Nutrition

November 24, 2013

Nutrient Timing: Don’t Let Confirmation Bias Stand in the Way of Science

Earlier this year, Alan Aragon and I published a review on the efficacy of nutrient timing with respect to enhancing muscular adaptations. The article, titled Nutrient timing revisited: is there a post-exercise anabolic window?, challenged the popular claim that nutrients must be consumed immediately after training to maximize muscular adaptations. For those who want the “consumer friendly” version of the paper, I posted a summary of findings in an earlier blog post; you can read it here.

Recently, Dr. John Ivy took issue with our findings in this review paper published in the American Journal of Lifestyle Medicine. Here is the specific passage where Dr. Ivy references our paper as well as his associated commentary attempting to refute its conclusions:

Whether there is an advantage to nutritional supplementation within the first hour after exercise has been recently challenged. It has been pointed out that the rate of protein synthesis was the same when a supplement composed of 6 g of an essential amino acid (EAA) mixture and 36 g of carbohydrate was provided either 1 or 3 hours after resistance exercise (Rasmussen et al. 2000). It was also reported by Tipton et al. that immediate pre-exercise ingestion of an EAA/carbohydrate solution resulted in a significantly greater and more sustained muscle protein synthesis response compared to its immediate postexercise ingestion. Moreover, the effect of an acute bout of exercise on muscle protein synthesis has been found to last for several days (Chesley et al. 1992; Phillips et al. 1997).

A closer evaluation of these studies, however, shows they do not refute or diminish the importance of supplementation in the first hour postexercise. For one, Fujita et al found that supplementing 1 hour before exercise with an EAA/carbohydrate supplement did not result in enhanced postexercise muscle protein synthesis. Second, Tipton et al later reported no significant difference in net muscle protein synthesis postexercise when 20 g of whey was consumed immediately before versus 1 hour postexercise. Third, when the effect of timing of nutrient supplementation on protein synthesis postexercise is evaluated, the supplement ingested closest in time to the exercise generally has the greatest impact. For example, the increases in muscle protein synthesis reported by Phillips et al at 3, 24, and 48 hours after exercise were 112%, 65%, and 34%, respectively. Finally, there are few studies that actually compare the response of supplementation immediately or within the first 45 minutes postexercise with delaying supplementation for several hours as evaluated by Okamura et al. and Levenhagen et al.. In summary, most acute exercise studies clearly support supplementation soon after exercise for optimal stimulation of protein synthesis and protein accretion.

I’ll start off by saying that I have great professional respect for Dr. Ivy. He is an esteemed professor in the Kinesiology and Health Education department at the University of Texas as well as a renowned nutritional researcher, with a long history of publications in peer-reviewed journals. What’s more, Dr. Ivy literally wrote the textbook on nutrient timing. He has been a staunch proponent of the practice for many years, and frequently lectures on its complexities. But simply because someone is considered an authority on a topic does not mean that he should be above reproach. Science is about evidence. For science to have integrity, we must be willing to challenge popular dogma and test whether it stands up to scrutiny.

In my opinion, the paper by Dr. Ivy falls far short in this regard. Instead, it comes across as a classic example of confirmation bias where evidence is cherry-picked to support a pre-determined opinion. What follows is a point-by-point rebuttal of the points made by Dr. Ivy.

1. First, Fujita et al found that supplementing 1 hour before exercise with an EAA/carbohydrate supplement did not result in enhanced postexercise muscle protein synthesis.

I’ll start with a brief summary of this study: 22 subjects performed a bout of resistance training for the lower body. One group (n=11) consumed a pre-exercise drink containing carbohydrates and protein while the other group (n=11) did not ingest nutrients prior to training. Results showed an increase in post-exercise fractional synthetic rate of ~50% with no significant differences between groups.

On the surface, these findings might seem to support Dr. Ivy’s claim that post-workout nutrition is more imporant than pre-workout nutrition. However, a closer examination reveals otherwise.

First, what Dr. Ivy conveniently failed to point out was this little nugget from the study: “However, the postexercise time course for FSR was different between the two groups in that during exercise the FSR did not decrease below basal values in the EAA + CHO group, and the postexercise increase in FSR was delayed compared with the fasting control group.” Moreover, this is but one study on the topic. Other studies have reported either similar or greater increases in protein synthesis from pre-workout protein consumption versus consuming the same nutrients post-exercise. If you are going to broach the acute response angle, it should be done in the context of the body of literature. At best, an unbiased assessment would say that evidence remains equivocal on the topic.

Perhaps more importantly, Dr. Ivy’s contention here in no way proves the existence of a narrow post-exercise window. Even if post-workout nutrition is more important than pre-workout consumption (which remains debatable), the reference provided does not indicate whether consuming nutrients within 1 hour post-workout would confer any advantages over consuming them say 3 hours post-workout.

2. Second, Tipton et al later reported no significant difference in net muscle protein synthesis postexercise when 20 g of whey was consumed immediately before versus 1 hour postexercise.

I just mentioned this study in Point 1 to counter Dr. Ivy’s claims of a narrow anabolic window of opportunity. In short, the study showed no differences between consuming 20 grams of whey either an hour before or an hour following exercise. How does this support the concept of a narrow anabolic window? If anything, it suggests no benefit to post-exercise nutrient consumption. Dr. Ivy needs to clarify his position here.

3. Third, when the effect of timing of nutrient supplementation on protein synthesis postexercise is evaluated, the supplement ingested closest in time to the exercise generally has the greatest impact. For example, the increases in muscle protein synthesis reported by Phillips et al at 3, 24, and 48 hours after exercise were 112%, 65%, and 34%, respectively.

Again, I am not clear on how the study cited here supports the concept of a narrow post-workout window? The protocol examined protein synthesis at 3, 24, and 48 hours following a bout of resistance training. The response was greater at 3 hours than at 24 or 48 hours. I am at a loss as to the relevance of these findings with respect to immediately consuming nutrients versus delaying consumption for a period of time. Perhaps I’m missing something?

4. Finally, there are few studies that actually compare the response of supplementation immediately or within the first 45 minutes postexercise with delaying supplementation for several hours as evaluated by Okamura et al. and Levenhagen et al..

It’s true that there are a paucity of studies examining the acute response to consuming protein immediately after training versus delaying consumption. My first question thus would be: Given the dearth of such research, how can Dr. Ivy claim there is such overwhelming evidence in favor of nutrient timing if this is indeed what he is using to formulate his opinion?

But let’s overlook this point and explore what research does in fact show. Here Dr. Ivy cites two studies to support his contention. The first one, by Okamura et al. investigated the response to the timed protein feeding after treadmill running in dogs. I’m going to toss this one out as pretty much irrelevant to the topic. It’s an animal study using aerobic training; not exactly indicative of the anabolic response of hard-training lifters. The other study by Levenhagen et al. was a human trial, and it did show that lower body (and whole body) protein synthesis of the legs was increased significantly more when protein was ingested immediately versus 3 hours after exercise. Problem is, the training involved moderate intensity, long duration aerobic exercise. This raises the distinct possibility that results were attributed to greater mitochondrial and/or sarcoplasmic protein fractions as opposed to synthesis of contractile elements. Let’s face it, long duration aerobic exericse is not much of a muscle-building activity. In contrast, Rasmussen et al. investigated the acute impact of protein timing after resistance training–without question a better indicator of synthesis of muscle contractile elements. In this study, no significant differences were seen in the protein synthetic response after consuming nutrients 1 versus 3 hours post-exercise.

5. In summary, most acute exercise studies clearly support supplementation soon after exercise for optimal stimulation of protein synthesis and protein accretion.

Apparently, Dr. Ivy feels he has made a compelling case to substantiate this broad, sweeping statement. As discussed herein, I think not. You be the judge.

By Dr. Ivy’s own admission, there are only a limited number of studies that have investigated the acute response to nutrient timing, and the findings of those that have endeavored to do so are discrepant. If this is indeed the basis for the nutrient timing hypothesis, it’s built on a flimsy house of cards.

Later in his review, Dr. Ivy proceeds to discuss the research looking at chronic muscular adaptations pursuant to nutrient timing. Longitudinal studies would seemingly have greater relevance to practical application, as acute measures of protein synthesis are not necessarily predictive of the long-term hypertrophic responses to resistance training. There actually are a number of studies that have investigated the temporal effects of nutrient provision on muscle hypertrophy following regimented resistive exercise. Alan and I discussed these papers in detail in our review. I won’t rehash the specifics here, but in short some studies show a benefit while others do not. Dr. Ivy curiously chose to extol the virtues of the select few that provided support to his opinion (including a study carried out in rodents and another that inexplicably found no increases in muscle mass when subjects delayed protein consumption a mere two-hours after a training bout over 12 weeks!) while harping on the limitations of those in opposition. Interestingly, he criticizes a study by Verdijk et al. (that failed to show a benefit for nutrient timing) because the dose of protein (20g) was too low while failing to levy the same criticism of a study by Esmarck et al., which showed a benefit to nutrient timing using a protein dose of only 10g! Confirmation bias?

To provide further clarity on the topic, I recently collaborated with Alan and James Krieger to conduct a meta-analysis as to the effects of protein timing on muscular adaptations. We compiled the results of 23 studies on the topic using rigid inclusion/exclusion criteria. In brief, findings showed no differences between immediate versus delayed nutrient consumption with respect to muscle strength or hypertrophy; any benefits from timing were attributed to an increased protein intake as opposed to temporal factors. The meta-analysis will be published soon in the Journal of the International Society of Sports Nutrition. I’ll have lots more to say about the study once it is available in print.

For the record, Alan and I limited the focus of Nutrient timing revisited: is there a post-exercise anabolic window? to hypertrophic adaptations. As we pointed out, there are certainly other areas where timing of meals can be a viable strategy, particularly for athletes who need to train or perform multiple times in the same day. What’s more, there is compelling evidence that resistance exercise sensitizes muscle to the anabolic effects of food. Thus, there is a benefit to consuming nutrients, and protein in particular, following a resistance training bout. The caveat is that you don’t necessarily need to worry about scarfing down nutrients the moment you finish lifting. Our findings suggest that the “window of opportunity” is probably around 4-6 hours following resistance exercise, with the specifics of timing dependent on when you ate your last meal prior to training. Delaying nutrient consumption for many hours after training would seem to be unwise.

In closing, there certainly is a need for more studies on the topic. I am open to changing my opinion should compelling evidence come to light. But based on our extensive review of literature, research supporting a narrow anabolic window is currently lacking.

If Dr. Ivy wishes to debate the topic, I welcome him to rebut my comments. I will gladly publish his response on my blog in its entirety without editing. Let’s put all the information out there so that the general public can form an educated opinion. After all, that is how science ultimately progresses and thrives.