All ten foods were found to contain levels of lithium above the limit of detection, but some foods contained a lot more than others — ground beef contained up to 5.8 mg/kg lithium, corn syrup up to 8.1 mg/kg lithium, and goji berries up to 14.8 mg/kg lithium.
But of the ten foods we looked at, eggs appeared to contain the most, up to 15.8 mg/kg lithium when analyzed with ICP-OES:
The Results of the Previous Study
So for our next study, we decided to look at more eggs.
The first reason to look at more eggs was to confirm the results of our first study, and confirm that these numbers could be replicated.
The second reason to look at more eggs was to start getting a better sense of the diversity of results. Where the first study gave us a small amount of breadth by comparing several foods, the second study would give us a small amount of depth by comparing several eggs.
The third reason to look at more eggs was that we might be able to find an outlier, a sample of food that contains far more than 15 mg/kg lithium. Eggs containing 15 mg/kg lithium are somewhat of a public health concern; how much more concerning would it be to find eggs that contain 50 mg/kg, or 100 mg/kg.
(There are reports of such outliers in other foods, in particular from work by Sievers & Cannon in the early 1970s, who reported an “extraordinary” lithium content of 1,120 mg/kg in wolfberries from the Gila River Valley.)
Special thanks to all the funders, Sarah C. Jantzi at the Plasma Chemistry Laboratory at the Center for Applied Isotope Studies UGA for analytical support, and to Whylome for providing general support.
The technical report is here, the raw data are here, and the analysis script is here. Those documents give all the technical details. For a more narrative look, read on.
2. General Methods
2.1 Eggs
First, we collected a sample of eggs from grocery stores around America.
We started by purchasing several cartons of eggs from grocery stores near Boulder, Colorado. We bought several different brands, and tried to get a fair mix of eggs, both white and brown, conventional and organic.
However, this was still not enough diversity for our purposes. So in the meantime, we asked friends from around the country to mail us cartons of eggs.
Fun fact: Eggs don’t actually require refrigeration, Americans are basically the only weirdos who even keep them in the fridge. Especially when it’s mild outside, they keep for many weeks at room temperature. So shipping these eggs was relatively easy — really it’s just about packaging them with lots of padding so they don’t break. Most of the eggs arrived intact and we’re very grateful for the great care in packaging and shipping taken by our egg donors (ha).
The list of eggs is summarized in greater detail in the technical report.
From most cartons, we took two samples of 4 eggs. This gave us two measurements per carton, which should give us some sense of how much variation there is within an individual carton.
Each sample was homogenized/blended with a stick blender for 1 minute to obtain a smooth, merengue-like texture. The blended mixture was then transferred to drying dishes and dried in a consumer-grade food dehydrating oven.
We also pulled out one brand for more testing, to assess individual egg-to-egg variability. From the carton of Kroger Grade AA, we took two samples of 4 eggs as normal. Then we took three more samples of individual eggs. The single eggs were blended and dried just as the larger 4-egg samples were.
When all samples were dried, they were crumbled into a powder, weighed, put into polypropylene tubes, and shipped off to the lab for further processing.
2.2 Digestion
Food samples need to be digested before they can be analyzed by ICP-OES. Based on our results from the previous study, we used a “dry ashing” digestion approach, where samples are burned at high temperatures, and the ash is dissolved in nitric acid.
Incineration causes organic compounds to exit the sample as CO2 gas, but elements like sodium, potassium, magnesium, and lithium are non-volatile and remain behind in the ash.
2.3 Analysis
ICP-OES generates a tiny cloud of high-energy plasma, the “inductively-coupled plasma” of the acronym, and injects a cloud of liquid droplets into that plasma (hence the need for digestion). ICP-OES then examines the light that is emitted by the plasma as the liquid sample hits it.
In addition to lithium, we also analyzed all samples for sodium. Sodium is chemically similar to lithium, and most foods contain quite a lot, which nearly guarantees a good signal in every sample.
This makes sodium a useful point of comparison. At every step, we can compare the lithium results to the sodium results, to see if general patterns of findings match between the two elements.
3. Results
All samples were analyzed as one project, but for clarity of understanding, we’re going to report this project in two parts, as two studies.
In Study One, we look at the main body of results — eggs analyzed as four-egg batches from a single carton.
In Study Two, we look only at the Kroger Grade AA eggs — analyzed as two four-egg batches and three one-egg batches, to assess individual egg-to-egg variability.
3.1 Study One
For starters, here is a histogram of the distribution of lithium measurements in our egg samples:
We’ve previously speculated that the distribution of lithium in food would be lognormal, as it is in drinking water, and indeed this looks very lognormal.
For comparison, here’s the distribution of sodium:
Note that the x-axis is extremely different between the two plots! This is not surprising; eggs contain a lot more sodium than lithium.
For a sanity check, the USDA says that “Egg, whole, raw, fresh” contains 142 mg sodium per 100 g egg. Converted, that’s 1,420 mg/kg, which approximately matches these results, though the mean in this sample is much lower at only 987.3 mg/kg. The median is 963.0 mg/kg, and the standard deviation is 288.8 all told.
Slightly surprising are those three samples that (according to the analysis) contain almost no sodium — their values in the data are 7.6 mg/kg, 1.5 mg/kg, and one measurement below the limit of quantification.
3.1.1 By Batch
More interesting is the breakdown by batch.
As a reminder: each carton of eggs (aside from the Trader Joe’s eggs, due to an oversight) was used to create two batches of four eggs each. Then, each batch was tested in triplicate, so each carton was tested six times. Here, each bar indicates a batch. Each batch has three dots, representing each of the three results from the tests done in triplicate:
The main finding is that lithium was detectable in nearly all eggs. This suggests that ICP-OES is more than sensitive enough for this type of work, and that in general, eggs contain appreciable levels of lithium.
Most egg samples contained between 0.5 and 5 mg/kg. The few readings of “zero” in the plot actually mean “less than about 0.04 mg/kg moist weight”.
Hypothetically speaking, the batches were all well-mixed. Eggs were blended with a stick blender for a full minute (to a very creamy consistency, think meringue), then dried and crumbled, and the dried bits mixed up. So it’s quite surprising that after all that, there’s so much variance within the batches.
Some of the batches show close agreement between different samples from the same batch. Both Simple Truth AA batches have only a very small amount of variation. Whole Foods Batch 2 is bang on every time.
But other batches show a lot of variation. Batch 1 of Organic Valley and Batch 1 of Eggland’s best both contain one sample that is a huge outlier. You might dismiss these as some kind of one-off analysis error. But some of these cases, like both CostCo batches or the first Land-O-Lakes batch, show disagreement between all three samples.
We wondered if this might mean that these batches were imperfectly blended. This would be quite surprising, given the lengths we went to to ensure that the batches were well-mixed.
If the batches were perfectly blended, then all three samples should contain identical levels of lithium. The only differences between the results would then be errors in the analysis, not real differences in the samples. But if errors were the only source of noise, you would expect to see similar levels of variation in every batch.
Two explanations seem likely.
First, lithium is very strange. In our last study, we saw that sometimes you get very different numbers for the exact same piece of food. Maybe the differences between different samples from the same batch comes from the fact that it’s hard to get accurate measurements for lithium levels in food.
Second, perhaps eggs are just goopy. It’s possible that despite our best efforts to completely blend the samples, they are still less than perfectly mixed, so some samples from the same batch contain more or less lithium than others.
We can test these explanations by comparing the lithium results to the sodium results for the same set of batches and samples. If the variance is the result of a problem with lithium detection, then the sodium results should be much more consistent within batches. But if the variation comes from the eggs being imperfectly blended, then we should see similar variation in the sodium results as in the lithium results.
3.1.2 Sodium
Here are the sodium results:
Sure enough, there is a lot of variation between sodium levels, even within single batches. This suggests that the variation we saw in the lithium results is not the result of something weird about lithium. It’s probably something general about the samples or the analysis.
Some of the variation in sodium lines up with the lithium results. The Whole Foods batches show great precision for both lithium and sodium, suggesting that they are especially well-blended or homogenous or something. But there is also some disagreement. For lithium, Organic Valley Batch 2 was much more precise than Organic Valley Batch 1. For sodium, it is the opposite.
Sodium does show something unique — three very clear outliers with readings of almost exactly zero sodium (specifically 7.6 mg/kg, 1.5 mg/kg, and one reading below the limit of quantification).
These look like errors of the analysis rather than real measurements. All three are outliers from the sodium data in general, more than three standard deviations below the mean. All three are from different batches and starkly disagree with the other samples from that batch. And we have strong external reasons to expect that any bit of egg will contain more than zero sodium.
In addition, we notice that these three cases with exceptionally low sodium levels are the exact same three cases that registered as below the limit of quantification for lithium. This suggests that none of these readings are real, that there were three samples where something went wrong, and the analysis for some reason registered hugely low levels of sodium and no lithium. If true, that means that all real measurements detected lithium above the limit of quantification.
The other variables we considered, like location, egg color, and whether or not the eggs were organic, didn’t seem to matter. Maybe differences would become apparent with a larger sample size, but they’re not apparent in these data.
3.2 Study Two
You might expect that hens from the same farm, eating the same feed, would all have roughly similar amounts of lithium in their eggs. For the same reason, it seems likely that any two eggs in the same carton wouldn’t be all that different, and would contain similar amounts of lithium.
All the above seems likely, but we actually have no evidence. It’s an assumption, and exactly the kind of assumption that could really confuse us if we assume wrong. It’s worthwhile to check.
Certainly the results from Study One call the assumption into question. A thoroughly blended mix of four eggs seems like it should have homogenous levels of lithium throughout. But empirically, that isn’t what we saw. We saw a lot of variation. Maybe the variation within those 4-egg batches comes from differences between the four eggs.
To test this, we did another round of analysis, focusing on a single carton of Kroger eggs. As before, of the 12 eggs in the dozen we took two groups of four to create two four-egg batches.
In addition, we took three of the remaining four eggs, and used them to create three one-egg batches, mixing and sampling just that single egg. The one-egg batches each consisted of a single egg from this carton, blended well. The one-egg batches were also tested in triplicate, i.e. three samples from the same egg.
Here are the results:
These four-egg batches look much like the four-egg batches tested in Study One. They show a lot of variation between the samples tested in triplicate.
The single-egg batches, on the other hand, did indeed have lower variance than the 4-egg batches. There was much closer agreement between different samples from the same eggs, than samples from different eggs. Certainly we see a difference between the egg used for Batch 3, which all samples indicate contains about 1 mg/kg lithium, and the egg used for Batch 4, which all samples indicate contains about 5 mg/kg lithium
This suggests that there really may be appreciable egg-to-egg variation. This could be the result of other factors, including simple randomness, but the tightness of the single-egg analyses is suggestive. And the fact that the variance seems much lower in single-egg batches implies that the mixed four-egg batches are imperfectly blended.
The sodium results for these batches seem to confirm this, with greater variation in sodium in the four-egg batches than in the one-egg batches:
Again, this suggests that the patterns we observe in the lithium data are the result of actual results in the world, or the analysis in general, rather than some artifact of the lithium analysis in particular.
4. Discussion
Nearly all egg samples contained detectable levels of lithium, and around 60% of samples contained more than 1 mg/kg lithium (fresh weight). These results appear to confirm that eggs generally contain lithium.
If you accept the argument that the three samples with conspicuously low sodium readings are the result of a failure of analysis, then all egg samples contained detectable levels of lithium.
In terms of diversity of results, samples varied from as much as 15 mg/kg Li+ to as little as less than 1 mg/kg Li+. Variation did not seem to be related to the geographic purchase origin of the eggs. Nor were there any obvious differences between organic and non-organic, or white and brown eggs. This suggests that these are not major sources of variation.
However, we did see evidence of a lot of variation in lithium levels between individual eggs, even between individual eggs from the same carton.
While there was a lot of variation between samples, some samples showed a great deal of consistency, especially samples from single eggs. This suggests that dry ashing followed by ICP-OES has high precision when analyzing food samples for lithium. Though these results do not speak to whether or not this analytical method is accurate for such samples, they do suggest that these are real measurements and not merely the result of noise or analytical errors.
One of our hopes for this study was to find an egg that contained more than 15 mg/kg lithium, that we could subject to other, less sensitive analytical methods. This would let us get a sense of accuracy by triangulation, comparing the results of different methods when analyzing samples of the same egg.
We did in fact find eggs that contain such high concentrations. Above we reported the lithium concentrations in fresh weight, because those are the numbers that are relevant if you are eating eggs. But in terms of analysis thresholds, the numbers that matter are the dry weight. For dry weight, some of these egg samples contain as much as 60 mg/kg lithium. That’s more than enough to be above the sensitivity of a technique like AAS.
As we are quite interested in trying to confirm the accuracy of lithium analyses in food, one next step will be to replicate these analyses using other analytical techniques like AAS.
There are lots of different methods you can use to estimate the lithium in a sample of food. This usually involves some kind of chemical liquefication (“digestion” in the parlance) paired with a tool for elemental analysis. You need digestion to analyze food samples, because some analysis techniques can only be performed on liquids, and as you may know, many foods are solids or gels. Mmmmm, gels. *HOMER SIMPSON NOISES*
Most modern studies use ICP-MS for analysis of metals like lithium, combined with digestion by nitric acid (HNO3). ICP-MS is preferred because it can analyze many elements at once and it is considered to be especially sensitive. HNO3 is preferred because it is fast and cheap compared to alternatives.
Studies that use HNO3 digestion with ICP-MS tend to find no more than trace levels of lithium in their food samples — only about 0.1 mg/kg lithium in most foods, and no foods above 0.5 mg/kg. Examples of these studies include Ysart et al. (1999), which surveyed 30 elements in a wide variety of UK foods and found no more than 0.06 mg/kg lithium in any food; Saribal (2019), which measured the levels of 19 elements in cow’s milk samples from supermarkets in Istanbul, and found less than 0.04 mg/L lithium in all samples; and Noël et al (2006) which surveyed the levels of 9 elements in “1319 samples of foods typically consumed by the French population”, finding 0.154 mg/kg or less lithium in all foods (though they reported slightly higher amounts in water).
But as we’ve reviewed in previous posts, the literature as a whole is split. Studies that use other analysis techniques like ICP-OES or AAS, and/or use different acids like H2SO4 or HCl for their digestion, often find more than 1 mg/kg in various foods, with some foods breaking 10 mg/kg. Examples include studies like Ammari et al. (2011), which found 4.6 mg/kg lithium in spinach grown in the Jordan Valley; Anke, Arnhold, Schäfer, and Müller (1995) which found more than 1 mg/kg lithium in many German foods, including 7.3 mg/kg lithium in eggs; and in particular we want to mention again Sievers & Cannon (1973), which found up to 1,120 mg/kg lithium in wolfberries (a type of goji berry) growing in the Gila River Valley.
1.1 State of the Art Isn’t Great
From the existing literature alone, it’s hard to say what concentrations are present in today’s food. Different papers give very different answers, and often seem to contradict each other. It’s hard to get oriented.
We don’t want to give the impression that there’s a consensus to be boldly defied, or that there are two opposing camps. It’s more like this: hardly anyone has even tried to do a decent job of even looking for lithium in food or taking it seriously, and we are here to smack them and tell them to pay attention to something that has been ignored. This is not a well-studied question. It is a subject that has been the topic of few papers and even fewer authors. It is a small literature and very confused.
Hardly anyone can even be bothered to look for lithium. When it does appear in a study, half the time it feels just tacked on to a list of things that the authors actually care about (like in the France study above). Many of these studies are really looking for toxic metals like lead and cadmium, which are obviously important things to check for in our food. But this makes lithium an afterthought. And when authors don’t care, fundamental issues of analysis can easily be overlooked. The assumption seems to be that you can just throw everything into the same machine and get a good measurement for every element without any extra effort. But as we’ll see in a moment, that may not be the case.
As we hinted at above, the analytical methods may be the root of the problem. Studies that use HNO3 digestion with ICP-MS report minor trace levels of lithium in food. Studies that use other forms of digestion or other analytical techniques report much higher levels, often above 1 mg/kg. This makes us think that the different analyses are the reason why these papers get such different estimates. However, we couldn’t find any head-to-head comparisons in the literature, and it isn’t clear if the problem lies with ICP-MS, HNO3 digestion, or both.
1.2 Effects of Lithium
This is more than a purely academic question: lithium is psychoactive, and exposure through our food could have real health effects.
Clinical doses, which usually range between 56 mg and 336 mg elemental lithium per day, act as a mood stabilizer and sedative. These doses also cause all kinds of nonspecific adverse effects, including confusion, constipation, headache, nausea, weakness, and dry mouth.
Even the trace amounts of lithium in our drinking water (< 1 mg/L) may have some effects. A epidemiological literature with roots dating back to the 1970s (meta-analysis, meta-analysis, meta-analysis) suggests that long-term exposure to trace levels of lithium in drinking water decreases crime, reduces suicide rates, reduces rates of dementia, and decreases mental hospital admissions, and this is supported by at least one RCT. The EPA is even concerned about exposure to levels as low as 0.01 mg/L and 0.06 mg/L, describing them as “concentrations of lithium that could present a potential human-health risk”, though they don’t say why.
1.3 Measurement
Trusting your methods is the basis of all empirical work. The disagreement in the existing literature is important because we don’t have a good sense of how much lithium is in our food. It’s concerning because it suggests we might not know how to measure lithium in our food even when we try! This looks like a crisis of methods either way.
High enough levels of lithium in our foods would be dangerous, so we should know how to take a piece of food and figure out how much lithium is inside it. But there isn’t much research on this topic, and it looks like different methods may give very different answers — if this is true, then we don’t know how to accurately test foods for lithium. And it’s likely that lithium levels in the environment are increasing due to both lithium production and fossil fuel prospecting — see Appendix B for more.
As an analogy, we should know how to measure mercury levels in fish in case it’s ever a problem — our chemists should be able to check fish samples periodically and get a good estimate of the mercury levels, an estimate we feel we can rely on. Because if we can’t measure it, then we don’t know if it’s a problem. High levels could slip by undetected if our methods aren’t right for the job.
1.4 Head-to-Head
Before we can really figure out how much lithium there is in food, we need to find analytical methods that have our full confidence. And the simplest way to test our methods is a head-to-head comparison.
This seemed easy enough, so we set up a project with research nonprofit Whylome to put a set of foods through different digestions and put the resulting slurries in different machines, and see if they give different answers. By comparing different digestions and analytical methods on a standard set of food samples, we should be able to see if different techniques lead to systematically different results.
Based on the patterns we saw in the literature, we decided to compare two analysis techniques (ICP-MS and ICP-OES) and three methods of digestion (nitric acid, hydrochloric acid, and dry ashing). Details about these techniques are in the technical report, and in the methods section below.
We originally wanted to compare more analysis techniques (AAS, flame photometry, and flame emission methods) but weren’t able to find a lab that offered these techniques – they are somewhat oldschool and not in common use today. More on this below.
It turned out that the type of analysis didn’t make much difference, but the way in which samples were digested for analysis was surprisingly impactful. And the technique that’s most commonly used today seems to underestimate lithium, at least compared to alternatives.
This project was funded by a generous donation to Whylome from an individual who has asked to remain anonymous. General support for Whylome in this period was provided by the Centre For Effective Altruism and the Survival and Flourishing Fund.
Special thanks to all the funders, Sarah C. Jantzi at the Plasma Chemistry Laboratory at the Center for Applied Isotope Studies UGA for analytical support, and to Whylome for providing general support.
The technical report is here, the raw data are here, and the analysis script is here. Those documents give all the technical details. For a more narrative look at the project, read on.
2. Methods
The basic idea is to test a couple different analytic approaches on a short list of diverse foods.
Most modern analyses use either ICP-MS or ICP-OES. Some of these papers find low concentrations of lithium in food; some of them find high concentrations. We wanted to compare these two techniques to see if they might be the cause of the differences in measurements.
Based on what we had seen in the literature, we decided to compare two analysis techniques (ICP-MS and ICP-OES) and three methods of digestion (nitric acid, hydrochloric acid, and dry ashing), fully crossed, for a total of six conditions.
2.1 Food
As this is our first round of testing, we wanted a diverse set of foods that could give us some sense of the American food environment in general. Therefore we were looking for a mix of foods that were animal-based and plant-based, highly-processed and unprocessed, a mix of fruits, vegetables, dairy, carbs, and meats. We also made sure to include some foods that previous literature had suggested could be extremely high in lithium (like eggs and goji berries), to see if we could confirm those results. Twinkies made the cut because they’re highly processed and highly funny.
In the end, we settled on the following list:
Milk
Carrots
Eggs
Ketchup
Spinach
Corn syrup
Goji berries
Twinkies
Ground beef
Whey powder
All foods were purchased in August of 2022 at grocery stores around Golden, Colorado. Foods were immediately dried, blended, and divided into tubes for further processing, with weight measurements taken at each step of the process.
For example, this is how we prepared the eggs. A carton of twelve eggs were cracked into a stick blender, and blended until well-mixed. A subset of the resulting egg blend was then dehydrated, enough to produce all of the needed material with some to spare. The dried egg (more like flakes at this point) was crushed and mixed well. All samples were taken from this egg powder. Three samples each were submitted to every method of analysis, so every result is an estimate of the concentration of the target element averaged across the whole carton. Put another way, our sample size was one (1) carton of eggs, not 12 eggs separately. As the egg blend was well-mixed, all samples should in principle have the same concentration of elements, suggesting that any variation between samples is the result of analytic noise rather than variation between different eggs or different cartons.
the aforementioned eggs post-dehydration (but before crushing/powderizing)
The member of the team who prepared the samples had this to say:
Making a “Twinkie puree” out of a bowl of twinkies, and then precisely weighing it out into drying trays and placing it in a dehydrator, is probably the strangest thing I have ever done in the name of science. My trusty stick blender really struggled with twinkies, and I had to take a pause because the overworked motor started to make a burning smell. “Twinkiepuree” has unusual visco-elastic properties which make it worth the effort.
Samples were analyzed in triplicate, and each replicate was done entirely separate (its own digestion and its own analysis of the resulting post-digestion solution). Order was randomized, to minimize the risk of “carry-over” from one analysis to the next.
2.2 Digestion
In the literature, most analyses that found low levels of lithium used digestion by nitric acid. To see if this might be the cause of the differences in results, we decided to compare nitric acid digestion to some other digestion approaches. In the end we settled on two other kinds of digestion: 1) digestion with hydrochloric acid, and 2) “dry ashing”, where samples are burned at high temperatures, then the ash is dissolved in nitric acid.
Dry ashing is a good complement to these acid digestion techniques because while oily foods are very chemically resistant to oxidizers, they are also very flammable. Greasy foods full of hydrocarbon chains that may not perfectly come apart in an acid are likely to be fully broken down by incineration. Incineration causes organic compounds to exit the sample as CO2 gas, but elements like sodium, potassium, magnesium, and lithium are non-volatile and remain behind in the ash.
2.3 Analysis
Both ICP-MS or ICP-OES generate a tiny cloud of high-energy plasma, the “inductively-coupled plasma” of the acronym. And both methods inject a cloud of liquid droplets into that plasma. The difference is that ICP-OES examines the light that is emitted by the plasma as the liquid sample hits it, while ICP-MS examines the actual particles of matter (ions) that are emitted by the plasma as the sample hits it, by directing those ions towards a sensor.
3. Results
The first surprise was that hydrochloric acid digestion visibly failed to digest 6 of the 10 foods. Digestions were clearly incomplete and significant solid matter was still visible after the procedure. The 6 foods were carrots, ketchup, spinach, corn syrup, goji berries, and twinkies. This is an interesting mix since it includes fibrous, sugary, and oily foods, so there’s no obvious trend as to what worked and what didn’t.
Without complete digestion, the measurements we got from ICP-OES couldn’t be expected to be at all accurate. So while we have these results, they probably aren’t meaningful, and we discontinued hydrochloric acid digestion for all other samples.
The main results are all ten foods in four conditions: ICP-MS after HNO3 digestion, ICP-OES after HNO3 digestion, ICP-MS after dry ashing, and ICP-OES after dry ashing.
Little difference was found between the results given by ICP-MS and ICP-OES, other than the fact that (as expected) ICP-MS is more sensitive to detecting low levels of lithium. However, a large difference was found between the results given by HNO3 digestion and dry ashing.
In samples digested in HNO3, both ICP-MS and ICP-OES analysis mostly reported that concentrations of lithium were below the limit of detection. The highest numbers given by this technique were in spinach, which was found to contain about 0.2-0.3 mg/kg lithium, and goji berries, which ICP-MS found to contain up to 1.2 mg/kg lithium.
In comparison, all dry ashed samples when analyzed by both ICP-MS and ICP-OES were found to contain levels of lithium above the limit of detection. Some of these levels were quite low — for example, carrots were found to contain only about 0.1-0.5 mg/kg lithium. But other levels were found to be relatively high. The four foods with the highest concentrations of lithium, at least per these analysis methods, were ground beef (up to 5.8 mg/kg lithium), corn syrup (up to 8.1 mg/kg lithium), goji berries (up to 14.8 mg/kg lithium), and eggs (up to 15.8 mg/kg lithium).
These results are summarized in greater detail in the technical report, and in this figure:
4. Which technique is more accurate?
We think that dry ashing (which gives the higher estimates for lithium) is probably more accurate, and here are some reasons why.
Reason #1: Many water samples contain some lithium, and some water samples contain a lot of lithium — sometimes more than 1 mg/L, and occasionally a lot more than 1 mg/L. Unlike food samples, water samples require no digestion, so measurements of water samples are probably quite accurate.
Most food is grown using water and contains some water [CITATION NEEDED]. It would be strange if food, which is made out of water (plus some other things) always contained less lithium than the water it is made out of. More likely, there’s something else that can interfere with the analysis when foods aren’t completely digested.
Reason #2: The analysis lab we used has a “buy one element, get one free” deal, so for all of the foods we submitted, we requested sodium analysis (Na+) on top of the lithium (Li+). We figured, why not, it doesn’t cost any extra.
If there were something unusual about the lithium analysis, you’d expect sodium to behave differently. Specifically, you’d expect each analytical method to find similar levels of sodium in every food. So we compiled the sodium data and ran the same analysis as lithium. And sure enough, it does. Here’s a comparison of the results for lithium and sodium:
(Note that the y axes are different scales. There is way less lithium than sodium in these foods, so when analyzing lithium we are much closer to the limits of quantitation.)
If you were validating the equivalence of sample prep procedures based on Na+, you’d say “looks good, great agreement between ashing and HNO3 digestion.” This isn’t at all true for Li+. Why? We have no idea. But it further supports the suspicion that Li+ is more slippery for some reason, an excellent comparison that highlights just how strange the lithium results are.
This also seems to rule out various “operator error” explanations. If someone were dropping vials or putting them in the machine backwards or something, you would see weird patterns for both lithium and sodium results. The fact that the sodium results look totally normal suggests that something weird is happening for lithium in particular.
Reason #3: Imagine taking pictures with a camera. If you point the camera at something dark, the resulting picture comes out dark. If you point it at something bright, the resulting picture comes out bright. This is a good sign that the camera is working as intended, and that you’re operating it correctly. If your pictures always come out dark, something is probably wrong. Maybe you forgot to take off the lens cap.
We see something similar in these data. Dry ashing sometimes gives low measurements, like in milk and carrots, which it always found to contain less than 0.6 mg/kg lithium. Dry ashing sometimes gives high measurements, like in eggs and goji berries. There’s a lot of noise, but we know that it can produce numbers both large and small.
In comparison, HNO3 digestion always gives tiny numbers. Most of the time it finds that lithium levels are below the limit of detection. When it does seem to detect an actual amount of lithium, the levels are always low, never above 1.2 mg/kg. These numbers look less like actual estimates and more like a problem with the instrument. A cheap digital camera can’t take a good picture at night, even when it’s working perfectly well.
Reason #4: Several parts of the literature hint that spectroscopy techniques are a bad way to measure lithium in food. These comments are often vague, but it seems like people already have reason to think that these methods underestimate the amount of lithium.
For example, Drinkall et al. (1969) mention that they chose to use AAS (“the Unicam SP90 Atomic Absorption Spectrophotometer, [with] a propane-air flame”) because of their concern about “spectral interference occasioned by elements other than lithium” in spectroscopy techniques.
Manifred Anke, who did more work on lithium levels in food than maybe anyone else, makes this somewhat cryptic comment in his 2003 paper:
Lithium may be determined in foods and biological samples with the same techniques employed for sodium and potassium. However, the much lower levels of lithium compared with these other alkali metals, mean that techniques such as flame photometry often do not show adequate sensitivity. Flame (standard addition procedure) or electrothermal atomic absorption spectrophotometry are the most widely used techniques after wet or dry ashing of the sample. Corrections may have to be made for background/matrix interferences. Inductively coupled plasma atomic emission spectrometry [another name for ICP-OES] is not very sensitive for this very low-atomic-weight element.
We can also point to this article by environmental testing firm WETLAB which describes several potential problems in lithium analysis. “When Li is in a matrix with a large number of heavier elements,” they say, “it tends to be pushed around and selectively excluded due to its low mass. This provides challenges when using Mass Spectrometry.” They also indicate that “ICP-MS can be an excellent option for some clients, but some of the limitations for lithium analysis are that lithium is very light and can be excluded by heavier atoms, and analysis is typically limited to <0.2% dissolved solids, which means that it is not great for brines.” We’re not looking at brines, but digested food samples will also include many heavier atoms and some dissolved solids, and might face similar problems.
The upshot is that various sources say something like, “when testing foods, you have to do everything right or you’ll underestimate the amount of lithium”. We can’t tell exactly what these sources think is the right way to do this kind of analysis, but everyone talks about interference and underestimation, and no one mentions overestimation. This makes us suspect that the lower HNO3 digestion numbers are an underestimation and the higher dry ashing numbers are more accurate.
ICP techniques can detect all the elements from lithium to uranium, which means that lithium is just on the threshold of what can be detected. It wouldn’t be terribly surprising if lithium were an edge case, since it is on the edge of detection for ICP analysis. Interference might push it over the edge of the threshold. And interference would only lead to mistakenly lower measurements, not mistakenly higher measurements. This suggests the higher measurements are more accurate.
Reason #5: There are a few cases where teams have used HNO3 digestion and still report high concentrations of lithium in food, in particular Voica, Roba, and Iordache (2020).
This suggests that maybe there’s some trick to HNO3 digestion that can make it give higher, more accurate results, numbers that are consistent with dry ashing. Maybe these teams know something we don’t.
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All of these are reasons to suspect that the higher dry ashing numbers are more accurate. However, the truth is that at this point, nobody knows.
Given this uncertainty, it could be that neither technique is accurate. The true levels of lithium in these foods might be in between, or could be even higher than what was detected by dry ashing.
Using other analysis techniques like AAS or AES or FAES would be a good way to triangulate between these two conflicting methods. Unfortunately we have not been able to find a lab that offers AAS or other alternative methods of chemical analysis. Can anyone help us?
Accuracy aside, one thing that stands out is that none of these techniques are very precise. For three samples of the same well-blended corn syrup, dry ashing with ICP-OES gives estimates of 0.7155 mg/kg, 1.5892 mg/kg, and 8.1207 mg/kg lithium. HNO3 digestion with ICP-OES generally doesn’t report any lithium at all, but for spinach, it gives estimates of 0.3914 mg/kg, 0.2910 mg/kg, and 0.3595 mg/kg. These are for three identical samples of well-blended spinach. In theory they should be the same! But all four techniques appear to have relatively low precision across the board.
5. What does this mean for analytical chemistry?
Two different analytical techniques gave two very different answers when looking at the exact same samples. This seems like an anomaly worth investigating.
These unusual findings may result from the fact that lithium is the third-lightest element and by far the lightest metal. It’s a real weird ion, so this may just be lithium being lithium. But even so, if the nitric acid completely digests a sample and gives a clear, homogeneous solution, it would seem like there is nowhere for Li+ to hide. From first principles, you’d expect this to work.
It’s also possible that this points to a more consistent limitation of common analytical techniques. Certainly it would be a problem if the techniques we used to estimate mercury in fish, or arsenic in rice, consistently underestimated the concentrations of these metals.
It may be smart to run similar studies to compare analytical techniques for estimating other metals in foods, to make sure there aren’t any other hidden surprises like this one. If work along these lines turns up many similar surprises, well, maybe that means we don’t understand analytical chemistry as well as we think.
6. Next Steps
We would like to test a lot more samples, and get a better sense of how much lithium is in all kinds of different foods.
But before we can do that, we have to figure out this mystery around different analytical techniques. It doesn’t make sense to go out and use one method to test a thousand different foods when we don’t know if that method is at all reliable or accurate.
So first off, we will be trying to figure out which technique is most accurate, and if we can, we’ll also try to figure out why these different analytical techniques give such strikingly different results.
There are a few ways we can do this:
We can add known amounts of lithium to food samples in a spike-in study.
We can also spike-in elements that might be interfering with lithium detection.
We can try other kinds of digestion or other analytical techniques (like AAS) as a tiebreaker, and see if they agree more with the HNO3 numbers or the dry ashing numbers.
Or we can study more samples — it’s possible that a food containing 1000 mg/kg would register above the limit of detection for both techniques.
If you have any other clever ideas, please let us know!
In the meantime, here are some ways you can help:
If you have access to the necessary equipment, please replicate our work. We’ve included all the checks we could think of, but it’s still possible that there was some mistake in our procedure, something backwards about the results. Independent labs should confirm that they get similar results when comparing HNO3 digestion to dry ashing in ICP-MS and ICP-OES analysis.
An even bigger favor would be to extend our work. If you are able to replicate the basic finding, it would be jolly good to tack on some new foods or try some new analytical techniques. Do you have access to AAS for some reason? Wonderful, please throw an egg into the flame for us.
If you’re not an analytical chemist but you are a person of means who is both curious and skeptical, you could conceivably hire a lab to replicate or replicate and extend our work. If you’re interested in doing this, we would be happy to advise.
Thanks again to our anonymous donor, to Sarah Jantzi, and to Whylome for supporting this research.
Finally, thank you for reading!
APPENDIX A: Wait what is the background for this study?
Hello, we are SLIME MOLD TIME MOLD, your friendly neighborhood mad scientists.
We started getting into this question because in our opinion, the evidence suggests that exposure to subclinical doses of lithium is responsible for the obesity epidemic — you can read all about it in Part VII and Interludes C, G, H, and I of our series, A Chemical Hunger.
We also understand that not everyone finds this evidence convincing. That’s ok. Even if you don’t think lithium causes obesity, this project is still important for other reasons: 1) lithium might have other health effects, so 2) we should be able to test food for lithium concentrations so we can know how much we’re consuming and act accordingly. And in general, this looks like it might be a gap in analytical chemistry. We should know how to analyze things; so let’s close that gap.
APPENDIX B: Where is all this lithium coming from?
We’ve already written quite a bit about this, so if you want the full story, you should read those posts: in particular Part VII, Interlude G, Interlude H, and Interlude I of A Chemical Hunger.
But the short version is this. Starting around 1950, people started mining more and more lithium and never looked back, and some of what we mine eventually ends up as contamination. Lithium goes in batteries, which end up in landfills. It also goes in the lithium grease used in cars and other heavy machinery, which ends up in runoff. Deeper aquifers often contain more lithium, so drilling deeper wells may have also increased our exposure.
Graph showing world lithium production from 1900 to 2007, by deposit type and year. The layers of the graph are placed one above the other, forming a cumulative total. Reproduced from USGS.
After our recent post on Lithium in Food, several readers pointed us to a literature on “Total Diet Studies”, or TDS for short.
The TDS approach is pretty intuitive: if you want to study contaminants or residues that people are maybe exposed to through their food, one way to do that is to drive around to a bunch of actual grocery stores and supermarkets, buy the kinds of foods people actually buy and eat, prepare the foods like they’re actually prepared in people’s homes, and then test your samples for whatever contaminants or residues you’re concerned about.
A Total Diet Study (TDS) generally consists of selecting, collecting and analysing commonly consumed food purchased at retail level on the basis of food consumption data to represent a large portion of the typical diet, processing the food as for consumption, pooling the prepared food items into representative food groups, homogenizing the pooled samples, and analysing them for harmful and/or beneficial chemical substances (EFSA, 2011a). From a public health point of view, a TDS can be a valuable and cost effective complementary approach to food surveillance and monitoring programs to assess the presence of chemical substances in the population diet and to provide reliable data in order to perform risk assessments by estimating dietary exposure.
These papers include measurements of trace elements in various foods, and some of them include measurements for lithium. We didn’t find these papers while writing our first review of the levels of lithium in food and drink because these papers aren’t looking for lithium specifically — they’re looking at all sorts of different contaminants and minerals, and lithium just happens to sometimes make the cut.
But anyways, several of these papers do include measurements of lithium in various national food supplies, and they’re strange, because unlike every other source we’ve seen, which all routinely find some foods with more than 1 mg/kg lithium, they find less than 0.5 mg/kg lithium in every single food.
TDS with Li
The oldest TDS study we’ve seen that includes lithium is from 1999 in the United Kingdom, reporting on the UK 1994 Total Diet Study and comparing those results to data from previous UK Total Diet Studies. (The UK TDS has been “carried out on a continuous annual basis since 1966” but it seems like they only started including lithium in their analysis in the 1990s.) They report the mean concentrations of 30 elements (aluminium, antimony, arsenic, barium, bismuth, boron, cadmium, calcium, chromium, cobalt, copper, germanium, gold, iridium, iron, lead, lithium, manganese, mercury, molybdenum, nickel, palladium, platinum, rhodium, ruthenium, selenium, strontium, thallium, tin, and zinc) in 119 categories of foods, combined into 20 groups of similar foods for analysis.
The highest mean concentration of lithium they found in the food categories they examined was an average of 0.06 mg/kg (fresh weight) in fish. They estimated a total exposure of 0.016 mg lithium a day, and an upper limit of 0.029 mg a day, in the British diet at the time. This appears to be substantially less than the amount found in a 1991 sample, which gave an estimate of 0.040 mg lithium a day in the British diet. They explicitly indicate there is no data on lithium in foods (in their datasets) from before 1991.
France conducted a TDS in 2000, and a report all about it was published in 2005. They looked at levels of 18 elements (arsenic, lead, cadmium, aluminium, mercury, antimony, chrome, calcium, manganese, magnesium, nickel, copper, zinc, lithium, sodium, molybdenum, cobalt and selenium) in samples of 338 food items.
The highest mean concentration of lithium they found in the food categories they examined was an average of 0.123 mg/kg in shellfish (fresh matter) and 0.100 mg/L in drinking water. They estimated an average daily exposure of 0.028 mg for adults, with a 97.5th percentile daily exposure of 0.144 mg. They specifically mention, “drinking waters and soups are the vectors contributing most (respectively 25–41% and 14–15%) to the exposure of the populations; other vectors contribute less than 10% of the total food exposure.”
France did another TDS in 2006, with a report published in 2012. This time they looked at Li, Cr, Mn, Co, Ni, Cu, Zn, Se and Mo in 1319 samples of foods typically consumed by the French population.
Similar to the first French TDS, the highest mean concentration of lithium they found in the food categories they examined was an average of 0.066 mg/kg (fresh weight) in shellfish. But the highest individual measurements were found in two samples of sparkling water, with 0.612 mg/kg and 0.320 mg/kg.
New Zealand seems to run a Total Diet Study programme every 4–5 years since 1975, but we’ve only been able to find lithium measurements from this project in a paper from 2019, looking at data from the 2016 New Zealand Total Diet Study. Maybe, like some of the other TDS projects, they only started including lithium testing later on. Anyways, in this paper they looked at 10 elements (antimony, barium, beryllium, boron, bromine, lithium, nickel, strontium, thallium and uranium) in eight composite samples each of 132 food types.
This paper is a little strange, and unlike most of these papers, doesn’t give much detail. They summarize the main findings for lithium as, “the reported concentrations ranged from 0.0007 mg/kg in tap water to 0.54 mg/kg in mussels” and say that the mean overall intake of lithium in New Zealand adults is 0.020–0.029 mg/day.
The most recent TDS that looked at lithium seems to be this 2020 paper, which looks at food collected between October 2016 and February 2017 in the Emilia-Romagna Region in Italy. They looked at levels of fifteen trace elements (antimony, barium, beryllium, boron, cobalt, lithium, molybdenum, nickel, silver, strontium, tellurium, thallium, titanium, uranium, and vanadium) in 908 food and beverage samples from local markets, supermarkets, grocery stores, and community canteens.
The highest concentration of lithium they found in the food categories they examined was in fish and seafood (50th percentile 0.019 mg/kg, IQR 0.010–0.038 mg/kg), and legumes (50th percentile 0.015 mg/kg, IQR 0.006–0.035 mg/kg). They estimate a dietary lithium intake for the region of 0.018 mg/day (IQR 0.007–0.029 mg/day).
So overall, these papers report that lithium levels in foods and beverages never break 0.612 mg/kg, and almost universally keep below 0.1 mg/kg.
How About Those Numbers
We’re skeptical of these numbers for a couple of reasons.
The TDS papers say that all foods and beverages contain less than 1 mg/kg lithium, and that people’s lithium intake is well below 1 mg a day. But this is up against sources like the following, which all find much higher levels (not an exhaustive list):
Bertrand (1943), “found that the green parts of lettuce contained 7.9 [mg/kg] of lithium”
Borovik-Romanova (1965) “reported the Li concentration in many plants from the Soviet Union to range from 0.15 to 5 [mg/kg] in dry material”, in particular listing the levels (mg/kg) in tomato, 0.4; rye, 0.17; oats, 0.55; wheat, 0.85; and rice, 9.8.
Ammari et al. (2011), looked at lithium in plant leaves, including spinach, lettuce, etc. and found concentrations in leaves from 2 to 27 mg/kg DM.
Manfred Anke and his collaborators found more than 1 mg/kg in a wide variety of foods, in multiple studies across multipleyears, up to 7.3 mg/kg on average for eggs.
Schnauzer (2002) reviewed a number of other sources finding average intakes across several locations from 0.348 to 1.560 mg a day.
Five Polish sources from 1995 that a reader recently sent us reported finding (as examples) 6.2 mg/kg in chard, 18 mg/kg in dandelions, up to 470.8 mg/kg in pasture plants in the Low Beskids in Poland, up to 25.6 mg/kg in dairy cow skeletal muscle, and more than 40 mg/kg in cabbage under certain conditions. (These papers aren’t available online but we plan to review them soon.)
It seems like either the measurements from the TDS papers are right, and all foods contain less than 1 mg/kg lithium, or all the rest of the literature is right, and many plants and foods regularly contain more than 1 mg/kg lithium. The alternative, that both of them are right, would mean that the same foods consistently contain less than 1 mg/kg in France and New Zealand while containing more than 1 mg/kg in Germany and Brazil. This seems like the most far-fetched possibility.
There are three strikes against the TDS numbers. First, they’re strictly outnumbered. When five papers from four sources (two of those papers are from France) say one thing and the rest of the literature clearly says another, it’s not a sure thing, but the side with more evidence… well it has more evidence for it.
Second, the TDS studies have a divided focus. They’re not really interested in lithium at all; they’re interested in the local food supply, and lithium just happens to be one of between 9 and 30 different elements they’re testing for. In comparison, pretty much all the other papers are looking at lithium in particular. If we had to guess which kind of team is more likely to mess up this kind of analysis, the team interested in this one particular element, or the team that randomly included the element in the list of several elements they’re testing for, we know which we’d pick. It’s hard to imagine that every team looking for lithium chose the wrong analysis or screwed it up in the same way somehow. It’s easy to imagine that the TDS studies, which measured lithium incidentally, might get some part of the analysis wrong.
It’s kind of like clothing. Ready-made sizes will fit most elements, but if you have an unusual body type (really long arms, really thick neck, etc.) you may have to go to a tailor. And lithium has the most unusual body type of all the solid elements. It wouldn’t be at all surprising if off-the-rack clothes didn’t fit poor little lithium.
uhhhhh spectral analysis
The third thing that’s strange is that there seem to be some internal contradictions within the studies. For example, in the first French TDS study, the lithium levels in water are much higher than lithium levels in things that are made out of water, which seems impossible. The mean lithium level in drinking water is 0.100 mg/kg, but the lithium levels in things that are mostly water are much lower: 0.038 mg/kg in soups, 0.006 mg/kg in coffee, 0.004 in non-alcoholic beverages, 0.003 in alcoholic beverages, and 0.002 in hot beverages. Soup is maybe a little different, but coffee and beverages are mostly water. How can there be fifty times more lithium in plain water than in hot beverages, which are (we assume) mostly water?
For that matter, how can drinking water be the category with the second-most lithium (after shellfish)? Water is the main ingredient in beverages, but it’s also a major ingredient of pretty much every food. Fruits, salads, milk, vegetables, etc. etc. all contain lots of water. Unless there’s some major, universal filtering going on, there should be more lithium in at least some foods than there is in water.
And that’s what you see if you look at the other elements in this first French paper — more in foods than in water. For example, the average level of manganese in drinking water in these data is 0.19 mg/kg, and the mean levels in beverages are all 0.30 mg/kg or higher; the mean level in soup is 0.97 mg/kg; the mean level in fruits is 2.05 mg/kg, much higher. Same for zinc. The mean level in drinking water is 0.05 mg/kg, which is the lowest mean level of zinc of any food category. Other elements, at least, tend to have higher concentrations in some foods than in water.
In the second French TDS study, the same thing happens. The highest concentration of lithium they found in any food was in water, 0.612 mg/kg. The mean for water this time around was only 0.035 mg/kg, but that’s still higher than the means for most beverages and the mean for almost every food.
(The other TDS papers don’t give mean lithium measurements for water, so we can’t do the same comparison with them.)
This doesn’t make much sense. Water is a major component of many foods and it would be shocking if lithium didn’t find its way from water into food (and more obviously into beer and tea). But all of the fruits and vegetables have less lithium than the water that would presumably be used to irrigate them.
There’s a rich literature of hydroponics experiments that shows that all sorts of plants accumulate lithium. When you grow them in a lithium solution under controlled conditions, or in soil spiked with lithium, the plants end up containing a higher concentration of lithium than the solution/soil they were grown in.
These spikes are much larger than the levels of lithium plants are normally exposed to in the environment, but they’re experimental evidence that lithium accumulates, even to enormous degrees. You should reliably expect to see more lithium in plants than in the water they’re grown with. There might be some plants that don’t accumulate, but water shouldn’t universally contain the highest amounts.
We didn’t really include these sources in our original review because that was a review of lithium in food, and these hydroponically-grown experimental plants aren’t in the actual food supply. But they’re pretty informative, so here’s a selection of the studies:
Magalhães et al. (1990) grew radish, lettuce and watercress in a hydroponic system, with solution containing lithium levels of 0.7, 6.8 and 13.6 mg/L. These are all somewhat high, but exposure to 0.7 mg/L in water isn’t totally unrealistic. Plants were collected thirty days after transplanting. At the lowest and most realistic level of exposure, 0.7 mg/L, lettuce contained 11 mg/kg lithium, radish bulbs contained 11 mg/kg, radish leaves contained 17 mg/kg, and watercress contained 37 mg/kg. At 6.8 mg/L in the solution all plants contained several hundred mg/kg, and at 13.6 mg/L, radish leaves and watercress contained over 1000 mg/kg.
Hawrylak-Nowak, Kalinowska, and Szymańska (2012) grew corn and sunflower plants in glass jars containing 0 (control), 5, 25, or 50 mg/L lithium in a nutrient solution. After 14 days, they harvested the shoots, and found that lithium accumulated in the shoots in a dose-dependent manner. Even in the control condition, where no lithium was added to the solution, sunflower shoots contained 0.9 mg/kg and corn shoots contained 4.11 mg/kg lithium. At 5 mg/L solution, sunflower contained 422.5 mg/kg and corn contained 72.9 mg/kg; at 25 mg/L solution, sunflower contained 432.0 mg/kg and corn contained 438.0 mg/kg; at 50 mg/L solution, sunflower contained 3,292.0 mg/kg and corn contained 695.0 mg/kg. These levels are unrealistically high, but the example is still illustrative.
Kalinowska, Hawrylak-Nowak, and Szymańska (2013) grew lettuce hydroponically in solution containing 0, 2.5, 20, 50 or 100 mg/L lithium. Lithium concentrations above 2.5 mg/L progressively fucked the plants up more and more, but there was clear accumulation of lithium in the lettuce. There was some concentration in the leaves in a solution of 2.5 mg/L (though they don’t give the numbers), and when the lettuce was grown in a 20 mg/L solution, there was around 1000 mg/kg in the leaves.
Antonkiewicz et al. (2017) is an unusual paper on corn being grown hydroponically in solutions containing various amounts of lithium. They find that corn is quite resistant to lithium in its water — it actually grows better when exposed to some lithium, and only shows a decline at concentrations around 64 mg/L. (“The concentration in solution ranging from 1 to 64 [mg/L] had a stimulating effect, whereas a depression in yielding occurred only at the concentrations of 128 and 256 [mg/L].”) But the plant also concentrates lithium — even when only exposed to 1 mg/L in its solution, the plant ends up with an average of about 11 mg/kg in dry material.
Robinson et al. (2018) observed significant concentration in the leaves of several species as part of a controlled experiment. They planted beetroot, lettuce, black mustard, perennial ryegrass, and sunflower in controlled environments with different levels of lithium exposures. “When Li was added to soil in the pot experiment,” they report, “there was significant plant uptake … with Li concentrations in the leaves of all plant species exceeding 1000 mg/kg (dry weight) at Ca(NO3)2-extractable concentrations of just 5 mg/kg Li in soil, representing a bioaccumulation coefficient of >20.” For sunflowers in particular, “the highest Li concentrations occurred in the bottom leaves of the plant, with the shoots, roots and flowers having lower concentrations.”
Again, these are unrealistic for the amount of lithium you might find in your food, but they’re clear support for the idea that plants consistently accumulate lithium relative to the conditions they’re grown in. It doesn’t make sense that we see water having the highest concentration in the TDS data.
This is your sunflower leaf on 50 mg/L lithium
So for all these reasons, we’re pretty sure that the TDS numbers are wrong and that the lithium-specific literature is right. Specialty research that looks for lithium in particular is more reliable in our opinion than sources that happen to look at lithium as one contaminant along with a dozen others.
But even so, you’d have to be terminally incurious to look at this and not wonder what was going on. Why do these five papers have measurements that don’t match the rest of the literature?
What’s Going on in the TDS
Since these papers disagree with every other source, and they all share the same Total Diet Study approach, it seems like there must be something wrong with that approach.
Sometimes this kind of mistake can come from problems with the equipment, dropping a decimal, or misreading units, like mistaking mg/kg for µg/kg.
But we have a hard time imagining that all of these different teams with (as far as we can tell?) no overlap in authors would be making exactly the same error of using the wrong units or moving a decimal place. It’s possible they all use the same slightly-misleading software or something; we have seen a few other papers that report lithium in one set of units, and every other element they test for in different units. But again, it would be weird for every single TDS study to screw this up in exactly the same way.
So we went back and took a closer look at their methods. What we noticed is that every one of these TDS studies used the same analysis technique — inductively coupled plasma mass spectrometry, or ICP-MS.
So we wonder if there might be an issue with ICP-MS.
Samples of each food group … were homogenized and digested (0.5 g) in inert plastic pressure vessels with nitric acid (5 ml) using microwave heating (CEM MDS 2000 microwave digestion system). All elements except mercury, selenium and arsenic were analysed by Inductively Coupled Plasma-Mass Spectrometry (ICP-MS) (Perkin Elmer Elan 6000).
The elementary analyses (about 18 000 results in all) were carried out by the Environmental Inorganic Contaminants and Mineral Unit of the AFSSA-LERQAP, which is the national reference laboratory. All the 998 individual food composite samples were homogenized and digested (about 0.6 g taken from each sample) in the quartz vessels with suprapure nitric acid (3 ml) using Multiwave closed microwave system (Anton-Paar, Courtaboeuf, France). The total content of all selected essential and non essential trace elements in the foods was determined by Inductively Coupled Plasma-Mass Spectrometry (ICP-MS) (VG PlasmaQuad ExCell-Thermo Electron, Coutaboeuf, France), a very powerful technique for quantitative multi-elemental analysis.
The National Reference Laboratory (NRL) for heavy metals was chosen to analyse 28 trace elements, and among them nine essential elements, Li, Cr, Mn, Co, Ni, Cu, Zn, Se and Mo, by inductively coupled plasma-mass spectrometry (ICP-MS) after microwave-assisted digestion.
…
Sample digestion was carried out using the Multiwave 3000 microwave digestion system (Anton-Paar, Courtaboeuf, France), equipped with a rotor for 8 type X sample vessels (80-mL quartz tubes, operating pressure 80 bar). Before use, quartz vessels were decontaminated in a bath of 10% HNO3 (67% v/v), then rinsed with ultra-pure water, and dried in an oven at 40 °C. Dietary samples of 0.2–0.6 g were weighed precisely in quartz digestion vessels and wet-oxidised with 3 mL of ultra-pure water and 3 mL of ultra-pure HNO3 (67% v/v) in a microwave digestion system. One randomly-selected vessel was filled with reagents only and taken through the entire procedure as a blank. The digestion program had been optimised previously (Noël, Leblanc, & Guérin, 2003). After cooling at room temperature, sample solutions were quantitatively transferred into 50-mL polyethylene flasks. One hundred microlitres of internal standard solution (1 mg L−1) were added, to obtain a final concentration of 2 μg L−1, and then the digested samples were made up with ultrapure water to the final volume before analysis by ICP-MS.
ICP-MS measurements were performed using a VG PlasmaQuad ExCell (Thermo, Courtaboeuf, France). The sample solutions were pumped by a peristaltic pump from tubes arranged on a CETAC ASX 500 Model 510 autosampler (CETAC, Omaha, NE).
We measured content of fifteen trace elements (antimony, barium, beryllium, boron, cobalt, lithium, molybdenum, nickel, silver, strontium, tellurium, thallium, titanium, uranium, and vanadium) in 908 food and beverage samples through inductively coupled plasma mass spectrometry.
…
Using a clean stainless-steel knife, we cut solid foods by collecting samples from six different points in the plate. Then, we homogenized the samples using a food blender equipped with a stainless-steel blade and we placed a portion of 0.5 g in quartz containers previously washed with MilliQ water (MilliQPlus, Millipore, MA, USA) and HNO3. We liquid-ashed the samples with 10 ml solution (5 ml HNO3 + 5 ml·H2O) in a microwave digestion system (Discover SP-D, CEM Corporation, NC, USA) and we finally stored them in plastic tubes, and diluted to 50 ml with deionized water before analysis. Using an inductively coupled plasma mass spectrometer (Agilent 7500ce, Agilent Technologies, CA, USA), we performed trace element determination.
So, all of these papers use the same analysis technique, ICP-MS. We don’t know the exact technique used by the team in New Zealand, but all the other teams used microwave digestion with nitric acid (HNO3). Three of them (the French and Italian TDS studies) used quartz vessels.
The fact that all these studies use similar analysis techniques makes it much more plausible that something about this technique is screwing up something about the lithium detection.
This also seems likely because most other papers, the ones that find more than 1 mg/kg lithium in food, don’t use ICP-MS. Here’s a small selection.
The most recent paper finding more than 1 mg/kg lithium in plant matter seems to have used inductively coupled plasma optical emission spectrometry (ICP-OES), a related but distinct technique. This is Robinson et al. (2018), which found that plants can contain “several hundred mg/kg Li” in leaves. Here’s their procedure:
Plant samples were washed in deionized water and dried at 60 °C until a constant weight was obtained. Subsequently, they were milled using a Cyclotech type 1093 cyclone grinder with an aluminium rotor. Plant material (0.5 g) was digested in 5 ml HNO3. The digests were diluted with Milli Q (Barnstead, EASYpure RF, 18.3 MΩ-cm) to a volume of 25 ml and filtered with a Whatman 52 filter paper (pore size 7 μm). … Pseudo-total element concentrations (henceforth referred to as “total”) were determined in the acid digests using ICP-OES (Varian 720 ES).
Ammari et al. (2011), looked at lithium in solids (plant leaves, including spinach, lettuce, etc.) and found concentrations in leaves from 2 to 27 mg/kg DM. They used this procedure:
Collected leaves were gently washed in distilled water, air-dried, and then oven-dried to a constant weight at *70°C. Dry leaves were finely ground in a Moulinex Mill (Moulinex, Paris, France) to pass through a 40-mesh sieve. As Li is known to be present in cell vacuoles in inorganic soluble form, Li was determined in filtrates of oven-dry ground leaf samples (5 g) suspended in 50 ml of deionized water for 1 h. This procedure was used in the current study because not all the lithium present in natural unprocessed foods is taken up by the human body (pers. comm. with nutritionists; Dr. Denice Moffat, USA). Lithium extracted with deionized water represents the soluble fraction that is directly taken up by the gastrointestinal tract and considered the most bio-available. … The concentration of Li in leaf samples was measured with a flame photometer.
Anke’s 2005 paper doesn’t give a ton of detail, but seems to have used atomic absorption spectroscopy (AAS) for lithium, and reports numbers up to 7.5 mg/kg in foods.
Magalhães et al. (1990) found up to 1,216 mg/kg in (hydroponically-grown, experimental) watercress and say:
Thirty days after transplanting, the plants were harvested, shoots and roots separately, and their fresh weight determined. They were oven-dried at 700C for 72 hours, weighted, ground in a Wiley mill and analyzed for N, P, K, Ca, Mg, Fe and Li contents after digestion in H2SO4 and H202. N was determined by Nesslerization, P by an ammonium molybdate-amino naphthol sulfonic acid reduction method (Murphy & Riley 1962), K and Li by flame emission and Ca, Mg and Fe by atomic absorption (Sarruge & Haag 1974).
Drinkall et al. (1969), one of our oldest sources, found up to 148 mg/kg in pipe tobacco and used “the atomic absorption technique”. Specifically they say:
Methods for determination of lithium in foodstuffs have in the past been limited almost entirely to the use of the spectrograph and the flame photometer. In the present investigation, however, it was decided to apply the technique of atomic absorption for this purpose. The chief reason for this choice was the lack of occurrence of spectral interference occasioned by elements other than lithium, Indeed, the only elements which were thought likely to prove troublesome were calcium and strontium. Even these, however, were found not to interfere. The instrument used throughout this work was the Unicam SP90 Atomic Absorption Spectrophotometer, a propane-air flame being employed.
So this diverse set of methods all found levels of lithium above 1 mg/kg, while the “ICP-MS with microwave digestion in nitric acid (usually in quartz vessels)” technique seems to reliably find way less than 1 mg/kg. This is starting to look like it’s an issue with the analysis.
If this is the case, then if we can find other papers that use ICP-MS with microwave digestion in nitric acid, they should also show low levels of lithium, well below 1 mg/kg.
That’s exactly what we’ve found. Take a look at Saribal (2019). This paper used ICP-MS and looked at trace element concentrations in cow’s milk samples from supermarkets in Istanbul, Turkey. They found an average of 0.009 mg/L lithium in milk, way lower than the measurements for milk found in sources that don’t use ICP-MS.
Saribal, like the TDS studies, used ICP-MS to look for lithium alongside a huge number of other elements — 19 in fact. The full list was: lithium, beryllium, chromium, manganese, cobalt, nickel, copper, arsenic, selenium, strontium, molybdenum, cadmium, antimony, barium, lead, bismuth, mercury, thallium, and uranium. Like the TDS studies, they did digestion in nitric acid:
The quadrupole inductively coupled plasma mass spectrometer (ICP-MS) used in this work was Thermo Scientific X Series II (Thermo Fisher Scientific, Bremen, Germany).
…
One-milliliter portions of each milk samples were digested in 65% HNO3 and 2 mL 30% H2O2 (Merck, Poole, UK) on a heat block. The temperature was increased gradually, starting from 90 °C and increasing up to 180 °C. The mixture was cooled down and the contents were transferred to polypropyl- ene tubes with seal caps. Each digested sample was diluted to a final volume of 10 mL with double deionized water
Here’s another one. Kalisz et al. (2019) looked at “17 elements, including rare earth elements, in chilled and non-chilled cauliflower cultivars”. They used ICP-MS, they microwave digested with nitric acid, and they found lithium levels of less than 0.060 mg/kg. Here’s the method:
We investigated the content of Ag, Al, Ba, Co, Li, Sn, Sr, Ti, Sb, and all rare-earth elements. … Curds were cut into pieces and dried at 70 °C in a dryer with forced air circulation. Then, the plant material was ground into a fine and non-fibrous powder using a Pulverisette 14 ball mill (Fritsch GmbH, Germany) with a 0.5-mm sieve. Next, 0.5 g samples were placed in to 55 ml TFM vessels and were mineralized in 10 ml 65% super pure HNO3 (Merck no. 100443.2500) in a Mars 5 Xpress (CEM, USA) microwave digestion system. The following mineralization procedure was applied: 15 min. time needed to achieve a temperature of 200 °C and 20 minutes maintaining this temperature. After cooling, the samples were quantitatively transferred to 25 ml graduated flasks with redistilled water. Contents of mentioned elements were determined using a high-dispersion inductively coupled plasma optical emission spectrometer (ICP-OES; Prodigy Teledyne Leeman Labs, USA).
There are a couple complications, but they’re worth looking at. Seidel et al. (2020) used ICP-MS and found reasonable-seeming numbers in a bunch of beverages. But, as far as we can tell, they didn’t digest the beverages at all. They just say:
Li concentrations in our 160 samples were determined via inductively coupled plasma mass spectrometry (ICP-MS) as summarized in Table 1.
Here’s Table 1 in case you’re curious:
This seems like evidence that something about the digestion process might be to blame.
There’s also Voica, Roba, and Iordache (2020), a Romanian paper which used ICP-MS and found up to 3.8 mg/kg in sheep’s milk and up to 4.2 mg/kg in pumpkins. This is pretty surprising — it’s the first ICP-MS paper we’ve seen that finds more than 1 mg/kg lithium in a sample of food. They even use microwave digestion with nitric acid! So at first glance, this looks like a contradiction — but when we looked closer, their method did differ in some interesting ways.
The lithium concentrations were determined by inductively coupled plasma – mass spectrometry (ICP-MS).
…
Considering that samples have a very complex composition with large organic matter content, the total digestion of the matrix is mandatory to assure complete metal solubility. The studied samples were subjected to microwave assisted nitric acid digestion by using a closed iPrep vessel speed system MARS6 CEM One Touch. The digestion vessels were cleaned with 10 mL HNO3 using the microwave cleaning program and rinsed with deionized water. Approximately 0.3 g aliquots of the samples were weighed, followed by digestion in 10mL HNO3 60% at high pressure, temperature and in the presence of microwave irradiation. The vessel was closed tightly, placed on the rotor, and the digestion was carried out following the program presented in Table 1.
After complete digestion and cooling, the samples were filtered, transferred to 50 mL graduated polypropylene tubes and diluted to volume with deionized water.
A Perkin Elmer ELAN DRC-e instrument was used with a Meinhard nebulizer and a glass cyclonic spray chamber for pneumatic nebulization. The analysis was performed in the standard mode and using argon gas (purity ≥ 99.999%) for the plasma following the manufacturer’s recommendations.
The operating conditions were a nebulizer gas flow rate of 0.92 L/min; an auxiliary gas flow of 1.2 L/min; a plasma gas flow of 15 L/min; a lens voltage of 7.25 V; a radiofrequency power of 1100 W; a CeO/Ce ratio of 0.025; and a Ba++/Ba+ ratio of 0.020.
We don’t know exactly what the difference might be, but the fact that they mention that “considering that samples have a very complex composition with large organic matter content, the total digestion of the matrix is mandatory to assure complete metal solubility” suggests that they were aware of limitations of normal digestion methods that other teams may have been unaware of. And none of the other papers seem to have used pneumatic nebulization, so maybe that makes the difference and lets you squeeze all the lithium out of a pumpkin.
yeah that’s one way to do it
Another difference we notice is that while Voica, Roba, and Iordache do use ICP-MS and the same kind of digestion as the TDS studies, they don’t test for anything else — they’re just measuring lithium. So maybe the thing that torpedoes the ICP-MS measurements is something about testing for lots of elements at the same time — a trait shared by all the TDS studies, Saribal (2019), and Kalisz et al. (2019), but not by Seidel et al. (2020) (the beverages paper) and not by Voica, Roba, and Iordache (2020).
A final (we promise) paper that helps triangulate this problem is Nabrzyski & Gajewska (2002), which looked at lithium in food samples from Gdańsk, Poland. They found an average of only 0.07 mg/kg in milk products and of only 0.11 mg/kg in smoked fish. This is not quite as low as the TDS studies but it’s much lower than everything else. And weirdly, they didn’t use ICP-MS, they used AAS. But they did digest their foods in nitric acid. Here’s the method:
The representative samples were dry ashed in quartz crucibles and the ash was treated with suitable amounts of conc. HCl and a few drops of conc. HNO3. The obtained sample solution was then used for the determination of Sr, Li and Ca by the flame atomic absorption spectrometry (AAS) method. Ca and Li were determined using the air-acetylene flame and Sr with nitrous oxide-acetylene flame, according to the manufacturer’s recommendations.
So maybe this seems like more evidence that it’s something about the digestion process in particular, though this paper could also just be a weird outlier. It’s hard to tell without more tests.
Close Look at ICP-MS
We seem to have pretty clear evidence that ICP-MS, maybe especially in combination with microwave digestion / digestion with nitric acid, gives much lower numbers for lithium in food samples than every other analysis technique we’ve seen.
So we wanted to know if there was any other reason to suspect that ICP-MS might give bad readings for lithium in particular. We did find a few things of interest.
If you check out the Wikipedia page for ICP-MS, lithium is mentioned as being just on the threshold of what the ICP-MS can detect. This makes sense because lithium is unusual, much smaller than all other other metals. See for example: “The ICP-MS allows determination of elements with atomic mass ranges 7 to 250 (Li to U)” and “electrostatic plates can be used in addition to the magnet to increase the speed, and this, combined with multiple collectors, can allow a scan of every element from Lithium 6 to Uranium Oxide 256 in less than a quarter of a second.”
While ICP-MS is generally considered the gold standard for spectral analysis, like all methodologies, it has some limitations. Given that lithium is at the bottom of the range to begin with, it seems plausible to us that even small irregularities in the analysis might push it “off the end” of the range, disrupting detection. There’s more likely to be problems with lithium than with the other elements the TDS papers were analyzing.
We noticed that the 1999 UK TDS study had this to say about the upper limits of detection for ICP-MS: “The platinum group elements are notoriously difficult to analyse, as the concentrations, generally being close to the limits of detection, can be prone to some interferences in complex matrices when measured by ICP-MS.”
Now lithium is on the low end of the range, not the high range. But since the UK TDS study authors were concerned that elements “close to the limits of detection, can be prone to some interferences in complex matrices when measured by ICP-MS”, it seems like interference might be an issue. This shows that “fall of the end of the range” is a real concern with ICP-MS analysis. So ICP-MS may be the gold standard for spectral analysis, but it falls short of being the platinum standard.
There’s also something interesting in Anke’s 2003 paper, where he says:
Lithium may be determined in foods and biological samples with the same techniques employed for sodium and potassium. However, the much lower levels of lithium compared with these other alkali metals, mean that techniques such as flame photometry often do not show adequate sensitivity. Flame (standard addition procedure) or electrothermal atomic absorption spectrophotometry are the most widely used techniques after wet or dry ashing of the sample. Corrections may have to be made for background/matrix interferences. Inductively coupled plasma atomic emission spectrometry is not very sensitive for this very low-atomic-weight element.
As usual with Anke this is very cryptic, and inductively coupled plasma atomic emission spectrometry (ICP-AES) isn’t the same technique as ICP-MS. But even so, Anke’s comment does suggest that there might be some limitations on ICP methods when measuring lithium, that they might not be very sensitive.
We also found an article by environmental testing firm WETLAB which describes several problems you can run into doing lithium analysis, including that “[w]hen Li is in a matrix with a large number of heavier elements, it tends to be pushed around and selectively excluded due to its low mass. This provides challenges when using Mass Spectrometry.” They also indicate that “ICP-MS can be an excellent option for some clients, but some of the limitations for lithium analysis are that lithium is very light and can be excluded by heavier atoms, and analysis is typically limited to <0.2% dissolved solids, which means that it is not great for brines.” We’re not looking at brines, but this may also hold true for digested food samples. WETLAB indicates their preferred methodology is ICP-OES.
Conclusion
Maybe nobody knows what’s going on here! It’s looking more and more like this is just a question that’s sitting out on the limits of human knowledge. It’s a corner case — to know why some papers find high levels and other papers find really low levels, you might have to jointly be an expert on ICP-MS, lithium analysis, and chemical analysis in food. Manfred Anke is the only guy we’ve ever heard of who seemed like he might be all three, and he’s been dead for more than ten years. So maybe there’s no one alive who knows the answer. But that’s why we do science, right?
In any case, we’re very glad to know about this complexity early on in the process of planning our own survey, since we had also been planning to use ICP-MS! We had assumed that ICP-MS was the best technique and that it would certainly give us the most accurate numbers. But measurement is rarely that simple — we should have been more careful, and now we will be.
How do we figure out what’s going on here, and what technique we should use? We could go back and pore over the literature in even more detail. But that would take a long time, and would probably be inconclusive. Much better is to simply test a bunch of foods using different techniques, pit ICP-MS against techniques like AAS and flame photometry, and see if we can figure out what’s going on. So that’s what we’re gonna do.
SLIME MOLD TIME MOLD 