Quite often while watching the nightly news or reading articles in general layperson publications, one will come across headlines proclaiming something along the lines of, "Drug X was found to slow down cancer progression in mice" or "Diet Y reduced cardiometabolic diseases in rats", etc. Being an inquisitive individuals, you may be asking yourself, “Do the results obtained from mice or rat studies even apply to humans?”, “What are the +’s and –‘s of animal research?” Truth is, there are many benefits to animal research. Yet, due to genetic differences, we cannot freely assume that the results seen in animals while taking a given supplement, diet, or exercise protocol will necessarily translate over to humans. Thus, animal based research should be viewed as a foundation for what may be worth examining in future human based trials.
Animal Studies and Popular Media
Figure 1. A lab mouse. Photo Source7
(PLEASE NOTE: Any time I refer to “animal studies” in this article, I’m actuality referring to “non-human studies.”)
Quite often, while watching the news, reading general layperson publications, etc, I’ll come across headlines such as "Breakthrough Research: Product X Increases Testosterone Levels …", "Researchers show that compound Y protects against Heart Disease. " or "Want to speed up fat loss? Science indicates that by adding ingredient Z to our diet…" Like any health and performance conscious individual, I will often read/listen to what they have to say. Half the time, upon looking a little deeper into the news brief, I’ll find one key fact that was left out of the headline —> The research was completed on animals. Furthermore, this key fact is often glazed over pretty quick as the news piece tends to highlight the potentially positive effects that the compound/variable of interest may have on humans. I’m sure that you’ve found yourself in a similar situation on numerous occasions. Being of inquisitive nature, you may find yourself asking, “Why was this study done in animals rather than humans?”, “Should we even care?” or “Can we expect to see similar results in humans?” In other words, "How should we interpret animal research?"
Benefits of Animal Research
(Please note, when I say “benefits of animal research”, I am referring to this in PURELY scientific terms. This is NOT intended to be a discussion on if it’s ethical or moral to perform studies on animals. That is for you to decide based on your personal belief system.)
No Harm to Human Health
From a scientific perspective, there are many advantages to running studies with animals vs. humans. The most obvious benefit is that animal studies allow researchers to study a physiological mechanism without the risk of harming humans. For instance, scientists often genetically manipulate mice such that they’re predisposed to develop various cardiometabolic diseases (I refer you to the “animal studies” section of Part I of my article on dietary AGEs for examples). Similarly, if scientist want to find out if substances “X”, “Y”, or “Z” influences cancer development or progression, they're going to use animal models as the basis of the research. In doing so, they learn more about the disease process without the risk of hurting humans.
Reducing Confounding Factors
Another advantage of animal studies is that it’s easier to prevent confounding variables from influencing the results of the study. Let’s take a hypothetical study in which we’re investigating the long term effects (i.e. 3-12+ months) of a given diet on cardiometabolic diseases. If we’re using animals as test subjects, we control their food exposure 100%. In contrast, humans may follow the prescribed diet 90%, 80%, or 70% of the time over the course of the study. Even if they do follow the diet 100% (which in reality doesn’t happen), differences in their lifestyle can throw other confounding factors into the equation. This includes living conditions (vs. mice which all live in similar cages, held at similar temperatures, etc), stresses that may be going on in their life, activity levels, etc. Although specific statistical tests, accounting for these differences can be run, it’s never as good as if the confounding factors weren’t present in the first place.
Truly Assessing Long Term Effects
It’s also much easier to assess the long term effects of manipulating a given variable over the course of one’s lifespan in animals vs. humans. For instance, the average lifespan of mice is 1.5-3 years1. Thus, using the diet-cardiometabolic disease example from above, a 12 month study represents tells us the effects of how eating a specific way for ~1/3 to ~2/3 of their life affects disease outcomes. On the flip side of the equation, this same 12 month window only covers 1/70th of the lifespan in humans (using a life expectancy of 70 years). As you can see, this makes it much harder to assess the effects of a certain diet when, in all actuality, the “long term human study” only represents a minute fraction of an individual’s life.
The Economy Stupid
The final beneficial factor of running animal studies is what I like to call the Bill Clinton principle known as “The Economy Stupid.” (For those who do not follow American politics, former US President Bill Clinton used this as a campaign slogan during his successful 1992 presidential campaign). More or less, animal studies are cheaper to run than human studies. Think about it; let’s say that researchers are assessing the effects of following Diet A vs. Diet B for 2 weeks. Meals and snacks are to be provided for each participant. Using this study design, is it going to be more expensive to feed humans or mice/rats over this time span?
Downside of Animal Studies
From a scientific viewpoint, there is one “little” problem with freely applying animal research to humans…. WE ARE NOT MICE/RATS!!! Due to genetic differences, we cannot freely assume that the results seen in animals while taking a given supplement, diet, or exercise protocol will necessarily translate over to humans. At times the results match up relatively close between species. Yet, as seen in the 2 examples that follow, discrepancies may arise dependent upon the population being studied.
Example 1: Vitamin C
Figure 2. The conversion of glucose to vitamin C. Image 1 = Glucose, Image 6 = Ascorbic Acid. Please note that the glucose molecule presented above is in its open chain form (Fisher Projection). In the body, glucose is actually in a closed ring structure. However, this was the best picture that I had free access to that showed the pathways. Photo Source8.
I’ll let you in on a little known fact… Vitamin C is not required in the human diet. What, you don’t believe me? Well, it’s been proven beyond a reasonable doubt that vitamin C is not required in the diet of mice or rats.2 Since mice and rats don’t need it, surely we don’t need it! Ok, ok, maybe I’m partially pulling your chain. Vitamin C is required in the human diet. However, it is true that mice, rats, and most other animals for that matters do not require vitamin C in their diet as they can convert glucose into vitamin C (See Figure 2). For better or for worse, we lack the key enzymes that are responsible for this process.
Example 2: Creatine
Do not take creatine because it will not be absorbed into your muscles. What, you don’t believe me? Well, in a study conducted by Sewell and Harris, 4 horses were given a human equivalent dose of 0.35-0.45g/kg creatine over the course of 13 days.3 (I have a range for this as I only had access to the abstract of the journal article. Thus, I could not see the actual “size” of the horses, which plays a role in equating the human equivalent doses. Thus the figures I used were based off the respective Km’s of both a large and small horse which were 110 and 87.5 respectively4. If you’re confused with what I’m referring to, please skip down to the Human Equivalent Dose Section). At the end of the study, it was observed that creatine monohydrate supplementation did not increase total muscle creatine content in horses.
If we blindly accepted the results of this animal based study, we’d conclude that creatine supplementation is unable to increase the creatine content of our muscles. However, this is NOT the case. Creatine monohydrate supplementation has routinely been shown to increase muscle stores (10-40%), leading to enhanced physical performance.56
Animal Studies – Should we Pay Attention?
Now that I’ve laid out the + ’s and the –‘s of animal studies, we’re back at the main question… Animal Studies – Should we pay attention? My recommendation – Be aware of them but don’t “jump the gun” and assume their results will necessarily translate perfectly over to humans. Animal studies should serve as the foundation upon which future human based trials can be based off. I’ve always thought of animal studies as “back pocket ideas”. In other words, when I hear about interesting results from animal based studies, I’ll make a mental note of the findings, tuck it into the back of my mind, and wait to see if human studies refute or concur with it before I make any major changes into my lifestyle. (Please note that this is a general statement. If I come across a study showing that substance “X” causes cancer or similar in animals, I’d be much quicker in incorporating this information into my daily routine).
The other part where I strongly recommend “being aware of animal research” is when purchasing supplements. In my opinion, supplement companies are generally the WORST OFFENDERS of abusing the results of animal studies. As mentioned in the intro, when reporting the news, most reporters tend to de-emphasize the fact that the research of note was conducted in animals. In the case of supplement manufactures many go BEYOND de-emphasizing this fact and COMPLETELY FAIL to mention that the studies supporting their claims were done on animals. Usually you’ll just see claims along the lines of:
"Scientifically proven to increase testosterone levels, muscle growth, aerobic/anaerobic capacity, etc, etc"
If you see a claim like this, try hard to find out if the study was completed on humans or animals. Do not let supplement companies trick you into assuming that the results were found in humans. If they fail directly list the references to support their claim(s), look at the ingredients list and put to use the skills you learned while reading the articles in the Consumer Savvy section of this website.
Human Equivalent Doses (HED)
There is one topic related to translating results from animal studies to human studies that I briefly want to discuss. One of the biggest errors that reporters, online gurus, etc, make when interpreting research is that they fail to properly translate the animal supplemental dose into the human supplemental dose; this is not a simple 1:1 ratio. For instance, let’s say that in an animal study, rats receive supplemental plant extract “X” in the amount of 500 mg/kg of body weight. After 4 weeks, researchers observed that taking “X” significantly improved health/performance outcomes vs. the control group. Seeing these results, our resident “guru” goes out and proclaims:
"If you want to receive the health benefits of substance “X” you need to eat 500 mg/kg of bodyweight. "
I want to inform you that this is WRONG. Different species have different metabolic rates. As a result, we have to account for these differences by calculating human equivalent doses (HED)10.
To calculate the HED for studies using RATS, use the following equation:
HED = (animal dose)(0.162)
To calculate the HED for studies using MICE, use the following equation:
HED = (animal dose)(0.081)
Please be aware that HED are only estimations. I must also mention that I am quickly glossing over the use and logic of using human equivalent doses. I STRONGLY RECOMMEND you checking out an article, written by my friend Dr. Moussa, over at SuppVersity entitled What Are Human Equivalent Doses (HED) and How Do I Calculate Them?. Even if you aren’t interested in finding out more about HED, I still encourage you to check out his SuppVersity website – it’s one of my personal favorites!.
Bottom Line
As I’ve laid out in this article, there are many benefits and drawbacks to using animal studies. At times the results of some studies may translate well over to humans; yet, in other instances a little factor known as “genetics” throws a wicked curveball into the equation. Thus, animal based research should be viewed as a foundation for future human based trials. Once we have thoroughly done our “Re”-search, we can take the information, do a little “Me”-search and truly determine if the results of a study apply to our health/performance goals.
References
1 Biomethodology of the Mouse – Animal Research. Institutional Animal Care and Use Committee. University of Iowa. Accessed August 18, 2011 from: http://research.uiowa.edu/animal/?get=mouse&PassToURL=%22mouse%22
2 Wardlaw GM, Hampl JS, DiSilvestro RA. Perspectives in Nutrition. 6 ed. Pg 353.
3 Sewell DA, Harris RC (2002) Effect of creatine supplementation in
the thoroughbred horse. Equine Vet J 18:239–242
4 Morris TH. Antibiotic therapeutics in laboratory animals. Laboratory Animals (1995) 29, 16-36. Accessed August 21, 2011 from: http://la.rsmjournals.com/cgi/reprint/29/1/16.pdf
5 Buford TW, Kreider RB, Stout JR, Greenwood M, Campbell B, Spano M, Ziegenfuss T, Lopez H, Landis J, Antonio J. International Society of Sports Nutrition position stand: creatine supplementation and exercise. J Int Soc Sports Nutr. 2007 Aug 30;4:6.
6 Jäger R, Purpura M, Shao A, Inoue T, Kreider RB. Analysis of the efficacy, safety, and regulatory status of novel forms of creatine. Amino Acids. 2011 May;40(5):1369-83. Epub 2011 Mar 22.
7 Image created by Rama. This file is licensed under the Creative Commons Attribution-Share Alike 2.0 France license. Accessed August 18, 2011 from: http://commons.wikimedia.org/wiki/File:Lab_mouse_mg_3263.jpg
8 Image created by Yikrazuul and placed in the Public Domain. Accessed August 18, 2011 from: http://en.wikipedia.org/wiki/File:Synthesis_ascorbic_acid.svg
9 Image taken by Nicolas Kaiser. This file is licensed under the Creative Commons Attribution-Share Alike 2.0 Generic license. Accessed August 21, 2011 from: http://commons.wikimedia.org/wiki/File:Liquid_filled_compass.jpg
10 U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER). Guidance for Industry Estimating the Maximum Safe Starting Dose in Initial Clinical Trials for Therapeutics in Adult Healthy Volunteers. July 2005. Accessed Aug 22, 2011 from: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm078932.pdf