The Dark Side of Protein Supplementation: Study Pinpoints Effects on the Microbiome

Protein supplements, which come in many different forms, ranging from powders to bars to ready-made drinks, are high on the list of the most popular nutritional products on the market today. As a result of widespread promotional offensives spearheaded by athletes and fitness bellwethers who’ve struck lucrative endorsement deals, it’s become fairly common – not just among gym junkies, but also among average Joes and Janes – to have a bucket of protein powder in one’s kitchen cabinet, which represents a convenient way of elevating the amino acid content of smoothies, meals, and post-workout shakes.

Many use protein supplements in the belief that doing so will enhance not only their workout results, body composition, and overall physique, but also their general health; an idea that’s emphasized and nurtured by all of the focus that’s devoted to the importance of protein for appetite regulation, bone density, and muscle maintenance. This aspect of dietary protein has been simplified and inflated to such an extent that it’s largely overshadowed the fact that not all forms of protein agree with the human biology…

The adverse effects of protein supplementation

In the past, I’ve talked at length about the problems with protein supplements here on the site, focusing particularly on whey protein, which represents the leading type of protein on the market today. As part of those discussions, I’ve highlighted the fact that the research that’s been brought up in support of the idea that protein supplementation is beneficial has several inherent limitations to it, the most prominent of which is that most of the studies that have been conducted to date fail to account for certain important biological considerations and haven’t matched the protein intake of the placebo group with that of the intervention group, something that curtails the significance of the findings.

The key point I’ve tried to get across is that protein supplements (e.g., whey protein powder) are evolutionarily novel additions to the human dietary repertoire that have a configuration that looks nothing like that of any of the foods we’re evolutionarily accustomed to consuming. Hence, from a Darwinian point of view, one would naturally expect that there are problems associated with the use of such products.

A growing body of research supports this Darwinian nutritional position, some of which I’ve brought up in the past. Among other things, I’ve pointed out that whey protein is insulinogenic and acnegenic (1, 2, 3, 4) (Actually, it’s been shown to have a more potent effect on insulin secretion than some high-carbohydrate foods). More recently, I devoted an entire post to the problems with casein, another common type of protein utilized in supplements, and shared a new study linking an elevated intake of branched-chain amino acids with central serotonin depletion and hyperphagia, supporting the idea that it’s better to take in a variety of amino acids as part of whole foods than to ingest isolated amino acids as part of supplements.

While problematic in themselves, these effects aren’t what cause me the most concern. Rather, ‘what keeps me up at night’ is my conviction that protein supplementation, and in particular whey protein supplementation, adversely affects gut microbiota stability and composition, thereby potentially undermining everything from immunity to cardiovascular health to cognition. I’ve talked about this notion, which is based on my experience and understanding of nutrition and human-microbe interactions, in the past, pointing out that milk proteins would be expected to support an infant-like microbiota, which would help explain their purportedly beneficial effects on intestinal barrier function.

A study published last year in the open access journal Nutrients adds support to this idea…

The study

Here’s the gist of the study, which is entitled Effect of a Protein Supplement on the Gut Microbiota of Endurance Athletes: A Randomized, Controlled, Double-Blind Pilot Study…

Abstract: Nutritional supplements are popular among athletes to improve performance and physical recovery. Protein supplements fulfill this function by improving performance and increasing muscle mass; however, their effect on other organs or systems is less well known. Diet alterations can induce gut microbiota imbalance, with beneficial or deleterious consequences for the host. To test this, we performed a randomized pilot study in cross-country runners whose diets were complemented with a protein supplement (whey isolate and beef hydrolysate) (n = 12) or maltodextrin (control) (n = 12) for 10 weeks. Microbiota, water content, pH, ammonia, and short-chain fatty acids (SCFAs) were analyzed in fecal samples, whereas malondialdehyde levels (oxidative stress marker) were determined in plasma and urine. Fecal pH, water content, ammonia, and SCFA concentrations did not change, indicating that protein supplementation did not increase the presence of these fermentation-derived metabolites. Similarly, it had no impact on plasma or urine malondialdehyde levels; however, it increased the abundance of the Bacteroidetes phylum and decreased the presence of health-related taxa including Roseburia, Blautia, and Bifidobacterium longum. Thus, long-term protein supplementation may have a negative impact on gut microbiota. Further research is needed to establish the impact of protein supplements on gut microbiota.

As you can gather from the abstract, the investigators found that supplementation with a mix of whey isolate and beef hydrolysate for 10 weeks decreased the levels of certain types of gut bacteria that have previously been linked with favorable health profiles. Of note, this change occurred even though the participants only took in 20 grams of added protein per day, which is by no means a supernormal intake.

Caveats

While noteworthy, the results of the study should be interpreted in light of its small sample size. Also, it’s important to recognize that the two study groups weren’t matched with respects to total protein intake. Hence, one can’t exclude the possibility that the observed effects were either fully or partly due to a general elevation of protein consumption, as opposed to the use of a protein supplement per se.

Furthermore, as I’ve pointed out in the past, I’m somewhat hesitant about drawing conclusions about health and disease off of gut microbiota analyses, as no exact standard as to what constitutes a healthy microbiota exists. There’s invariably going to be much inter-individual variation, even among healthy folks; hence, as I see it, it’s foolish to rely exclusively on gut microbiota profiling as a means of health assessment. With that being said, certain characteristics are representative of healthy states, meaning that the outcome of gut microbiota analyses may be indicative/suggestive in terms of host health.

The idea that gut microbiota profiling only gets us so far is strengthened by the fact that microbiome studies often seem to conflict with respect to their findings, at least at first glance. For example, the conclusions reached by the authors of a 2017 study on whey protein come across as being at odds with those of the authors of the study I’ve brought up in this article (5). I don’t put as much weight on that study as I do on this one though, as it was conducted in vitro.

What all of this is to say is that research in the absence of Darwinian insights doesn’t get us very far, and that additional studies would be required to fully elucidate the effects of different types of protein supplements on gut microbiota composition. Ideally, such future studies would in addition to gut microbiota analyses include thorough assessments of the participants’ health.

Primary takeaways

Protein supplementation may be convenient; however, it’s also problematic, in the sense that it’s an evolutionarily novel practice that may adversely affect several aspects of health. This has largely gone unnoticed, much due to the widespread focus on the importance of adequate protein consumption, as well as the non-Darwinian and business/money-driven nature of 21^st century bodybuilding and fitness. To date, most of the research has been focused on whey protein, which adverse effects are likely mediated, to some extent, by gut bacteria, as supported by a fairly recent study linking consumption of isolated whey and beef protein with gut microbiota distortions. Hopefully, such research can help draw attention to the dark side of protein supplementation.