Consumer’s Reports published a report on health risks associated with protein powders, including a discussion of the risks associated with heavy metal contaminants found in some brands of powders. I’ve commented previously on the shortcomings in their reporting of the risks from the heavy metal contaminants, which I predict will do more to alarm and confuse people than inform them (Note that a condensed version of this post without all of the geeky risk assessment talk can be found here).
However, far be it for me to simply criticize CR’s work without making the attempt to try and communicate health risk issues with heavy metals in protein powders more clearly. So, I’ll take a run at talking about cadmium, because I kind of ran arsenic into the ground with the last post.
So, what’s the nature of the problem we are trying to address? According to CR’s testing, a few protein powder products contain cadmium concentrations that are higher than the U.S. Pharmacopeia’s permitted daily exposure (PDE) limits. We’ll defer for a moment the question of how much information CR’s testing actually provides about potential cadmium exposure from consuming protein powders – simply publicizing that any cadmium has been detected has been sufficient cause to elevate concerns about adverse health effects in the minds of consumers.
The toxic effects of cadmium on humans have been extensively studied.* Humans consuming cadmium-contaminated rice in Japan have experienced adverse effects in the kidney and bones. Inhalation of cadmium by workers in certain industries has also been associated with kidney toxicity (inhalation by workers is associated with other effects such as lung diseases including lung cancer, but we’re interested in the risks from ingesting cadmium). There is conflicting evidence as to whether or not cadmium exposure produces high blood pressure in humans; cigarette smoking is an important source of cadmium exposure, but by itself may be a confounding factor. Excessive cadmium ingestion exposure in combination with low dietary intake of iron may be associated with anemia.
These pieces of information are useful in understanding the kinds of toxic effects that could be associated with cadmium exposure, based on what human populations have experienced in the past – typically from elevated levels of exposure. However, these aren’t enough by themselves; there is additional information that needs to be considered to better understand how exposure under a specific circumstance (using protein powders, for example) could pose a health risk.
For example, elevated levels of exposure to cadmium are associated with an increased risk of kidney disease. Lower levels of exposure do not produce observable kidney disease, but will be associated with an increased prevalence of abnormal biomarkers. In this case, the abnormal biomarkers would be increased levels of certain low molecular-weight proteins in the urine. These biomarkers are the earliest and most sensitive indications of changes in kidney functioning. Some accumulation of cadmium in the kidney without apparent toxic effect is thought to be possible because cadmium in the kidney becomes bound to a protein called metallothionein. However, when cadmium levels in kidney tissue become high enough, the amount of cadmium not bound to metallothionein becomes high enough to cause kidney toxicity.
Effects to the bone (osteoporosis, increase in bone fractures) were first observed in Japanese women living in areas with high cadmium contamination. This was a disorder referred to as “itai-itai” (ouch-ouch) disease. Other factors that may have been important in itai-itai disease included multiple pregnancies, poor nutrition (low calories, reduced calcium, protein, vitamin D, iron and zinc intakes). The adverse effects in bones occur in the presence of kidney disease from cadmium exposure, and the kidney is thought by some to be a more sensitive target organ for cadmium toxicity. Other researchers argue that effects to the bones, such as osteoporosis, occur at the same levels that produce kidney toxicity. However, currently, the limits on cadmium exposure used to assess the risks of dietary intake consider the kidney to be the most sensitive target organ.
The excretion in the urine of biomarkers (low molecular-weight proteins) has been shown to increase due to cadmium-related alteration in kidney function; alteration in these biomarker levels is considered the most sensitive toxic effect from cadmium exposure.
This information has been used to identify a cadmium exposure level in humans associated with minimal health risks.
The Agency for Toxic Substances and Disease Registry (ATSDR) used a 10% increased risk of low molecular-weight proteinuria (proteinuria – excretion of excessive levels of protein in the urine) as an indication of cadmium-associated kidney toxicity. Selection of the 10% value is based on a typical limit of detection for adverse effects in health effects studies. ATSDR reviewed numerous scientific studies and estimated the cadmium dose in the body corresponding to the 10 percent increased risk of low molecular-weight proteinuria; that internal dose was estimated in those studies from the levels of cadmium measured in the urine of exposed persons (the researcher’s short-hand for describing this internal dose is the “urinary cadmium dose, 10%” or UCD10).
The next step is to estimate the daily intake rate of cadmium into the body that corresponds to the UCD10. This uses the results from a “physiologically-based pharmacokinetic model” (the short-hand is “PBPK model”). The PBPK model provides a mathematical description of the absorption, distribution throughout the body, accumulation in target organs and excretion of ingested cadmium. The results from the PBPK model can then be used to relate the UCD10 to a daily intake rate over a lifetime. That daily intake rate is known as the Minimal Risk Level (MRL). The MRL is defined by ATSDR as: “an estimate of daily human exposure to a substance that is likely to be without an appreciable risk of adverse effects (noncarcinogenic) over a specified duration of exposure.”
This is the approach that U.S. Pharmacopeia (USP) used to develop its Permitted Daily Exposure (PDE) value for cadmium. As USP described it:
Using data from select environmental studies examining the relationship of urinary cadmium and the prevalence of elevated levels of biomarkers of renal function ATSDR issued the provisional Minimal Risk Level (MRL) for chronic cadmium exposure. The 95% lower confidence limit of urinary cadmium dose corresponding to the probability to exceed in 10% the risk of low molecular weight proteinuria has been estimated as 0.5 ug/g creatinine, assuming accumulation over a 55-year period. This value corresponds to an intake of 0.33 ug/kg/day in females, for which, applying a safety factor of 3 for human variability. ATSDR has set the MRL to 0.1 ug/kg/day.
The factor of 3 for human variability takes into consideration sensitive individuals (I talk more about sensitive individuals in a moment). There are also a couple of critical assumptions to be aware of here. First, the 95% lower confidence limit of the UCD10 is used to calculate the corresponding daily intake rate (i.e. the MRL). The lower confidence limit provides for a more protective daily intake rate. Second, the UCD10 is based on constant exposure to cadmium over a 55 year lifetime. I come back to this latter point when discussing scenarios that may be associated with increased risks from cadmium exposure.
USP assumes that an individual with a 50 kg body weight (about 110 lbs) is exposed to the MRL of 0.1 ug/kg-day to calculate the PDE of 5 ug/day (0.1 x 50 = 5).
So far, we’ve identified the key adverse effects associated with cadmium ingestion, and we’ve quantitatively evaluated the levels that produce adverse health effects. Recall from the previous post these were two of the three critical pieces of information needed to properly assess the health risks from heavy metals exposure. The third piece of information is to explore the patterns and magnitude of human exposure to cadmium.
For nonsmokers, dietary exposure to cadmium is the most likely route of exposure. Cadmium is naturally occurring in soil and water, and can accumulate into the food chain. Cadmium levels in food can vary depending on the type of food, agricultural practices, the amount of atmospheric deposition (particles in air that deposit onto the ground) and industrial contamination in soil. In general, leafy vegetables, grains, root vegetables and seeds (nuts and sunflower seeds) have higher levels of cadmium than other foods. Organ meats such as liver and kidneys, and seafood, concentrate cadmium and therefore have relatively higher levels. Dairy products, beef and poultry, and fruits have relatively lower levels of cadmium.
The Food and Drug Administration (FDA) performs laboratory analyses of metals in food as part of its Total Diet Study (TDS). The TDS data might be a good way of comparing with other foods the cadmium concentrations reported in protein powders by CR; that is, if CR had actually reported concentration data (the problems with CR’s analytical results are a topic for another post). CR’s lack of transparency in reporting metals data for protein powders makes it difficult to compare the risks relative to other foods.
Maybe there’s another way to get at this. Based on food intake rates and concentrations in foods, a typical daily intake of cadmium for the U.S. population is estimated to be 18.9 micrograms per day or ug/day (note for the more scientific types: that statistic is the geometric mean). According to CR’s data, cadmium exposures from protein powders and drinks range from 1.6 to 5.6 ug/day (based on the assumption that someone consumes three servings per day). It could be difficult to argue that the cadmium intake is in addition to the daily intake from other foods; part of the criticism of protein powders is that they are consumed to the exclusion of other foods. Without answering this question about how cadmium exposure from consumption of protein powders relates to cadmium exposure from all dietary sources, it is difficult to argue either that protein powders significantly increase one’s risk of adverse effects from cadmium OR do not increase one’s risk.
How about some examples? I created some hypothetical healthy meals that people trying to get lean or stay lean might eat. Using the TDS cadmium data (note for the nitpicking types, I just used the first quarter 2005 data – FDA samples foods quarterly as part of the TDS – I’m just trying to quickly get a rough indication of exposure here), I estimated the cadmium intake with these meals. I’ll have to share the calculations in another post, because this is getting pretty long now by blog standards, and there are still a number of points that need to be made. I present a range of estimated cadmium intakes, because of how the TDS reports non-detected analytical results.** These examples are as follows:
- Breakfast consisting of two scrambled eggs, 1 cup of oatmeal and 6 oz of grapefruit: 1.07 to 1.21 ug cadmium.
- Snack consisting of 2 oz of peanut butter, two slices of whole-wheat bread and a banana: 2.05 to 2.4 ug cadmium.
- Dinner consisting of an 8 oz chicken breast, one cup of steamed broccoli and a cup of rice: 4.1 to 4.6 ug (the grains and veggies contained the higher concentrations of cadmium).
- A spinach salad with mushrooms, an ounce of shredded cheese, whole wheat croutons and Italian dressing weighs in at 4.8 to 4.9 ug – with most of the exposure coming from the vegetables.
As CR tells us, consuming three servings of protein drinks or protein powders corresponds to 1.6 to 5.6 ug of cadmium. Eyeballing all of these numbers indicates they all (from the protein powders and example meals) fall within a narrow range – between 1 and 6 micrograms, and the exposures from the protein powders don’t look terribly distinguishable from the meals. The point here is to not scare you about eating real food. In a narrow sense, it’s probably correct that other sources of protein such as meat, milk and eggs provide lower exposures to cadmium. However, if protein powders or drinks are being used as meal replacements, particularly if they are replacing consumption of grains, nuts and vegetables, then the difference in cadmium exposure with or without protein powders in the diet is probably insubstantial.
There are factors that could make an individual more susceptible to cadmium exposure than most, including age, general health and nutritional status, other sources of exposure to cadmium (for example, cigarette smoke), and exposure to other toxic substances – say mercury, for example. These factors could affect how well cadmium is absorbed in the body, or could reduce the capacity to detoxify or excrete cadmium. In addition, organ damage from preexisting diseases could affect cadmium toxicity. Smoking substantially increases cadmium exposure. Nutritional deficiencies, such as calcium or iron deficiencies, could increase cadmium absorption from the gastrointestinal tract – though this has not been demonstrated consistently in all of the pertinent studies. Protein deficiencies could affect a person’s ability to detoxify cadmium. Individuals with decreasing kidney function from unrelated causes – such as diabetes or aging – could be more sensitive to adverse effects from cadmium.
So, what kind of a scenario could we envision for an individual who could be at risk from ingesting cadmium in protein powders, if we overlay CR’s paradigm with some of the known risk factors. What comes to mind for me is this: a skinny hard-gainer teen-aged kid who, in addition to consuming a lot of protein powder also eats a lot of spinach, sunflower seeds, whole-wheat bread and oatmeal. He or she would either be employed or have well-off parents in order to afford all of the protein powder being consumed. He or she also would have kidney problems related to diabetes or some other preexisting condition. Bonus points for being a smoker. Keep all of this up through middle-age, and this individual might be at an appreciable risk of kidney toxicity or osteoporosis from cadmium exposure.
This in no way is being dismissive of the health risks from cadmium, though I hope it’s been a useful counterpoint to the faulty messages in CR’s article. There are recent scientific papers (here, here and here) highlighting cadmium as a public health concern, noting that the most recent evidence suggests the margins of safety are very small or inadequate between levels that could begin to produce adverse effects and normal intakes from diet and smoking (so don’t smoke, already). However, it’s important to keep in mind that the MRL (which again is the threshold for the most sensitive effects from a lifetime of cadmium exposure, reduced by an additional factor of three, and is also the number used by USP for assessing cadmium levels in diet supplements) is as protective as feasible, based on the available scientific information. Would occasional fluctuations in exposure above that level cause harm? That would depend – how large were the fluctuations, how often did they occur and did they occur to someone who is a sensitive individual, like a diabetic, a smoker or someone already experiencing kidney disease. The take-away point from this analysis, for me at least, is that in normally healthy people including protein powders and drinks in conjunction with a healthy diet (and not smoking. . .) shouldn’t appreciably be increasing exposure or risk from cadmium.
Ultimately, it’s up to you what you do to maintain and enhance your health. Some of the experts that CR interviewed did folks a disservice by saying in effect you shouldn’t consume protein powders because the heavy metals in them might increase the risk of adverse health effects; instead, they should have taken the time to explain to people as clearly as possible what those risks might be, and provide the information balancing benefits versus risks of protein powders – information that might be more useful in helping users make their own decisions about using these products. But that’s a harder thing to do – the topic just doesn’t fit into a sound-bite, which is all that the authors allowed from these experts (I’ve expended about 2,800 words on it so far, and still have only scratched the surface). The writers of the article in CR just didn’t try very hard, and the sound-bites they provided generally were pretty un-informative for users of protein powders about the relative benefits and risks.
Stay tuned. I’ve got three more contaminants to go through. The shorter version of this post minus the extended analysis can be found here.
Notes:
*Much of the discussion of cadmium-related adverse health effects in humans has been drawn from the ATSDR’s toxicological profile for cadmium.
**The TDS will report foods in which no cadmium was detected as zero mg/kg (milligrams of cadmium per kilogram of food). However, the TDS also will report the “limit of detection” or LOD, which is the lowest concentration that the analytical method used on the food could detect. So, if the TDS reports for whole milk a cadmium LOD of 0.002 mg/kg (or ug/g, microgram cadmium per gram of food), that means that cadmium intake associated with consuming an 8 oz cup of milk (226 grams) is probably less than 0.45 ug, though how much less might be difficult to say. So, I reported a range of estimates – one without the LOD (foods reported as not detected are treated as zero) and one with the LOD (foods reported as not detected are assumed to have contamination at the LOD). Again, this is a topic for a separate post.