungry). In fact, the article in the American Journal of Clinical Nutrition concludes that "Hunger on fasting days did not habituate over the course of the study, which perhaps indicates the unlikelihood of subjects continuing on this diet for extended periods of time." In contrast, what I'm doing now is something that I know I can keep up indefinitely, and that is a big advantage.

So, my concern is that this study had people following two different protocols. My intuition is that men are more likely than women to follow the midnight snack protocol, and more likely to eat high-calorie foods when they do. This could explain some of the differences observed. My advice to the authors of these studies would be to test one protocol or the other. If a one-day diet like the one I'm on is desired, then the instruction could be to fast for at least 22 hours from dinner to dinner (leaving it up to the individual to choose meal time). On the other hand, if the full-day diet is desired, then the instruction could be no food from 4 am to 4 am and to fast for at least 30 hours. Apparently, that was their intent. I have exchanged email with Eric Ravussin (the senior author), who says that most subjects had fast times of about 30 hours, but I wonder if they have interview data that would allow them to sort out what people actually did. The effectiveness of a shorter fast is of obvious interest to me, and I wonder if their existing data bears on this.

In any case, it's exciting that this research is being done, and heartening that they are seeing an effect on SIRT1 expression.

Yahoo! group on intermittent fasting

I just created a new group on Yahoo! This group, which is simply "fasting," is devoted to intermittent fasting and its effects on physiology and health. I expect that both practitioners of intermittent fasting and scientists with an interest in the physiological effects of intermittent fasting will want to join. The founding members are both practitioners and scientists. We are interested in the idea that intermittent fasting may be a preferable way of obtaining the health benefits associated with caloric restriction (see my post on this topic). Although we are interested in many aspects of fasting, including styles, effects and reasons to fast, this group is not specifically about weight loss, colonics, the purging of toxins or the attainment of spiritual goals.

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Intermittent Fasting

It has been known for a long time that caloric restriction (a significant reduction in food intake – to 60-70% of normal levels) prolongs life,and improves health in many species (even including yeast!). Many people are interested in caloric restriction (for example, a caloric restriction support group on Yahoo! has 1,687 members) but relatively few people are willing to actually follow such an extreme diet. However, evidence that the benefits of caloric restriction result from the activation of a genetic program (involving insulin signaling and the gene SIRT1) rather than reduced metabolic activity per se has opened up the possibility that benefits can be achieved by other means. The current issue of Cell (February 25, 2005) is devoted to reviews on aging and includes an article by Lenny Guarente (PubMed) that makes this point in particular. One hope is finding a drug or dietary supplement that will do the job (perhaps resveratrol). I have paid more attention to the possibility that the same genetic program may be induced by intermittent fasting.

At the beginning of May last year (2004) I started a diet that involves not eating on Mondays, Wednesdays and Fridays. My diet was inspired in particular by a study (Anson et al., 2003) that reported beneficial effects on glucose metabolism and neuronal resistance to injury without an overall reduction in calorie intake. In this study, mice were assigned to four groups (ad libitum, intermittent fasting, caloric restriction and pair fed; this last group was given as much food as the intermittent fasting group ate, but on a daily basis). The intermittent fasting group did as well as the caloric restriction group on a variety of tests but enjoyed almost as much food as the ad libitum group (by making up the difference on days when food was available). A very recent paper by Hsieh et al. 2005 (Effects of Caloric Restriction on Cell Proliferation in Several Tissues in Mice: Role of Intermittent Feeding: PubMed; Am J Physiol Endocrinol Metab) reaches similar conclusions studying cell proliferation.

I fast between dinner of one day and dinner the next day, but eat dinner every day. The fast consists of no calories at all (I allow myself water, tea and coffee), and the precise duration depends on when we have dinner, according to the details of each day's schedule. While I normally fast three times each week, I am flexible. For example, I might allow myself to schedule lunch on a Friday after having fasted on Monday and Wednesday. In fact, I've done this only a few times since starting the diet. One week I postponed Friday's fast so that I fasted on Monday, Wednesday and Saturday that week.

The health benefits of intermittent fasting in humans are certainly not established, and I'm not recommending this diet for anyone else. I find it likely that caloric restriction works in humans because it works in so many other species. However, it is possible that the genetic program is already constitutive in humans. It is also possible that the particular diet I have selected fails to induce the pathway. Perhaps longer but less frequent fasts would be more effective, or many fewer fasts would be sufficient. I don't know, but I am encouraged by the growing evidence that the induction of extreme longevity can be uncoupled from caloric restriction per se.

I don't find this diet to be terribly difficult. In fact, skipping meals can be convenient (I'm busy, after all). For about three weeks after starting the diet I would experience mild hypoglycemic symptoms on the fast days (I was nervous but tired, just a little irritable and not terribly productive) and became sleepy when I ate again. These symptoms have passed. I now feel pretty much the same on fast days and other days. This diet is not about losing weight. I lost about 10 pounds over the first six weeks and then stabilized (and I am starting to gain some of this back). There are side effects. In particular, I don't think that it's a good thing to routinely drink strong coffee on an empty stomach (which is what I'm doing three days each week). I am aware that this diet is the opposite of the standard "healthy eating" advice that advocates a big breakfast and regular meals, and I must confess that I have passed up opportunities to discuss it with my doctor (although I have mentioned it to friends who are doctors). On the other hand, fasts of various kinds are a part of almost all religious traditions. I suspect that a study with direct tests of the relevant biomarkers (reduced serum glucose and insulin levels, or even elevated expression of SIRT) is possible, and will eventually be carried out, but I've decided not to wait for it. In the meantime, I can only quote the endorsement of my friend Peter Roemer, who was responding to an article in "The Economist", (March 31, 2005: "Even a slight decrease in calories may lead to longer lifespans") about the Hsieh et al. article cited above:

"OK, I'm giving it a try. Of course, this is exactly what Steve has been doing for a while. And look, he's still living!!!"

This also appears on SteveMount.com as Posting 2.