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marylin monroe
Showing posts with label educate yourself. Show all posts
Showing posts with label educate yourself. Show all posts

Ask Dr. Andro: "Does Adding Milk to My Tea Reduce Its Health Benefits or Destroy the Antioxidants? Is There a Difference For Black, Green and White Tea?"

Image 1: Monkey milk tea by Conchibi. No matter how decorative it may look, according to various online sources, the milky monkey decoration is just about to annihilate the beneficial health effects of tea at the very moment it mingles with the antioxidant brew... or is this just another urban myth that is reaffirmed by 'gurus' all over the Internet?
Question from Samir Banga (via Facebook): "Just wanted to ask you about tea and if adding milk or cream for that matter disturbs or destroys the antioxidants/good stuff in the tea. Also would this be the same with black, green and white tea?"

Answer Dr. Andro: This is one of the typical cases where just typing in a question in Google produces either answer A "tea with milk = no problem" or answer B "tea with milk = worthless swill" - it just depends on how you formulate the question - or maybe who on whether the milk industry advertises with Google? Who knows.... A more thorough investigation, on the other hand, turns up a whole host of studies, the results of which are similarly conflictive. So what can we do to find out the truth? Well, we will do our very own little meta review. Sounds pretty sophisticated, doesn't it? Certainly something only Dr. Andro can do. Well, not really... take my virtual hand and I will show you that, oftentimes, you can easily answer your questions yourself, if you mix PubMed, Excel and some of your own gray matter and simmer that for a few hours.

First we will have to find some real data related to the question

To "google" the answer would be a highly unreliable undertaking. Too many self-proclaimed experts (like me) run fancy looking blogs (like the SuppVersity) where they propagate factoids - something you will of course never find on the SuppVersity ;-) Our first task is thus to find real data, a process that obviously requires
  1. to know what real data is
  2. to know where to find this real data
  3. to know how to find this real data
  4. to have access to this real data
The latter, I assume could unfortunately pose an insurmountable hurdle for some of you, because even scientists, or rather the editors and publishers of the magazines the scientists publish their articles in, need to pay for their tea and milk and tend to charge horrendous sums for a single article (I have seen individual physics papers for >199$), if you do not  have access to the respective journals from a university or public library. So, in case you cannot follow all my next steps minutely do not fret, the number of freely accessible articles is ever increasing and I promise that you will get the answer to Samir's question and even more for free ;-)

'Pubmeding' is 'googling' for smart people

Image 2: By using search tokens, we
were able to limit the no. of results to
138, a simple search for "milk in tea"
would have produced 503 hits and
good (?) old google would have spit
out roughly 96.500.000 predominant-
ly irrelevant if not corrupted results
First thing we will do is go to the medical database of the US National Library of Medicine (www.pubmed.com) - and though I think that much of the dietary advice coming from the US National Institute of Health does more harm than good, the PubMed database comprises almost all medical papers that were published in any serious journal (not only the prestigious ones) from the realms of medicine, exercise, nutrition and beyond. On the PubMed website, we will  type in the following search term "milk AND (coffee OR tea) AND (antioxidant OR polyphenol OR vitamin OR health)". It goes without saying that this will deliver all articles which deal with milk in relation to coffee or tea and their antioxidant, polyphenol, vitamin and caffeine content, as well as diverse health effects. 
Note: You may have noticed that, out of personal curiosity, I have expanded our complex search term beyond Samir's original question to another often overlooked yet similarly healthy caffeinated beverage, of which the average American drinks 3.1 cups each day - coffee! And since I have heard rumors that milk could also influence the pharmacodynamics, i.e. the absorption and effect, of caffeine, when it is added to caffeinated beverages, I also included the term "caffeine" in our complex request. Notwithstanding the complexity of the latter, the use of multiple key words and tokens for their logical connection limits the number of "hits", i.e. studies that match our criteria to 503 (cf. image 1).
From the initial 503 published articles the database has to offer, those papers which actually have our keywords in their title are obviously most likely to contain the information we are looking for. A mouse-click on the "see more" link below the "titles with your search terms" heading in the right column of the webpage (highlighted in image 2) reduces the results by -99.4% and leaves a manageable amount of three studies for us to 'review':
Illustration 1: The way to a manageable
amount of reliable data for a meta-analysis
1: Ryan L, Petit S. Addition of whole, semiskimmed, and skimmed bovine milk reduces the total antioxidant capacity of black tea. Nutr Res. 2010 Jan;30(1):14-20. PubMed PMID: 20116655.

2: Reddy VC, Vidya Sagar GV, Sreeramulu D, Venu L, Raghunath M. Addition of milk does not alter the antioxidant activity of black tea. Ann Nutr Metab. 2005 May-Jun;49(3):189-95. Epub 2005 Jul 13. PubMed PMID: 16020939.

3: Leenen R, Roodenburg AJ, Tijburg LB, Wiseman SA. A single dose of tea with or without milk increases plasma antioxidant activity in humans. Eur J Clin Nutr. 2000 Jan;54(1):87-92. PubMed PMID: 10694777.
And, lo and behold, all three are actually relevant to the question we want to answer! Heureka! Our initial euphoria begins to fade, however, when we have a closer look at the titles. While the most recent study (Ryan. 2010) claims that the addition of milk reduces the total antioxidant capacity of black tea, Reddy et al. (Reddy. 2005) and Leenen et al. (Leenen. 2000) in their studies, five and ten years before, found no reduction in the antioxidant activity of (black) tea.... well, I guess the question would not have been worth being included in the famous *hem* Ask Dr. Andro column if typing in a few words into a search engine would have delivered the correct answer right away*.
* We will have to postpone the effects on caffeine absorbtion and differences between the effects of milk in coffee vs. tea on another Ask Dr. Andro column, though, because the titles of our search results suggest that there won't be any information on these secondary issues in the respective fulltexts.

Its good not to have to rely
on pubmed for the links to
the fulltexts of papers you
are interested in; learn how
to find the FTs right at the
source, the webpage of the
respective journal
How to find a full text, if pubmed does not link to it? Usually the pubmed guys make it pretty easy for you to find the fulltexts to the studies their database contains. Normally, a single click on a button-like image of the logo of the respective publisher in the upper right corner of the pubmed sub-page with the abstract suffices, yet from time to time, the guy who fed the abstract into the database was to lazy to provide a link... and guess what, in  case of the Leenen study, the button is missing. From the cryptic abbreviation  "Eur J Clin Nutr. 2000 Jan;54(1):87-92" that is given in the line right above the title of the article and in the bibliographical information I provided, you do yet know that the paper has been published in 2000 in the 54th volume, 1st issue of the European Journal of Clinical Nutrition. Now, google will tell you that the "archive of " can be found at http://www.nature.com/ejcn/archive/index.html, and a few clicks later (year 2000 > volume 54 no. 1) you can download the study as PDF document, et voila!

Diging into it: Understanding the research design

Since we already know that the antioxidants in tea are good for us - otherwise we would hardly be worried that the addition of milk could "disturb or destroy" them, as Samir put it - the synopsis of the research, an obligatory part of the introduction to any scientific paper, which, in the case of the Ryan paper, focuses on the health benefits of tea and the tea consumption of the average UK citizen, is not really of interest to us. What is of utmost importance, though, is the research hypothesis, which is usually stated at the end of the introduction. Here, Ryan & Petit state three concrete objectives, which are...
  1. To analyze and compare the antioxidant capacity of five brands of commercially available tea
  2. To determine the effect of infusion time on the antioxidant capacity 
  3. To examine the effect of different volumes of bovine milk (10, 15, and 20 mL) and milk of varying fat content (whole, semiskimmed, and skimmed) on the total antioxidant capacity of the 5 teas
In essence, only objective #3 is relevant in the context of the question at hand; yet, knowing how to vary infusion times to maximize the antioxidant content of our tea, in the first place, would certainly be a nice bonus.

Next, we are going to collect relevant information on the actual experimental procedure
  • the tea was bought at a conventional supermarket
  • content of the tea bags varied slightly (2.7-3.3g) between the 5 commercial brands
  • 200ml of 90° hot water were used for infusion
  • 6 infusions for all 6 infusion-times (1, 2, 3, 4, 5 and 10 min); thus 36 individual samples for each brand
  • individual analysis of concentration effect of squeezing (10s right after removal) the tea bag after 1, 2, 4 and 8min of brewing; another 24 samples for each brand
  • addition of 10, 15 and 20ml whole, skimmed and semi-skimmed milk (after cooling the sample by infusion of the same amount of cool water); another 54 samples for each brand
  • technique used to analyze the 570 samples: ferric iron reducing antioxidant power (FRAP) assay
Now, the penultimate of these 7 points should make you wonder, whether this would not distort the results, because adding milk to a previously diluted tea would of course produce reduced antioxidant values compared to an undiluted version without milk. Ryan & Petit were however conscious of this problem and used accordingly diluted samples as their references, which increased the number of samples the scientists had to analyze to 588.

Finding and analyzing the relevant data

While obviously, the major results of this large scale investigation can be found in the text, the tables and figures the authors provide are of even greater value to independent thinkers like us. Using some sort of spreadsheet software we make good use of the 'raw' data on the influence of infusion times on the FRAP concentration of the freshly brewed tea. Instead of relying on the confusingly overcrowded and not very informative figure the authors provide, we create our own figure (figure 1) which comprises the FRAP values of tea 1 (median FRAP) and tea 2 (maximal FRAP) after 1, 2, 3, 4, 5 and 10min brewing with and without a tea bag. In that, we go beyond the simple graph Ryan and Petit had to offer, and bring to light how meaningful the negative effect of the tea bag in terms of the total antioxidant concentration of the brew actually is.
Figure 1: Although authors usually provide you with graphical illustrations of their data, it is often worth-wile to plot your own graphs from the data they provide, to illustrate and understand things the authors may have considered ir-/less relevant and have thus not included in their graphical analysis - in this case this would be the effect of the tea bag, which is missing from figure 1 in the original study by Ryan & Petit (data from Ryan. 2010)
If we now have a look at our fancy graph, we will immediately notice that convenience, as so often, takes it toll:
Just because we are too lazy to tinker with the loose tea leafs we give away somewhere between 50% and 5% of the total antioxidant capacity (depending on the brand and infusion time of the tea).
In that, it is interesting to note that the overall effect appears to be much greater with Tea 1 - as it can be seen in figure 1, the FRAP values of teas 1 and 2 are almost identical, if they are removed from the tea bag before infusion, which suggests that the quality of the teabag is an unexpected, yet important factor, when it comes to brewing an antioxidant rich tea. Altogether, these observations tell us that the use of teabags is generally not advisable, if you do not like the bitter taste long-infused teas tend to develop.

Doing some basic math to be able to estimate effect sizes

As interesting (and surprising) as they may be, the insights on the effects of tea bags on the amount of antioxidants are not really relevant for our personal research question, which relates to the effect of milk on the antioxidant activity of tea. Now, before we even bother with the data analysis, imagine, we did not even have data on the antioxidant activity of the tea + milk mixture. In that case, the only, yet questionable way to decide whether the addition of milk reduces the anti-oxidant value of tea would be to analyze the antioxidant value of milk, which is something Ryan & Petit actually did, and do some basic volume-based calculations.

Ryan & Petit found that fresh whole milk, semi-skimmed and skimmed milk had about 68%, 66% and 60% of the maximal FRAP value of (unbagged) tea and that these values declined by roughly 37.5% and 13.75% after 7 and 14days, respectively. Now, if we add a liquid with a FRAP value of say 5000µmol/L (fresh whole milk) to a brew of tea with a frap value of >8000µmol/L (Tea 1, leafs only) we will obviously reduce the total antioxidant level of the mixture. If we simply assume that the pre-cooled tea (20ml cold water added) has a FRAP value of 8000µmol/L (the exact reduction due to the addition of water would only matter, if the author had not used the 'cooled' specimen as reference, anyway), the addition of another 20ml of whole milk with a FRAP of 5000µmol/L would create a 11:1 mixture of high vs. low FRAP liquids, which would then have a FRAP value of 7.750µmol/L, which would obviously be a -3.125% reduction in the total antioxidant capacity of our tea by the addition of whole milk.

The smart SuppVersity teacher and students that we are, we are without doubt aware that this basic calculation oversimplifies our "problem". Yet, imagine the scientists found that the addition of 20ml of whole milk did in fact reduce the FRAP value by no more than -3.125%. In that case, we would have a reduction, but that reduction would be meaningless in view of our research question, because overall you would even get more antioxidants from your 240ml of tea with added milk and water than from your 220ml of tea without milk.
Figure 2: Relative changes in FRAP values of Tea 1 due to milk addition compared to the addition of the same amount of water (data calculated based on Ryan. 2010)
Again, we use our spreadsheet skills and create a graph that represents the relative changes in FRAP values that occur due to the addition of whole, skimmed and semi-skimmed milk to the tea (figure 2) and have to realize that our calculation underestimated the reduction by >2.6%. Consequently, there must be more to the effect of milk on the ability of tea to modulate ferric iron reduction than just a dilutive effect. And what's more, it must in one way or the other be related to the fatty acid content of the milk, with skimmed milk producing an effect that is 'only' 3x more pronounced than that of its full fat counterpart, although the individual antioxidant capacity of the latter is only about 8% greater.

Understanding the results of the study

If we think about the composition of whole, skimmed and semi-skimmed milk two things which are closely related to the fat content come to mind: First, low fat milk contains more carbohydrates than full fat milk. And, secondly, the low fat variety also has more protein on a liter per liter base than its full fat precursor. On the other hand, previous studies Ryan & Petit mention in their discussion found a profound interaction of tea polyphenols and protein.
Polyphenols can not only bind to proteins, but that the "interaction between flavonoids and proteins affects their antioxidant capacity in vitro".
If you are interested in optics you will also know that skimmed milk derives its bluish tint from the absence of fat globules, so that only the rayleigh-scattered high frequency blue light from the casein proteins hits the retina of your eye. If you combine that knowledge with the findings of Luck et al. (Luck 1994) who found that proline-rich proteins such as casein have a very high binding affinity for polyphenols, the answer to the influence of the macronutrient composition of the different types of milk is apparent: The casein fraction which is particularly high in skimmed milk binds to the beneficial tea polyphenols and thus decreases its antioxidant capacity. Well, I guess this would be our answer, then: Adding milk to your tea is not advisable, because its protein content will bind the beneficial polyphenols. And yes, it would be, if there were not the two other studies our initial PubMed search had brought up, which report no effect of milk on the total antioxidant capacity of black tea?

Is the newer study always right? Not one study is like another.

The easiest way to tackle the conflicting data would be to assume that the 2010 study is likely to be more accurate than the 5 and 10 years older studies by Reddy and Leenen, but would that be scientifically valid? I don't think so. So what do we do? We take a closer look at the methodology of the Reddy and Leenen studies... it won't take us long to find that in contrast to the Ryan & Petit, both Reddy and Leenen analyzed serum samples of subjects after ingestion of the respective tea+water / tea+milk mixtures. This major, yet easily overlooked difference is of great importance, because it does not take a rocket scientist to know that one of the fundamental functions of our digestive tract is to disassemble the food we consume so that the cells in the endothelial lining of our intestines can absorb the nutrients and deliver them to our bloodstream. Analyzing the ferric reducing ability of human plasma after the subjects consumed a tea + water / tea + milk mixture is thus completely different from putting the mixtures themselves to test.

With the influence of digestion, it is quite obvious that both the ingestion time, or rather the status of the digestive tract at that moment the subjects consume the samples, as well as the time at which the blood for the analysis is drawn post ingestion of the teas is of paramount importance. In both the Reddy and the Leenen study, the subjects reported to the laboratory fasted, and the studies also share some problems in regard of the tea preparation.
  • Reddy, for example used only 280ml of water for the preparation of the tea to which then 70ml milk would be added. Since there is however a saturation level for the maximal amount of antioxidants a unit volume of water is able to hold, the 'no milk reference sample', which had been boiled in 350ml of water, probably had an (unfortunately unquantifiable) 'antioxidant advantage' over the 'milk sample'. 
  • In the Leenen study, on the other hand, the milk was just added to an accordingly reduced amount of tea (60ml milk to 240ml tea vs. 300ml tea), which does also reduce the overall amount of tea polyphenols, the subjects in the tea + milk groups were consuming. 
Both of these minor flaws could explain - to a certain degree - why the subjects exhibited slightly lower increases in serum FRAP (-17% Reddy; -23% Leenen smaller area under the FRAP curve sampled in four and five 30 minute intervals after ingestion of the sample, in Reddy and Leenen, respectively) when they consumed their tea with milk.

So what? Does milk destroy the antioxidant value of tea?

Unfortunately, we cannot be sure that the aforementioned methodological crudities in the studies by Reddy and Leenen can adequately explain the milk-induced reductions in total antioxidant uptake. The -23% reduction in total ferric to ferric ion reduction capacity Leenen et al. measured in their study does yet match the reduced intake of tea polyphenols in the 240ml tea + 60ml milk vs. the 300ml tea group (-20% less polyphenols) pretty well. In view of the fact that Leenen et al. also used 2.5 times more whole milk (20% milk in tea vs. 8% milk in tea) than Ryan & Petit in their in-vitro study, one could do another ignorant calculation in order to estimate how effective our digestive system cleaves the proteins from the polyphenols:
5.73% of the total polyphenol content of 220ml tea are bound by the addition of 20ml whole milk; thus 20ml whole milk can bind the polyphenols from 12.606 ml of tea and 60ml of whole milk should be able to bind the polyphenols from 37.818ml of tea, so that the subjects  in the Leenen study who consumed their tea with milk should be missing an additional 15.7575% of the antioxidants, not just meager 3%, which would ultimately mean that their digestive tract recovered >80% of the protein bound antioxidants from the milky brew. [note - this calculation ignores that the milk would have an antioxidant value by itself, as well]
No matter how "scientific" these funky figures with 4 decimal places may appear - in essence the whole calculation did not only oversimplify the matter to a degree bordering bloggerish pseudoscience. It assumes, for example, a linear binding affinity, i.e. more milk = more binding, which obviously goes against what Ryan and Petit have found (cf. fig. 2). More importantly, though, it was also completely unnecessary in view of the fact that the 'missing' 3% we tried to explain are statistically non-significant, because standard error of the mean AUC (area under the FRAP curve) we based our calculations on is 19.64% and thus more than 6x above the loss we were going to lose our sleep over.

Before we go into even more speculative, or should I say outragous (?) calculations on the influence of the ratio of tea to water on the total amount of antioxidants present in tea after 3 minutes of infusion, in order to do similarly meaningless calculations for the Reddy study, we better bring this highly educative issue of our (almost) weekly Ask Dr. Andro column to a close and summarize our results as follows:
  • the protein fraction in milk can bind antioxidant molecules in tea
  • the antioxidant value of the tea + milk mix is reduced by up to -18% depending on the type and amount of milk you are using
    • skimmed, i.e. low fat, 'high' protein milk reduces binds more antioxidants than whole milk
    • the effect of milk on polyphenol binding in tea is non-linear or, in other words, if you double the amount of milk you won't lose twice as much of the antioxidants
  • in in-vivo studies, i.e. studies that analyze the sera of living human beings after consumption of tea and tea + milk samples, the increase in serum FRAP (Ferric reducing ability of plasma) has been found slightly reduced by the addition of relatively high amounts (20%) of milk, but...
    • this did not compromise the desired positive downstream effects on health markers measured in the Reddy study and
    • the lower FRAP values after ingestion of the tea + milk mixtures could be reducible to the individual study design
And last but not least, there are the results of the Reddy study, which suggest that the effect is similar in both green and black tea. The effects discussed in this article are thus very likely occuring for the all forms of "tea" (a brew created from camellia sinensis leavey), regardless of how the leaves were treated before you put them into hot water.
Bottom line: No matter which "color" your tea has, be it green, black or white, if you enjoy drinking your tea with milk, continue doing so, but do not use a tea bag! The magic of drinking tea goes way beyond the mere physiological effects of its ingredients, anyway (eg. Keenan. 1996); and having to force your tea down without milk, because you want to "waste" those additional 3% or whatever percent of antioxidants, would certainly do more harm than good. Well... when, I am thinking about it, it would go well with the fashionable dietary self-chastisement that is so popular among the followers of certain self-proclaimed Internet gurus (suggested read Sean Casey's "The Guru I am Not"), these days... whatever, I guess I better shut up and get some tea (lprepared from loose laves, with whole milk!), before anybody feels offended ;-)

Ask Dr. Andro: What Are Human Equivalent Doses (HED) and How Do I Calculate Them?

Image 1: Rat & guinea pig. Both very
popular animal models. Both about the
same size and weight, but with very
different reactions to identical treatments.
I won't waste too many words on this being a new series on the SuppVersity, I suppose the name "Ask Dr. Andro" is self-explanatory. It is based on questions posted in the comment section that are relevant for the majority of the visitors and require and deserve a more sophisticated response. So, if you want your question answered, learn a lesson from "Learner" who posted the following question in the comment section of "Spicing Up Fat Loss: Structural Similarity to Melanocortin-4 Agonists Powers Piperine's (Black Pepper Extract) Fat Loss and Lipid Lowering Effects".

Question from "Learner": Why is the mg/kg dosing ratio different for humans than rats, and does that vary by the agent?

Answer from Dr. Andro: Most of what we know about the effects of (new) drugs, supplements, vitamins, minerals, diets, macronutrient ratios and all the other stuff you read about here at the SuppVersity are derived from animal studies. The reasons thereof are manifold:
  1. Animal models are "save" - you do not risk a human life, if you test your new drug on a rat, so this is "safe" for humans
  2. Animal models are cheap and readily available - just order a bunch of lab mice, a few cages and the respective chow and get going; even in the days of slavery that would have been way more difficult with human beings
  3. Animal models (at least some) are easily genetically modifiable - turn off a gene and see what it does
  4. Animal models are time-efficient - if you want to know how life-long supplementation with substance A affects a critter, you better not use a tortoise or your experiment will literally "survive" you
  5. Animal models have an endless list of other advantages, I do not want to list here, because they are not really relevant for the question at hand...
Notwithstanding all these benefits, as a faithful visitor of the SuppVersity you will be familiar with the problems that arise in interpreting data from studies conducted on one species in view of expected results of similar experiments conducted with another species. Even rats and mice can react very differently to a given substance and despite their similar weight and seize guinea pigs and rat models can by no means be used interchangeably.

But let's get back to the "human equivalent" - obviously, two of the most apparent differences between human beings and rats, are body size and body weight. As you probably know, most studies provide information about dosages relative to body weight, so that, for the reader, the difference in body weight would not matter, anyways. Unfortunately a direct translation of the effects observed in a rodent model to a human scenario, based solely on body weight turns out to be very misleading.

Example 1 (this is how it is not done): A very prominent example, where the futile effort of calculating human equivalent doses simply by multiplying the given dosages with the weight of an average human being, lead to major (public) confusion, were the studies on the beneficial effects of the red wine polyphenol resveratrol by Joseph A. Baur et al. (Baur. 2006) and Marie Lagouge et al. (Lagouge. 2006) that were interpreted by the "laypress" as meaningless, because the purported "equivalent" dosages (as mentioned before, calculated solely by multiplying the dose used in the study by the weight of an average human being, cf. figure 1) would amount to hundreds, if not thousands of liters of red wine per day.
Figure 1: Example of a simplistic (and inappropriate) calculation of the human dose equivalent.
This procedure, apparently fails to take into account that oxygen utilization and caloric expenditure are much greater in rodents than in human beings, or in other words: rodents burn through food and metabolize drugs, supplements and whatever you feed them much faster than humans. In the very extreme this may mean that what is a very small dose kilogram per kilogram for a mouse, may well kill an adult human being within minutes.

Image 2: Max Rubner was
probably the first to collect
reliable data on the correlation
of surface area, caloric expen-
diture and oxygen consumption
in mammals (image from The
Eskind Biomedical Library

at the Vanderbilt University)
Thanks to the meticulous research of the German scientist Max Rubner (Rubner. 1883), we do yet know that, in most mammals, both oxygen utilization and caloric expenditure correlate quite well with the ratio of the surface area of the critter to its body weight. An average laboratory mouse, for example, has a very small body weight of ~20g and a comparably large surface area of roughly ~0.006m². An average, normal weight male human being (height 1.73m), on the other hand, weighs roughly ~70kg and has a relatively small surface are of ~1.9m². This means that a man weighs about 3500x as much as a mouse, yet his surface area is only 316x larger than that of the small rodent.

You may now ask yourselves how all that relates back to energy expenditure and metabolic rate - well, no matter how thick the fur of the mouse may be, there is no way for the little critter to escape the basic laws of thermodynamics, which state that the heat flow (for the mouse heat loss) across the surface of an object is proportional to its surface area. On a pound per pound base, the mouse will thus expend way more energy than the man just to keep its body from cooling down.

With that being said, it should be quite obvious that the ratio of body weight [in kg] to surface area [in m²], the so called Km factor, can be used as a relative measure of the metabolic rate of an animal. Using the previously given data, we can now calculate Km factors of Km =3 and Km=37 for mouse and man, respectively. Then, the ratio of the two, Km(mouse)/Km(man) = 0.081 = 8.1%, indicates that the human metabolism runs at 8% of the metabolic rate of a mouse, or in other words, mice metabolise whatever supplement or medication you feed or inject them at a 12 times higher rate than human beings. If you compare that to the respective respiratory ratios of 165 breaths per minute for mice and 12-20 breaths per minute for healthy adults, the aforementioned correlation between body weight and surface area on the one hand and metabolic rate and oxygen consumption on the other becomes quite obvious.
Now, we can save ourselves future troubles associated with the experimental determination of the aforementioned metabolic parameters for each and every species (and animals of the same species, yet with different body sizes / form, e.g. children vs. adults) if we just collect the respective data on body weights and surface areas, and tabulate the respective Km values. Using these values we can easily calculate the equivalent doses for a given species by using the following equation (cf. Reagan-Shaw. 2008):

HED (mg/kg) = Animal dose (mg/kg) * (Animal Km : Human Km)

Where the term in (mathematically unnecessary brackets) would be a conversion factor given by the ratio of the Km value of the species that was used in the respective study to the Km value of the target species. For the majority of the studies you will find on the SuppVersity, the original study was done on mice (Km = 3) or rats (Km = 6) and the conversion factors which are probably of greatest interest for you, i.e. the ones for humans would be 3/37=0.081 for mice (cf. discussion above) and 6/37=0.162 for rats, respectively.
The people from the FDA, who always tend to think nobody could be half as smart as they are, obviously wanted to play safe and included these "conversion factors" along with the Km values in their Guidance for Industry on "Estimating the Maximum Safe Starting Dose in Initial Clinical Trials for Therapeutics in Adult Healthy Volunteers" (FDA. 2005):
Table 1: Km values for various species according to FDA Guidance for Industry (FDA. 2005)
Example 2 (this is how it is done): With this new knowledge you can also calculate how much black pepper you would have to consume to achieve the effective dosage of piperine that was used in the study mentioned in the SuppVersity news last Thursday. With an average piperine content of 3 to 8 g/100g and about 0.2-0.3g/100g of the minor alkaloids piperyline and piperettine in black pepper (Schulz. 2004), a rat would have to consume somewhere between 500-1300mg of black pepper corns per day to achieve the 40mg/kg dose that effectively accelerated the metabolism of the rats in the study by Shat et al. (Shah. 2011). All you have to do now, is look up the Km values of rats (Km=6) and humans (Km=37) and insert the respective values in the given equation, so that

HED(40mg/kg in rats) = 40mg/kg * (6 kg/m² : 37kg/m²) = 6.5mg

would yield the amount of piperine and

HED(1000mg/kg in rats) = 1000mg/kg * (6 kg/m² : 37kg/m²) = 162mg

the amount of pepper corns you would have to use to achieve the "same effect" in human beings.

A final word on the italicized "same" in what would otherwise be the last sentence of this article: You will probably never see identical effects across different species, regardless of how exact you try to calculate the equivalent doses. There are simply too many differences between mice and men and the way they metabolize different substances to be able to translate results from experiments with oftentimes fundamentally different agents from mice to men and vice versa using nothing but the ratio of body weight to surface area as your guide. Consequently, you should consider human equivalent doses as a means to interpreted whether or not animal data is practically relevant and what amounts of a given substance would roughly have to be used in follow up studies to evaluate whether or not the results can be reproduced in human beings.