[PART I – MYSTERIES]
[PART II – CURRENT THEORIES OF OBESITY ARE INADEQUATE]
[PART III – ENVIRONMENTAL CONTAMINANTS]
[INTERLUDE A – CICO KILLER, QU’EST-CE QUE C’EST?]
[PART IV – CRITERIA]
[PART V – LIVESTOCK ANTIBIOTICS]
[INTERLUDE B – THE NUTRIENT SLUDGE DIET]
[PART VI – PFAS]
[PART VII – LITHIUM]
[INTERLUDE C – HIGHLIGHTS FROM THE REDDIT COMMENTS]
[INTERLUDE D – GLYPHOSATE (AKA THE ACTIVE INGREDIENT IN ROUNDUP)]
[INTERLUDE E – BAD SEEDS]
[PART VIII – PARADOXICAL REACTIONS]
[PART IX – ANOREXIA IN ANIMALS]
[INTERLUDE F – DEMOGRAPHICS]
[INTERLUDE G – Li+]

A while back, one of us was talking to a family member about the improperly sealed abandoned boreholes in the Gila River Valley, and how oilfield brines are really high in lithium. This inspired him to speculate that while most of us don’t live near improperly sealed abandoned boreholes, there is a different kind of hole in the ground that many of us interact with every day — the wells we draw our water from.

There are a couple of things that make water wells seem kind of suspicious. When it comes to obesity, we’re looking for something that’s really universal, something that would reach pretty much everyone, because every part of the world is becoming more obese all the time. Maybe some people have oilfield brines in their water, sure. But not everyone is downriver from a pipeline.

Well, back in the day, nobody got their water from deep, drilled wells. Nowadays, millions of people drink well water every single day. The USGS estimates that 115 million people, more than one-third of the nation’s population, rely on groundwater for drinking water, and that 43 million of those people are drinking from private wells. And just because you aren’t drinking well water doesn’t mean you’re not affected — when all those wells bring up water from the depths, it ends up mixing with the surface water. 

This could represent a pretty big change in the ecosystem. You might think of groundwater as just normal water — maybe more pure, but still just water. But often it’s not like surface water at all. Some of the water flowing underground has been there only for a few weeks, but some of that water has been down there for hundreds, thousands, or even millions of years. 

Generally speaking, the deeper the well, the older the water you’re drawing. But sometimes even relatively shallow wells draw from very old waters. For example, this analysis from Alberta suggests that in the Paskapoo Formation aquifers, “a very important source of water for irrigation and drinking in southwestern Alberta,” some water samples drawn from relatively shallow depths (less than 60 meters) are more than 1,000,000 years old.

Who knows what might be down there. The USGS helpfully notes, “old groundwater is more likely than young groundwater to have contaminants from natural sources, such as metals and radionuclides, because old groundwater can spend thousands of years in contact with and reacting with aquifer rocks and minerals that might contain these elements.” If water from drilled wells tends to have more lithium in it than water from shallow wells or surface water does, that would explain why people are exposed to more lithium now than they used to be, and could explain why the exposure is so universal. 

Basic well-drilling technology first arose in the early 1800s. We can take as an example Levi Disbrow, who according to some sources drilled the first artesian well in the United States in 1824. Things took a leap forward in 1909 when a patent for the first roller cone drill bit was issued to Howard Hughes Sr. — but even then, drilling tools were all still platform-based, and impractical for homeowners. It wasn’t until the 1940s that portable drills became effective, and it took until the 1970s for drilled wells to become common for individual homes. 

Most states keep pretty good records for drilled wells, so we’re able to confirm this with publicly available data. Rather than trying to hunt down data for every state, we did some spot checks. For example, Massachusetts keeps a database of wells dating back to 1962. Looking just at new, domestic wells, we see that about 96% were drilled in 1970 or later, and about 91% were drilled in 1980 or later. The two biggest decades for domestic drilling in Massachusetts were the 1990s and the 2000s, when about 37,000 wells were drilled each decade.

In Vermont, well drillers have been required to submit reports to the state on each well they drill since 1966, but there are some records dating as far back as 1924. We found that of the wells in the database, 96% had been drilled since 1970, and 83% had been drilled since 1980. Again, the two decades with the most well drilling were the 1990s and 2000s.

Since we mentioned bioaccumulation in plants last time, we also want to mention that a lot of crops these days are irrigated with water from drilled wells. Without getting too much into the details, it looks like most irrigation wells were also drilled pretty recently. In Kansas for example, it looks like only five of the irrigation wells on record were drilled before 1970, compared to about 22,000 wells drilled afterwards! 

The timeline for drilled wells lines up pretty well with the timeline for the spread of obesity. These days lots of people get their water from drilled wells, but that’s historically weird. If well water contains more lithium than surface water does, and lithium causes obesity, that would explain why obesity is so widespread.

The second reason this seems plausible is that similar things have happened with well-drilling and other contaminants. Let’s look at one well-documented example (h/t Phil Wagner):

It was the best intentions of governments and world bodies in the 1970s to improve health that led to the crisis in Bangladesh. Until the 1980s, most villagers drew water from shallow wells, or collected it from ponds and rivers – and regularly suffered cholera, dysentery and other water-borne diseases. 

In response to these preventable illnesses, the UN and many western donors advised Bangladesh to bore deeper “tube wells” into the underground water aquifers to draw clean, pathogen-free water. But the scientists and donors advised drilling to about 150ft (46m) – almost precisely the depth of arsenic-rich rock. 

The first cases of arsenic poisoning were discovered in the early 1990s, and, in 1995, an international conference in Kolkata drew the world’s attention to the problem.

Efforts have been made to do something about this, but it still seems to be a huge problem. This report from the Human Rights Watch in 2016 says that “an estimated 43,000 people die each year from arsenic-related illness in Bangladesh”.

Similar contamination can be found elsewhere. In parts of India, wells are contaminated with uranium.

Third and finally, we want to point to a few examples that indicate that lithium specifically might be a problem in deep, drilled wells. The first is a passage from Sievers & Cannon (1973), the Gila River Valley paper, about where the Pima got their home drinking water:

Wells, the main source of domestic water, have needed deepening because the ground-water table has dropped at least 20 feet in the last few years. The lower aquifers now in use produce water of higher salt content than previously.

They don’t quite say it outright, but this suggests that the Pima wouldn’t have been exposed to as much lithium if they hadn’t deepened their wells. The lower aquifers have a higher salt content, and this likely includes dissolved lithium salts.

An even clearer example can be found in this paper about lithium levels in part of Maryland in 1976, where they found that deep wells had abnormally high levels of lithium compared to other sources: 

Lithium levels varied by type of water source. The highest lithium levels were found in deep wells. Two thirds of the samples with concentrations greater than or equal to 10 [ng/mL] were found in deep wells, and 24% of the deep wells had concentrations greater than or equal to 10 [ng/mL]. City waters had no levels greater than 12 [ng/mL], and less than 2% had levels over 10 [ng/mL].

This all just makes the idea seem plausible. What we really want to know is, is there an appreciable amount of lithium in well water today? 

Lithium in Modern America

The answer is yes!

The first time we wrote about lithium, we said we didn’t know if there was lithium in the groundwater, we didn’t know if groundwater concentrations of lithium had increased over time, and the USGS wasn’t interested. Well, we are happy to report that all of that has changed.

On February 11, 2021, the USGS released a report titled Lithium in U.S. Groundwater. The first conclusion they share is that “45% of public-supply wells and about 37% of U.S. domestic supply wells have concentrations of lithium that could present a potential human-health risk.” It doesn’t get any better from there. The header for the report looks like this:

The report is backed by a paper released on May 1, 2021. The raw data is available here (see the two urls near the bottom).

There’s a lot of interesting stuff in this paper, but mostly we want to know if there are serious levels of lithium in well water, and if most Americans are getting lithium in their drinking water. The answer in both cases seems to be a pretty clear “yes”:

Concentrations nationwide ranged from <1 to 396 [ng/mL] (median of 8.1 [ng/mL]) for public supply wells and <1 to 1700 [ng/mL] (median of 6 [ng/mL]) for domestic supply wells. For context, lithium concentrations were compared to a Health Based Screening Level (HBSL, 10 [ng/mL]) and a drinking-water only threshold (60 [ng/mL]). These thresholds were exceeded in 45% and 9% of samples from public-supply wells and in 37% and 6% from domestic-supply wells, respectively

This dataset includes a few samples from as far back as 1991, but almost all the samples were collected after 2000, and the biggest chunk are all from 2010 or later, so this is a pretty modern dataset. As we can see, the median concentration in well water is about 6-8 ng/mL, though this kind of obscures the fact that about 40% of all wells contain more than 10 ng/mL of lithium. Since we have the raw data, we can clarify and state that the median for all samples was 6.9 ng/mL. 

There are two comparisons we want to make. The first is to historical sources — are we being exposed to more lithium now than we were back in the day? Our best source for this is that 1964 paper, Public water supplies of the 100 largest cities in the United States by Durfor & Becker, which as you may remember is available on Google Books. They report a median level lithium concentration of only 2.0 ng/mL in the water supplies they analyzed. Based on this, the median level in US drinking water seems to have increased 3-4x since 1964. But this obscures the long tail of these data. Back in 1964, the maximum level they recorded was 170 ng/mL. In the modern data, the highest level is 1700 ng/mL, 10x higher.

We can also compare this to the Pima, who in the early 1970s were being exposed to about 100 ng/mL of lithium in their drinking water. This was very unusual back then but it is only somewhat unusual now — about 5% of the modern well water samples were in this range or higher, and about 1% contained more than 200 ng/mL. 

The median level of contamination has increased somewhat, but the maximum level of exposure has increased by an order of magnitude. There’s definitely more lithium in the groundwater today than there was in the 1960s and 1970s.

(We also noticed that in this paper, they mention: “As the stream flows toward its mouth, many sources contribute dissolved and suspended matter to the stream. … It is not surprising that the raw water obtained by Minneapolis, Minn., from the upper reaches of the Mississippi River contains about one-half the amount of dissolved solids as the raw water used by New Orleans, La., near the mouth of the river.”)

The other comparison we want to make is to other countries. The United States is pretty obese, much more obese than most other parts of the world. So the next step is to track down some data and see if other parts of the world have more or less lithium in their groundwater and/or drinking water than we do. 

We’ve found sources for a couple other countries, and we’re prepared to make some comparisons. These distributions are generally skewed, so the median is really the most appropriate metric here — but unfortunately some of these sources don’t report it and just report the mean instead. So to keep us comparing apples to apples as much as possible, remember — the US is about 36% obese, the median of lithium in the well water dataset is 6.9 ng/mL, and the mean is 19.7 ng/mL.

Greece is about 25% obese. In 2013, a team published this paper looking at lithium levels in 149 samples of drinking water from 34 prefectures of Greece. They found that the average level of lithium in the samples was 11.10 ng/mL, with a range from 0.1 to 121 ng/mL. (They also looked at 21 samples of different kinds of bottled waters and found mean lithium levels of 6.21 ng/mL) We can see that the average is lower than the average level in American well water, and that while there is quite a range of values, the range is also much more limited than the range in modern American water samples. We can also point out that the highest level for lithium in this sample (121 ng/mL) was on Samos Island, and in our first post on lithium, we found hints that people on Samos Island are about as obese as Americans.  

Denmark is about 20% obese. In 2017, a team published this paper looking at lithium levels in 158 drinking water samples from 151 public waterworks supplying approximately 42% of the Danish population. Of these, 139 measurements came from “a drinking water sampling campaign, executed from April to June 2013, spatially covering the entire country”. They found an average level of lithium in their sample of 11.6 ng/mL (SD 6.8 ng/mL), with a range from 0.6 ng/mL in Western Denmark to 30.7 ng/mL in Eastern Denmark. This average is pretty high, though lower than the average in our American samples, but it’s also notable that the range and maximum levels are quite low. Even though the Greek and Danish averages are very similar, the Danish maximum value is about one-fourth the Greek maximum value. They also happily report the median value, 10.5 ng/mL.

Austria is about 20% obese. In 2018, a team published this paper looking at 6460 lithium measurements in drinking water samples from all 99 Austrian districts. The average level of lithium was 11.3 ng/mL (SD 27 ng/mL), with a range from “not detected” to 1300 ng/mL.The authors mention that the measurements are extremely skewed — between this and that extreme maximum value, we expect the median is much lower than 11.3 ng/mL.

Italy is about 20% obese. In 2015, a team published this paper looking at lithium concentrations in drinking water at 145 sites in Italy. The average level of lithium in the samples was 5.28 ng/mL, with a range from 0.110 to 60.8 ng/mL. The mean and the maximum level are markedly lower than the levels found in American water. 

Japan is about 4% obese, making it the leanest industrialized nation in the world. In 2020, a team published this paper (h/t commenter Patrick Halstead) looking at lithium levels in 434 drinking water samples in the 274 municipalities of Kyushu Island, the third largest island of Japan’s five main islands, which is home to about 10% of the population. They found that the average level of lithium in the samples was 4.2 ng/mL (SD 9.3 ng/mL), with a range of 0 ng/mL to 130 ng/mL. 

This average is lower than any of the other modern averages we’ve seen. If you look at the map below, you’ll see that only three municipalities had more than 40 ng/mL lithium in their water. Combined with the high maximum value of 130 ng/mL, this suggests an extreme skew, and suggests that the median value is lower than 4.2 ng/mL, maybe much lower. Unfortunately the authors haven’t publicly shared the raw data, so it’s hard to know what the median value really is.

There’s also this paper from 2020 (h/t commenter AJ), by some of the same authors, which looked at lithium levels in tap water samples across the 26 municipalities of Miyazaki Prefecture. Miyazaki Prefecture is part of Kyushu Island, so this is sort of zooming in on the result above. The average lithium levels in the tap water samples was 2.8 ng/mL, with a range from 0.2 ng/mL to 12.3 ng/mL. This time they also report the median, which is 1.7 ng/mL. Note that this median level is lower even than the median in the US in 1964.  

There’s also this paper from 2009, again by some of the same authors, again looking at a prefecture on Kyushu Island. This time they looked at Oita Prefecture, which borders Miyazaki Prefecture to the south. The only difference is that the data are somewhat older, being collected in 2006. Unfortunately they don’t seem to report a mean or a median, but the range was from 0.7 ng/mL to 59 ng/mL, and the authors note that “the distribution of lithium levels was considerably skewed.” Reporting on this paper, the BBC said, “The researchers speculated that while these levels were low, there may be a cumulative protective effect on the brain from years of drinking this tap water.”

Taken together, these three papers strongly suggest that Japanese people have much lower levels of lithium in their drinking water than Americans, or indeed any industrialized population.

We’re comparing a lot of unlike things here. We’re comparing means to medians; comparing sources from different countries and across different years; comparing samples from “groundwater”, “well water”, and “drinking water” without knowing if these are meaningfully different. But even with these limitations, we see that drinking water in America clearly has higher levels of lithium than the drinking water in other countries. This is apparent in the average levels found in large samples, but even more impressive is the differences in extreme values. Most other countries see maximum values of not much more than 100 ng/mL, while the American maximum value recorded was 1700 ng/mL, and a full 1% of samples in our best dataset contained more than 200 ng/mL lithium.

There’s more lithium in American well water than there is in the drinking water of these countries. But there’s also more lithium in the drinking water of these countries than there was in America in the 1960s. Greece, Denmark, Austria, and Italy all have more lithium in their water today than America did in 1964. The median in the dataset for America in 1964 was 2.0 ng/mL — we only have averages for most of these countries, but they all are much higher than 2.0 ng/mL. Denmark, where they do report the median, has a median value of 10.5 ng/mL. The only exception is Japan, where the median (if we could calculate it) might be around 2.0 ng/mL. But modern-day Japan is leaner than America was in 1964 — they’re about as lean as America was in 1890! 

Lithium and Depth

We can also look at the data from this new USGS report to see if there’s anything to our suspicion that drilling deeper and deeper wells is leading to more background lithium exposure. 

The most basic thing to look for is just to see if deeper wells have higher concentrations of lithium, and the answer is a clear “yes”. The paper itself comments, “Lithium concentrations … are positively correlated with well depth”, and naturally we see the same thing in the raw data.

The relationship varies slightly depending on how you do the analysis, but however you slice it, well depth and lithium levels are correlated at about r = 0.2. Because the sample size is several thousand, these are always statistically significant. The relationship also remains significant, and about the same strength, when we control for other variables we expect to be relevant.

In the case of the arsenic contamination in Bangladesh, arsenic was concentrated at a depth of around 50 meters. Wells at around this depth tended to be heavily contaminated, but wells that were either shallower or deeper were generally fine. We thought there might be a similar “sweet spot” for lithium, but so far we haven’t found much evidence for this. Overall there is a weak but pretty constant relationship, where the deeper the well is, the more lithium it contains. There are some indications of a sweet spot for certain types of aquifers, but we’d need to do a more detailed analysis.

There’s even some evidence that wells have been getting deeper over the years. This dataset doesn’t contain information about when wells were drilled, but when they were tested is a proxy for when they were drilled — a well tested in 2003 couldn’t have been drilled in 2008. When we look at the data, we see that the depth of the wells being tested shows a consistent increase over time. In the 1990s they tested 39 wells, and the deepest was only 260 feet deep. In the 2000s, they tested 1,288 wells, and 313 were deeper than 260 feet. Only two of the wells tested in the 2000s were more than 2,000 feet deep. In the 2010s and on, 33 of the wells they tested were more than 2,000 feet deep.

This is supported by the publicly-available well data we pulled from Vermont and Massachusetts earlier, where we see moderate correlations (about r = 0.3) between the year a well was completed and the overall depth. This is omitting the wells in the MA dataset that were listed as being 4,132,004 and 10,112,002 feet deep — we think these may be typos.

What about the maps? 

If there’s one thing we’ve learned from this project, it’s that people love maps. This paper contains a few, and they’re pretty interesting. This one is the most relevant: 

​​

One thing that you’ll notice is that the distribution of lithium in well water doesn’t match up all that well with the distribution of obesity. Colorado is the leanest state but has pretty high levels of lithium in its well water. Alabama is quite obese but levels of lithium in the well water there are relatively low. What gives? 

We think there are a couple of reasons not to be concerned about this. The first is that the sample is nowhere near representative. If you look at the map, you’ll see that the domestic-supply networks are thick around the coasts but thin in the interior of the country — except in Nebraska, where they are massively overrepresented for some reason. Only six wells were recorded in West Virginia and only three in Kentucky, which is too bad because those states seem pretty important. No effort seems to have been made to target population centers — this is a study by the USGS, so they are more interested in figuring out the features of major aquifers than of major cities. If a major city happens to be drawing from an especially contaminated source, they might have missed it.

The second is that there are big seasonal and weather effects, which they don’t adjust for. There’s almost no lithium in rain and snow — it’s essentially distilled water — so when it rains, lithium levels in groundwater drop as it becomes diluted with this influx of pure water. Similarly, there are seasonal effects — in part due to precipitation and snowmelt cycles — where lithium in the groundwater rises and falls over the course of the year.

But the third and most important thing is that all of these measurements are of well water, but many areas get their drinking water from surface sources rather than from wells. 

Let’s start with Colorado, since it’s the clearest example. As you can see from the map above, the average level of lithium in Colorado well water is higher than the national average. We have the raw data, so again we can tell you that the median level in Colorado wells is 17.8 ng/mL, the mean is 28.0 ng/mL, and the max is a rather high 217.0 ng/mL.

But this doesn’t matter, because almost none of the drinking water in Colorado comes from wells. Instead, most of the drinking water in Colorado comes from surface water, and most of that water comes directly from pure snowmelt.

Denver is the largest city in Colorado and also the capital. A company called Denver Water, which is Colorado’s oldest and largest water utility, serves the city of Denver and surrounding areas. They have this to say about where they get their water: 

Denver Water … relies on a system that collects rain and snow from across 4,000 square miles of mountains and foothills west of Denver. … On an average year, the utility captures 290,000 acre-feet of rain and snowmelt in its collection system. That’s roughly 94 billion gallons of water — or enough to fill up nearly 157 Empower Fields at Mile High. The water flows down rivers and streams, then through a network of tunnels, pipelines and canals to treatment facilities in the Front Range to be cleaned for delivery to homes and businesses. Because most of the water comes from mountain snowmelt in the spring, water is stored in mountain reservoirs until it is needed.

On another page, they say:

Denver Water is responsible for the collection, storage, quality control and distribution of drinking water to 1.5 million people, which is nearly one-fourth of all Coloradans. Almost all of its water comes from mountain snowmelt, and Denver is the first major user in line to use that water. Denver Water’s primary water sources are the South Platte River, Blue River, Williams Fork River and Fraser River watersheds, but it also uses water from the South Boulder Creek, Ralston Creek and Bear Creek watersheds.

Colorado Springs is the second-largest city in Colorado. Despite the name, they also get most of their drinking water from snowmelt. Per coloradosprings.gov: 

Colorado Springs is a community that lacks a natural water source. 80% of our community’s water comes via pipelines from the western slope, 200 miles away.

And per waterworld.com: 

Most of Colorado Springs’ current water comes from snowmelt, either on Pikes Peak or on the Western Slope. If snowfall is inadequate and precipitation falls as rain, the water is not easily captured in the high mountains where the Homestake pipeline begins. However, the Southern Delivery System (SDS) project would capture water as the flow emerged from the mountains as the Arkansas River and into Pueblo Reservoir.

Also enjoy this video from Colorado Springs Utilities called What it Takes to Drink Snowmelt.

Aurora is the third-largest city in Colorado (and right next to Denver). We bet you can guess where we’re going with this! From auroragov.org:

One of the benefits of living in a state that relies primarily on this surface water is that unlike groundwater, surface water is a renewable water source. 

Aurora receives 95 percent of our water from surface water sources, with the remaining five percent coming from deep aquifer groundwater wells. Replenished each year through snowmelt, Aurora’s water supply is transported from 180 miles away through a complex and extensive system.

As we mentioned above, precipitation has extremely low levels of lithium because it’s basically been distilled. In one study of rainwater in Montréal, they found a mean level of only 0.48 ng/mL. This means that if you are drinking rainwater or snowmelt, you are getting less lithium in your drinking water than any other group we’ve seen — less than in Italy, less than the Japanese, and less than Americans back in 1964. 

People in Colorado more or less are drinking nothing but snowmelt. It runs through rivers and reservoirs first, so it probably picks up some trace minerals and other contaminants from the slopes and riverbeds. But it doesn’t matter if the well water in Colorado is high in lithium — people aren’t drinking that, they’re drinking snowmelt.

Lithium aside, this is pretty interesting just from the perspective of Colorado being the leanest state. Snowmelt will be extremely low in pretty much every contaminant, so this seems to be additional evidence that obesity is caused by a contaminant that is carried in drinking water. We think you can still get exposure from other sources as well, probably your food — which is why Colorado is 20% obese, rather than 2% obese like premodern populations — but this seems like some evidence that drinking water alone makes some difference.

Other states also use surface water, but we’re pretty sure no one else is getting 95-100% of their drinking water directly from snowmelt. Utah is just on the other side of the ridge, but their Department of Environmental Quality says: 

Utah’s drinking water comes from either surface water (lakes, reservoirs, rivers) or ground water (wells or springs), altogether 1,850 sources. Utah’s larger cities generally use surface water and wells while its small towns depend on springs that serve the system all year long, supplemented by wells during the summer months.

Nearby Nebraska seems to get most of their drinking water from wells. According to one source, about 80 percent of the population consumes drinking water that is pumped from groundwater sources; according to another source, 85% of the population does. So unlike Colorado, Nebraska should be concerned about the levels of lithium in their groundwater — a median level of 17.6 ng/mL and a mean of 21.7 ng/mL — because they’re actually drinking it. And the rest of us should be concerned as well, because Nebraska is #3 in the nation for agricultural production.

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[Next Time: THE FATTEST CITIES]

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[PART I – MYSTERIES]
[PART II – CURRENT THEORIES OF OBESITY ARE INADEQUATE]
[PART III – ENVIRONMENTAL CONTAMINANTS]
[INTERLUDE A – CICO KILLER, QU’EST-CE QUE C’EST?]
[PART IV – CRITERIA]
[PART V – LIVESTOCK ANTIBIOTICS]
[INTERLUDE B – THE NUTRIENT SLUDGE DIET]
[PART VI – PFAS]
[PART VII – LITHIUM]
[INTERLUDE C – HIGHLIGHTS FROM THE REDDIT COMMENTS]
[INTERLUDE D – GLYPHOSATE (AKA THE ACTIVE INGREDIENT IN ROUNDUP)]
[INTERLUDE E – BAD SEEDS]
[PART VIII – PARADOXICAL REACTIONS]
[PART IX – ANOREXIA IN ANIMALS]
[INTERLUDE F – DEMOGRAPHICS]

Let’s talk about some of the new stuff we’ve learned about lithium.

Lithium Grease

Our first post on lithium mentioned lithium grease, which is used on all kinds of heavy machinery. We found this interesting because professions that work closely with cars, trucks, planes, and trains tend to be more obese than average, and if lithium causes weight gain, lithium grease might be able to explain this pattern.

We knew that lithium grease was a modern invention, but we recently found out that the timeline for lithium greases matches the timeline of the obesity epidemic even better than we realized — it was introduced in the 1940s, but only started seeing serious use in the 1980s. Here’s the story per The Society of Tribologists and Lubrication Engineers:

Greases made with simple lithium soap thickeners first appeared in the 1940s, starting with Clarence Earle’s 1942 patent (U.S. 2,274,675). Users found that these greases resisted water better than greases made with sodium soaps, and they performed better at high temperatures than calcium soap greases did. Lithium soap greases resist shearing, and they exhibit good pumpability properties, although they require the addition of antioxidants. This combination of advantages outweighed the extra manufacturing expense compared with calcium and sodium thickeners, and lithium soap greases (notably lithium 12-hydroxystearate formulations) quickly claimed a large share of the market (9). 

Lester McClennan patented the first lithium complex grease in 1947 (U.S. 2,417,428), but lithium complex greases did not become popular commercially until the early 1980s (9). For the past 20-30 years, manufacturers have been shifting away from thickeners based on simple lithium soaps to lithium complex thickeners because of the latter’s better performance at high temperatures, Waynick says. 

With this in mind, you can imagine our reaction when we saw an email drop into our inbox with the subject line, “Repeatedly eating lithium grease”. This email turned out to be from reader Emily Conn, sharing the following anecdote about a guy she used to work with: 

I used to work in HVAC repair with a guy named A—, and he was sort of famous in our company for eating lithium grease. The reason he did this was so that he could identify the sort of grease that had been used somewhere and then apply the same type. He could even taste differences between brands. We all touched the stuff, which I thought at the time was safe, but he was the only one who ever ate it.

Well, all the other health problems the guys in the company had, he had 10 times over. Not only was he extremely fat, he was also frequently out for medical issues, although I never knew what they were.

Another note for the story – I’ve never seen anyone else care about matching brands of lithium grease, not sure why A— thought it was important. Also, I never validated his claim that he could taste the difference between brands – that was what he said he could do but none of us ever checked.

This is just an anecdote and only a sample size of one, and may not be representative of all cases. Nevertheless, we strongly recommend that you avoid eating lithium grease.

What about the Middle East?

In our first post about lithium, we speculated that many Middle Eastern countries have high rates of obesity because they get a lot of their drinking water from desalination. Desalination removes all trace elements from seawater, but because distilled water is bad for pipes and trace elements are important for your health, the desalinated water is remineralized by blending it with some of the original sea water. 

Seawater has more than a bit of lithium in it, and lithium levels in the Persian Gulf are on the high end for seawater. Based on measurements of seawater in the gulf, we calculated that desalinated seawater in the Middle East could end up carrying a pretty big dose of lithium, somewhere in the range of 10-100 ng/mL.

(Also notable is that desalination produces lots of toxic brine, which is itself a problem.)

It’s true that 100 ng/mL is a pretty high level of lithium to find in your drinking water, but it’s not a total outlier — we see lithium levels this high or higher in places like Texas, some Greek Islands, and some parts of Austria. So 100 ng/mL is concerning, but it’s still surprising that Middle Eastern countries ended up so obese when there are other places that get similar doses.

Some Reddit comments recently introduced us to the Pima people of the Gila River Valley, who had very high levels of obesity way before the obesity epidemic started for the rest of the world, as high as 40% obese in 1970. In the course of looking into this, we learned that the Pima were exposed to very high levels of lithium in their food and water quite early on, because “in the Gila River Valley, deep petroleum exploration boreholes were drilled during the early 1900’s through the thick layers of gypsum and salty clay found throughout the valley. Although oil was not found, salt brines are now discharging to the land surface through improperly sealed abandoned boreholes, and the local water quality has been degraded.” Fun!

This led us to the literature on oil-field brines, which tend to contain huge amounts of lithium. How huge? Well first we need some comparisons. In drinking water, a low level of lithium is about 0.5 ng/mL, and high levels are 100 or 200 ng/mL. In some parts of Chile, however, drinking water can have up to 700 ng/mL, and in Argentina, up to 1000 ng/mL. In seawater, lithium concentrations are usually in the range of 100 to 1000 ng/mL. The highest concentrations of all are found in extreme locations like the Dead Sea, with 14,000 ng/mL of lithium, and 24,880 ng/mL in the headwaters of one river in Chile. 

All of these are dwarfed by the levels possible in oil-field brines. Here’s a quick review from a USGS paper released in May 2021:

Produced water from oil and gas wells can have extremely high concentrations of lithium (Dresel and Rose, 2010; Blondes et al., 2018). For example, waters from shale gas wells in the U.S. had reported lithium concentrations ranging from 10 to 634,000 [ng/mL] (median 25,000 [ng/mL]) and those from conventional oil and gas wells had concentrations ranging from <10 to 1,730,000 [ng/mL] (median 5000 [ng/mL]) (Blondes et al., 2018). Lithium and associated components of such brines may be accidentally or intentionally released to the surface or groundwater in certain locations (Tasker et al., 2018; McDevitt et al., 2019).

Another point of comparison is this report from 2019 on recovering lithium from “oil and gas produced water”. This includes a number of interesting observations, including that Smackover brines from the Smackover Formation, which extends from Texas to Florida, contain between 50,000 ng/mL and 572,000 ng/mL of lithium. This source is currently being considered for exploration by the Arkansas Smackover Lithium Project.

Some of these levels are very very extremely high indeed. The highest number we reported in our original post was 24,880 ng/mL in parts of Chile. In comparison, the MEDIAN concentration in waters from shale gas wells is 25,000 ng/mL. Many of these brines have lithium concentrations in the range of 100,000 ng/mL, and some contain more than 1,000,000 ng/mL!

The USGS report also mentions that lithium concentrations are higher in arid regions. All together, this seems pretty interesting because the Middle East is especially famous for 1) being very arid and 2) having lots and lots of oil wells.

In theory, these wells should all be sealed and/or the brines should be injected deep underground where they can never contaminate anything humans come into contact with. This is important because these brines are not only as salty as hell, but also radioactive. Fortunately, the oil and natural gas industry doesn’t make mistakes.

It seems quite clear that the Pima were exposed to lithium from brines leaking out of improperly sealed boreholes, so there is at least one example of accidental exposure. And the USGS report we quoted above acknowledges that “such brines may be accidentally or intentionally released to the surface or groundwater”. Is it possible that the Middle East is especially obese because of lithium leaking in from petroleum mining, rather than (or in addition to) lithium exposure from desalination? 

If this were true, one thing we might see would be especially high rates of obesity in oil field workers. There are some indications that this is the case. One paper looked at Kuwait Oil Company employees in 1999-2000, and found that 28.8% of field workers were obese, compared to only 25.1% of office workers. Still, both of these groups were less obese than Kuwait in general at the time (about 29% obese). There are also reports like this one, this one, and this one, that suggest that obesity is a particular issue for oil and gas workers, though the reports are frustratingly short on details.

We’ll also note that some of these reports focus on offshore oil workers in particular, and it seems that offshore oil rigs get much of their water from desalination (e.g. see here, here). 

“The mining industry,” says a paper from 2017 suggested by a reader, “has the highest proportion (76%) of overweight and obese employees in Australia.” This is in comparison to 62.8% of Australian adults in general. Tsai et al. (2008) looked at “4153 Shell Oil Company employees from three refineries, one each in Texas, Louisiana, California” in the years between 1994 and 2003. “For study subjects actively employed in 1994,” they report, “the most current examination data before 1994 were used. For employees hired after 1994, data were derived from the preemployment exams.” They found that 44.6% of employees were overweight, and an additional 29.0% were obese. For comparison, the general rate of obesity in the US was about 21% in 1994 and about 28% in 2003. (Though note that all these samples are majority male, often about 80% male, which increases the mean somewhat.)

It’s easy to see how this could be a problem in the Middle East, where there’s so much oil drilling. But is it a problem elsewhere? Is it a problem in the US? And could these brines really be getting into the average person’s groundwater?

The first thing to keep in mind is that the United States is one of the top three oil producing countries in the world, and as of this writing holds the #1 spot for most oil produced per day. We produce a lot of oil, and that means we also produce a lot of brine. 

The second thing to keep in mind is that we seem to be pretty bad at not spilling our brine everywhere. You’ll recall that the USGS report we quoted above said, “lithium and associated components of such brines may be accidentally or intentionally released to the surface or groundwater in certain locations.” This sounds bad enough, but the bird’s-eye view really obscures some of the horrible details. So let’s look at some sources for these horrible details. In no particular order: 

This report from North Dakota State University, which mentions that “the average well in North Dakota produces 18 barrels of brine per barrel of oil and three barrels of brine per barrel of gas,” and goes into some detail about “commonly used methods” for responding to brine spills. 

This report “characteriz[ing] the major and trace element chemistry and isotopic ratios … of surface waters (n = 29) in areas impacted by oil and gas wastewater spills in the Bakken region of North Dakota”, which is full of interesting tidbits. For example, we can see that there appear to be more leaks pretty much every year, and we can see that in this sample 46.7% of the brine leakage by volume came from pipeline leaks. We even have lithium measurements — we can see that in “Type A Spills” (whatever those are), the first sample contained 3,244 ng/mL lithium, the second sample contained 3,490 ng/mL, the third sample contained 478 ng/mL… you get the idea.

This report of an ACME Environmental response to an event where “500 barrels of produced water and 50 barrels of oil spilled into a drainage gully which directly flowed into a creek” in Central Oklahoma. The spill was vacuumed up and then the area was flushed with freshwater until “the salinity levels reached an acceptable level.”

This article from certifiedcropadviser.org, that tries to sound optimistic, but includes a number of concerning statistics. “North Dakota’s oil boom can have a salty side-effect,” it begins. “Wastewater from oil drilling and hydraulic fracturing – or fracking – is often laden with salts and can spill, contaminating soils. In 2014, for example, 42 such brine spills per week, on average, were recorded in North Dakota.” They discuss a new method for cleaning up such spills, but the method appears to remove less than half of the salts. “Other methods,” they tell us, “attempt to push the salts below the level plant roots can reach.”

This article from Rolling Stone, which documents some cases of brine trucks crashing and spilling thousands of gallons of brine into drinking water, discusses a case where a hauling company had been dumping brine into abandoned mine shafts for six years, and mentions that “brine has even been used in commercial products sold at hardware stores and is spread on local roads as a de-icer.” If they’re spreading it on the roads, that would uh, that would be a clear reason why it’s ended up everywhere:

Radioactive oil-and-gas waste is purposely spread on roadways around the country. The industry pawns off brine — offering it for free — on rural townships that use the salty solution as a winter de-icer and, in the summertime, as a dust tamper on unpaved roads. … In 2016 alone, 11 million gallons of oil-field brine were spread on roads in Pennsylvania … Much of the brine is spread for dust control in summer, when contractors pick up the waste directly at the wellhead, says Lawson, then head to Farmington to douse roads. On a single day in August 2017, 15,300 gallons of brine were reportedly spread.

This article from the Dallas Morning News, which documents some seriously concerning spills. Really this one is just worth quoting directly. Here are some choice excerpts: 

Five years ago, a broken pipe soaked the land with as much as 420,000 gallons of wastewater, a salty drilling byproduct that killed the shrubs and grass. It was among dozens of spills that have damaged the Johnsons’ grazing lands and made them worry about their groundwater.

…

An Associated Press analysis of data from leading oil- and gas-producing states found more than 180 million gallons of wastewater spilled from 2009 to 2014 in incidents involving ruptured pipes, overflowing storage tanks and even deliberate dumping. There were at least 21,651 individual spills. The numbers are incomplete because many releases go unreported.

Though oil spills get more attention, wastewater spills can be more damaging. Microbes in soil eventually degrade spilled oil. Not so with wastewater — also known as brine, produced water or saltwater. Unless thoroughly cleansed, salt-saturated land dries up. Trees die. Crops cannot take root.

“Oil spills may look bad, but we know how to clean them up,” said Kerry Sublette, a University of Tulsa environmental engineer. “Brine spills are much more difficult.”

…

The AP obtained data from Texas, North Dakota, California, Alaska, Colorado, New Mexico, Oklahoma, Wyoming, Kansas, Utah and Montana — states that account for more than 90 percent of U.S. onshore oil production. In 2009, there were 2,470 reported spills in the 11 states; by 2014, the total was 4,643. The amount spilled doubled from 21.1 million gallons in 2009 to 43 million in 2013.

…

The spills usually occur as oil and gas are channeled to metal tanks for separation from the wastewater, and the water is delivered to a disposal site — usually an injection well that pumps it back underground. Pipelines, tank trucks and pits are involved.

Equipment malfunctions or human error cause most spills, according to state reports reviewed by the AP. Though no full accounting of damage exists, the scope is sketched out in a sampling of incidents:

•In North Dakota, a spill of nearly 1 million gallons in 2006 caused a massive die-off of fish and plants in the Yellowstone River and a tributary. Cleanup costs approached $2 million. Two larger spills since then scoured vegetation along an almost 2-mile stretch.

•Wastewater from pits seeped beneath a 6,000-acre cotton and nut farm near Bakersfield, Calif., and contaminated groundwater. Oil giant Aera Energy was ordered in 2009 to pay $9 million to grower Fred Starrh, who had to remove 2,000 acres from production.

•Brine leaks exceeding 40 million gallons on the Fort Peck Indian Reservation in Montana polluted a river, private wells and the municipal water system in Poplar. “It was undrinkable,” said resident Donna Whitmer. “If you shook it up, it’d look all orange.” Under a 2012 settlement, oil companies agreed to monitor the town’s water supply and pay $320,000 for improvements, including new wells.

•In Fort Stockton in West Texas, officials in February accused Bugington Energy of illegally dumping 3 million gallons of wastewater in pastures. The Middle Pecos Groundwater Conservation District levied a $130,000 fine, alleging a threat to groundwater, but the company hasn’t paid, contending the district overstepped its authority.

•A pipeline joint failure caused flooding on Don Stoker’s ranch near Snyder in West Texas in November 2012, turning his hackberry shade trees into skeletons. Vacuum trucks sucked up some saltwater and the oil company paid damages, but Stoker said his operation was in turmoil. “I had to stay out there three days and watch them while they were getting the saltwater out, to make sure they didn’t totally destroy the whole area.”

So yeah, maybe these brines are sometimes ending up in the groundwater.

No one is drinking these brines directly. For one thing, doing so would almost certainly kill you. But the lithium concentrations in these brines are so high that even a small amount leaching into your drinking water could have big consequences. 

Let’s imagine that a groundwater source containing no lithium mixes with a brine that contains 100,000 ng/mL lithium. If the brine mixes at 1%, the water source ends up containing 1,000 ng/mL lithium, higher than pretty much any lithium levels we’ve seen in drinking water. If the brine mixes at 0.1%, the water source still ends up containing about 100 ng/mL lithium, which is pretty high. But we see about 100 ng/mL in the data for the Pima (coming up below), and that’s probably from a leak from an old well, so 100 ng/mL looks pretty plausible for a brine leak. Even if it were only mixing at 0.05%, that would still be 50 ng/mL in your drinking water, which is quite a bit.

Return to Gila River Valley

A while ago, we looked at the case of the Pima people of the Gila River Valley. During our investigation, we became interested in a paper by Sievers & Cannon (1973). Sources suggested that this paper contained a lot of detail about lithium contamination in the Gila River Valley in the early ‘70s, but we weren’t able to track it down.

But in recent developments, commenter Ralph Waldo Porcupine found the original paper and sent us a copy. Thanks Ralph!

This paper is short, but contains a number of interesting details, so let’s jump right in. To begin with, the obvious pull quote is:

It is tempting to postulate that the lithium intake of Pimas may relate 1) to apparent tranquility and rarity of duodenal ulcer and 2) to relative physical inactivity and high rates of obesity and diabetes mellitus.

Native Americans have higher rates of obesity and diabetes than Caucasians, so we should expect relatively high rates among the Pima either way. However, the paper makes it clear that the rates of both diseases among the Pima are “extraordinary”, even for Native American populations at the time, “the highest ever reported”. For full context:

Most southwestern tribes greatly exceed whites in prevalence of diabetes mellitus. Observations at the PIMC reveal that the Pima tribe has the highest diabetic rate—45% of adults (12). Population studies by Bennett confirm an extraordinary frequency of diabetes mellitus in Pima Indians—the highest ever reported and 10 to 15 times that for the general population (2).

…

Most American Indian tribes have a very high prevalence of obesity. … The Pima tribe has an especially high rate of marked obesity.

The obvious question is, how much lithium was in their water back in the 1970s? The paper doesn’t name a specific number, but judging from Figure 1, the median lithium level in their drinking water was around 100 ng/mL. You’ll recall that this is pretty high even compared to the modern water sources we reviewed in our first post on lithium.

This figure is a little hard to read, so let’s orient you. Each “chemical constituent” is a vertical bar showing the range of concentrations in 77 samples, and a small triangle indicates the median value. We can see that the triangle for lithium is hovering around 10^-1 ppm, which works out to 100 ng/mL.

The diagonal line cutting through the figure indicates the median for each constituent in municipal waters, and the horizontal location of each of the bars tells you how much of each constituent is normally in “municipal waters”. This may actually be the most important aspect of the figure, because it answers a longstanding question: back in the day, how much lithium was in the average water supply? We know that in the early 1970s the Pima were getting about 100 ng/mL, but how much was everyone else getting? 

Figure 1 suggests that back in the early 1970s, the average concentration of lithium in “municipal waters” was just slightly more than 1 ng/mL. This seems like a pretty big deal — the Pima were not just being exposed to a pretty high dose in their water, their dose was 50-100x higher than the median dose in American municipal water sources at the time! 

But we can actually do one better, because Sievers & Cannon cite their source for this diagonal line, a 1964 paper called Public water supplies of the 100 largest cities in the United States by Durfor & Becker. This whole paper is available on Google Books where you can also download a copy for yourself as a PDF.

Just like the title says, this paper looks at the public water supplies of the 100 largest cities in the United States in 1964, and looks at what was in their water. Unlike most modern sources, lithium was on their list — so amazingly, we have pretty good records of how much lithium was in American drinking water all the way back in 1964. 

The records are quite clear. The median level of lithium in their samples was only 2.0 ng/mL, 50 times less than the median for the Pima and quite low compared to modern sources.

The minimum level detected was “not detected at all”, and perusing the numbers from individual cities, this makes a lot of sense. As you flip through the 100 cities, you see that lithium levels are generally quite low — often around 1 ng/mL, but sometimes no lithium at all. 

Occasionally lithium levels are higher, especially for cities in arid locations like Arizona and Texas. The maximum level detected was 170 ng/mL (in Texas), which is a lot — but this makes sense given what we see with the Pima. We already knew that some water supplies were contaminated with lithium that far back, and it’s no surprise that these water supplies are in Arizona and Texas! In fact, while it’s hard to read from Figure 1, it looks like the maximum value recorded in the Gila River Valley was more than 170 ng/mL, probably closer to 250 ng/mL. But notably, not all water supplies from arid locations had high concentrations of lithium, not even in Texas.

This also matches the other historical sources we’ve been able to find, though most of them have a much more limited scope. 

Municipal Drinking Water and Cardiovascular Death Rates from 1966 looked at water from 88 cities. They don’t give much detail, but suggest that the lithium levels in city drinking water were somewhere in the range of 16.8 ng/mL to 5.3 ng/mL. This may seem maddeningly vague to you — it also seems vague to us, so we’re more inclined to trust the 100-cities paper from above, since it is much clearer and provides more detail.

This paper from 1970 looks at lithium levels in the drinking water of 27 Texas communities in summer and fall 1968. They found that lithium was present in measurable amounts in the drinking water of 22 of the 27 communities, and found levels above 11 ng/mL in 15 of the 27. Matching what we saw in the 100-cities paper, some sources were found to contain as much as 160 ng/mL. Texas wasn’t universally contaminated back then, but like Arizona, it had some extreme cases.

Mood and Lithium in Drinking Water from 1976 looked at 384 drinking water samples from Washington County, Maryland. They found that 37.5% of the samples had lithium levels below 1.9 ng/mL and 75.2% had lithium levels below 5.9 ng/mL. About 90% of samples contained less than 10 ng/mL, and the highest recorded level was a mere 32 ng/mL.

Wolfberries

Sievers & Cannon also found that trace elements in the groundwater accumulate in some plants but not in others. Lithium in particular seems to concentrate in specific plants to an incredible degree:

Vegetation is low in most trace elements but some food plants concentrate particular ones. Mesquite beans accumulate strontium; cabbage accumulates sulfate; beans concentrate molybdenum and wolfberry contains an extraordinary 1120 ppm lithium in the dry weight.

…

Figure 2 shows the chemical content of produce and plants that grow on the sandy alluvium of the Gila River. This vegetation has low concentrations of most trace metals but has high levels of lithium. The median level of lithium for Pima Reservation plants is 1.4 ppm (general average elsewhere, 1.0 ppm) but the mean is much higher due to abnormal accumulation by the wolfberry (or squawberry; Lycium californium).

High concentrations of particular elements in certain vegetations become important to human health if the plants are consumed in quantity. Some unusual accumulations in edible plants are shown in Table I. The wolfberry, with an extraordinary lithium content of 1120 ppm, is used occasionally for jelly. 

They’re not kidding when they say “extraordinary” — 1,120 ppm is equivalent to 1,120,000 ng/mL! 

Let’s unpack this a little. Elsewhere in the paper they say, “Pima Indians drink about 1.6 liters per day (9) of hard water.” Since the level of lithium in the water seems to have been around 100 ng/mL, which is the same as 100 µg/L, this suggests that they got about 160 µg of lithium per day from their drinking water.

In comparison, they say that the wolfberry is “occasionally” used for jelly. Let’s say that this means an average of one tablespoon of wolfberry jelly per day, and let’s assume that the dose is the same in the jelly as it is in the wolfberry itself. A tablespoon is about 14 milliliters, so with a lithium concentration of 1,120,000 ng/mL, they would be getting 15,680,000 ng or 15,680 µg of lithium from the jelly. If these numbers are anywhere near correct, then the Pima were getting around 100 times more lithium from wolfberry jelly than directly from their drinking water. 

This might help us square the fact that lithium seems to be associated with weight gain, but the trace amounts in water are so much smaller than the therapeutic doses given by psychiatrists. By the calculations we did in our first post on lithium, the “minimum efficacious” therapeutic dose is about 600,000 µg per day, which would take about 40 tablespoons of wolfberry jelly (2 ½ cups, or slightly more than one jar of jelly). Alternatively, 3,750 liters of Gila River Valley water. It would be hard to drink that much water, but you could definitely get a therapeutic dose if you ate enough jelly. We don’t know what dose of lithium you need before the weight gain starts kicking in, but whatever it is, you can get there a lot faster if lithium is concentrating in the plants you eat.

Let’s imagine that corn accumulates lithium similarly to the wolfberry. (Just to be clear, this is purely a hypothetical — we have no reason to suspect corn in particular.) If your corn is irrigated with pure water containing no lithium, then the corn also contains no lithium. But if the corn is irrigated with water containing 100 ng/mL lithium, like the water in the Gila River Valley, then the corn accumulates a lot of lithium, maybe as much as 1,120 ppm / 1,120,000 ng/mL like the wolfberry does. Certain corn products might contain even more, if they concentrate the lithium further. If the corn is irrigated with water somewhere in between those two doses, then the corn ends up containing some lithium, but probably not as much.

This is complicated even further by the fact that (again just picking on corn as an example, this is true of most crops) there are many different varieties of corn. We treat them all as simply “corn”, but there can be important differences between different varieties, and some varieties might end up concentrating more lithium than others. This means that it’s impossible or sort of even meaningless to ask a question like, “how much lithium is in corn?” Well, what kind of corn? Where is it from? How much lithium was the irrigation water when it was being grown? 

So in the future, we need to keep an eye out for plants that might be concentrating lithium. Even if they are only exposed to trace amounts in their water, they could end up concentrating levels around 10,000 times higher! We grow a lot of crops — corn, soybeans, wheat, grapes, rice, almonds, peanuts, apples, etc. — which of these concentrate lithium from their water? Which are commonly exposed? 

This complicates things somewhat, but the good news is that if this is the case, we wouldn’t have to worry too much about lithium in our actual drinking water. Instead, we would want to make sure that the water we use to irrigate crops is as low in lithium as possible, which seems much more manageable.

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[Next Time: WELL WELL WELL]

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[PART I – MYSTERIES]
[PART II – CURRENT THEORIES OF OBESITY ARE INADEQUATE]
[PART III – ENVIRONMENTAL CONTAMINANTS]
[INTERLUDE A – CICO KILLER, QU’EST-CE QUE C’EST?]
[PART IV – CRITERIA]
[PART V – LIVESTOCK ANTIBIOTICS]
[INTERLUDE B – THE NUTRIENT SLUDGE DIET]
[PART VI – PFAS]
[PART VII – LITHIUM]
[INTERLUDE C – HIGHLIGHTS FROM THE REDDIT COMMENTS]
[INTERLUDE D – GLYPHOSATE (AKA THE ACTIVE INGREDIENT IN ROUNDUP)]

People have been asking us if we’re going to review the literature on seed oils. 

We weren’t aware this was such a popular theory when we wrote the series, so we didn’t think to address it. Briefly, this theory says that some of our food oils — usually soybean, corn, canola, cottonseed, and safflower oils, but sometimes others — are behind the modern meteoric rise in obesity rates. Clearly this is relevant to our interests. 

People are split over exactly what to call the culprit — seed oils, industrial seed oils, vegetable oil, etc. These terms may mean slightly different things to different people, but ultimately these are all a closely related set of theories. In this post, we will go with the term “seed oils” because it is the shortest. 

Here is just a small subset of the sources people sent us:

• How Industrial Seed Oils Are Making Us Sick by Chris Kresser
• Death by Vegetable Oil: What the Studies Say by Jeff Nobbs
• The Case Against Processed Vegetable Oils by The Organic Consumers Association
• The SCD1 Theory Of Obesity Archives / The Croissant Diet Archives from Fire in a Bottle

We haven’t read everything ever written on seed oils because there are a truly enormous number of pieces on this idea. But we do think it’s worthwhile to do our own review of the theory, so here goes. 

Plausibility

There are a number of things that make this hypothesis attractive. For one, these oils truly are in everything. 

One of the authors of this blog went on a couple dates with a girl who had a serious corn allergy. Unfortunately for her, corn oils and other corn byproducts are all over the damn place. She couldn’t eat out at restaurants or buy most prepared foods. She couldn’t have chocolate. She couldn’t even eat citrus, because corn proteins are a component in the pesticides/preservatives sprayed on citrus trees and fruit. She could eat apples if she peeled them, but even that was a risk. She mostly lived on rice, rice noodles, a small number of safe vegetables, and potatoes (which, to be fair, are the prince of food). 

And this is just corn! We’re looking for a factor that is omnipresent in the environment and difficult to escape regardless of one’s diet, and seed oils do seem to fit the bill.

We should also note that the contaminants theory more or less predicts something like seed oils. Any contaminant that causes obesity probably bioaccumulates in plants and animals. If it bioaccumulates in plants, then highly concentrated byproducts of those plants might contain higher concentrations of the contaminant. This would vary based on the species of plant (some will bioaccumulate more than others) but we would expect to see especially high levels of contaminants in some extremely concentrated food products. 

Seed oils are also highly processed (check out the cool/disturbing video at that link) so they have many opportunities to come into contact with industrial contaminants. “I thought it was going well,” says YouTube commenter Sam De Francesco, “up to the bit about using a chemical solvent to remove the remaining oil from the canola cake. It went downhill from there quickly.”

The two theories are complementary, and it’s possible that both could be true. We can even look at specific contaminants to see if there might be a connection.

There is some work on measuring the levels of PFAS in cooking oils, and they do record some PFAS being detected in “Edible Oil Samples from Markets in Beijing, China, in 2013”, including corn oil, soybean oil, etc. But these levels of contamination are in about the same range as PFAS found in other foods, like milk, not thousands of times higher.

We can’t find any actual measurements of lithium levels in different food oils. This paper finds no relationship between vegetable oil consumption and lithium in the blood plasma of 922 Germans, but the food consumption measure was all self-reported, and people are probably not fully aware of how much vegetable oil is in many foods. Some secondary sources (here, here) say that lithium is most concentrated in vegetables, cereals, and grains, which would sort of line up with the seed oil hypothesis, but we can’t find the primary sources for these claims, so take this one with a grain of salt for sure. 

Glyphosate’s Hail Mary

In a previous post, we took a look at glyphosate and concluded that it doesn’t seem like glyphosate could be a primary driver of obesity, and probably doesn’t contribute to obesity at all. There is one longshot hypothesis, however, of how glyphosate might play a role in the obesity epidemic, or at least the increase we’ve seen since the 1990s. 

When reviewing the list of Roundup Ready crops, varieties designed to be sprayed with huge doses of glyphosate, we couldn’t help but notice that soybeans, corn, canola, and cotton are all on the list (though not safflower). As a result, these crops are sprayed with much more glyphosate than normal. This seems like kind of a weird coincidence. You’ll also recall that in 2016, the EPA found glyphosate in 63.1% of corn samples and 67.0% of soybean samples they tested. 

The level of contamination was quite low in all of these samples, but seed oils are highly concentrated, so the levels of contamination in corn oil could potentially be hundreds of times higher. That said, we haven’t been able to find any data on glyphosate levels in any of these oils, so it’s hard to tell. There’s some evidence that glyphosate is in more foods than officially recognized (thanks to commenter Louis for finding this one!), but that’s not a direct connection to seed oils per se. We also found one claim that glyphosate “does not mix with oil, so there are negligible glyphosate residues in vegetable oil from treated crops such as soybeans, canola and corn”, but this is from gmoanswers.com.

Challenges

The seed oil account of obesity also has several weaknesses, which make the hypothesis seem less likely.

First of all, it seems unlikely that there is a problem with the sources of the oils themselves. Soybeans and corn have been eaten for centuries without a wave of obesity. Rapeseed (you know this as the source of canola oil) is yet another Brassica, which people have been eating forever. 

It could all be in the dose, though. These seed oils are highly concentrated — hundreds or thousands of servings of the relevant vegetable are needed to make one serving of the oil — so if there is some corn enzyme that is harmless at a small dose but dangerous when the dose is 100x higher, that could lead to corn being harmless but corn oil being an issue. A common saying among seed oil proponents is “the dose makes the poison,” and that certainly might be the case.

We notice that the seed oils under suspicion were developed around 1900-1930, which seems a little too early to match the timeline for obesity. People have been eating more and more of them over time, but this trend took off around 1940 and doesn’t show a clear inflection point around 1980. This isn’t damning evidence, but it doesn’t quite fit the pattern. 

In addition, seed oils face the same problems faced by every food-based explanation for the obesity epidemic.

Seed oils have a hard time accounting for patterns like obesity being related to altitude, and wild animals also becoming obese. Maybe wild animals are eating scraps of human food out of dumpsters behind the 7-11, but it’s not clear why people at low altitudes would be eating more seed oils than people at high altitudes.

Seed oils also seem unable to account for the big differences between obesity rates in different professions. It doesn’t seem like people in different professions are likely to eat different amounts of seed oils, but they do seem likely to be exposed to different contaminants at work.

Similarly, there is a large amount of variance in obesity rates between countries, and there has been for a long time. Why is the Middle East so obese? Why has Kuwait always been one of the most obese countries in the world? Why was Kuwait 20% obese in 1979, back when the obesity rate for the US was only 13%? It doesn’t seem like seed oils could be behind the high rates of obesity in the Middle East, which limits the possible role they could play in driving the obesity epidemic.

Health Claims

Of course, what we’re really interested in is whether or not seed oils are related to weight gain and obesity.

It’s unfair to look through a literature and start with some random papers. You want to let the theory’s supporters point you to the evidence they feel is strongest, the evidence they think is most important. We wanted to look at the strongest possible argument, the sort of case that only a supporter could put together. So we decided to start by looking at one person’s case against seed oils.

For this purpose, we decided to focus on work by Jeff Nobbs, because his series was the best of the many arguments we saw, and we want to engage with the strongest version of the theory. Nobbs cites lots of primary sources, links directly to them, and tells you which parts of the findings he thinks are relevant. He doesn’t hit you in the face with a bunch of biochem claims right out of the gate. He doesn’t engage in name-calling and doesn’t try to scare the reader by going on about how dirty or unnatural seed oils are, something we can’t say about some of the other sources we saw. He just shares the evidence that convinced him and explains why he thinks it’s important.

In Part 1 of his series, Nobbs does a really great job describing how levels of chronic disease and obesity are increasing, and reviewing the evidence for just how weird this is. He hits a number of the same points we made in our review of the mysteries surrounding obesity, and often he makes a more compelling case for their weirdness than we did. In particular, he does a better job describing how exercise rates are increasing. We especially like this figure: 

Part 2, called Death by Vegetable Oil: What the Studies Say, reviews a number of studies that suggest that seed oils (Nobbs prefers the term vegetable oil, but it’s essentially the same thing) contribute to health conditions like cancer, dementia, and weight gain. In this series we are primarily interested in obesity, so we will stick to the weight gain results.

In this post, Nobbs references four studies showing an obesity-seed oil connection:

In one study, rats were divided into different groups receiving diets identical in fat, protein, and carbohydrate calories but differing in the source of the fats. The rats in the group receiving fat from safflower oil had a 12.3% increase in total body weight compared to the rats eating traditional fats [6].

In a randomized trial on rabbits, three groups of rabbits were given access to identical foods, with only one difference: the first group of rabbits was fed unheated vegetable oil, the second group was fed vegetable oil that had been heated once, and the third group was fed vegetable oil that had been repeatedly heated multiple times. Everything else about their diets was kept the same [7].

The outcome? Compared to the group of rabbits eating unheated oil, the group eating single heated oil gained 6% more weight, and the group eating repeatedly heated oil gained 45% more weight!

A 2020 study in mice showed that consumption of soybean oil leads not only to weight gain, but also to gene dysregulation that could cause higher rates of neurological conditions like autism, Alzheimer’s disease, anxiety, and depression [8].

In another mouse study, feeding mice the equivalent of 2 tablespoons of canola oil per day is associated with worsened memory, learning ability and weight gain, along with “considerable neuronal damage” and increased formation of beta-amyloid plaques, the signature of Alzheimer’s disease [10].

Links 8 and 10 are to news sites, not to the original research papers, but as far as we can tell, 8 is probably this paper and 10 appears to be this paper.

We do want to mention at this point that all of these studies were conducted on animals, not humans. (Nobbs also knows this, of course.) We recognize the value of animal studies and we often cite them ourselves, but it’s curious that there seem to be no studies showing that seed oils cause weight gain in humans — more on this in a bit.

These sources describe what Nobbs says they do, showing connections between seed oil consumption and weight gain. And in fact there are many other studies that also show this connection — this study shows soybean oil led to more weight gain than other oils (in mice), this study shows soybean oil led to more weight gain than fish oil and palm oil (in rats), and this study shows safflower oil led to higher levels of leptin (but not body weight) compared to animal-based fats (also in rats).

However, there are also studies that show essentially no difference between seed oils and other oils in terms of weight gain. For example, in this study soybean oil led to an equal amount of weight gain as lard and palm oil, and canola oil led to less weight gain than the other three (still in rats), and in this study lard, sunflower oil, and palm olein oil led to nearly identical weights (mercifully, in vervets this time). 

Many other studies find the exact opposite, that seed oils cause less weight gain than other fats, including animal fats. For example, this paper found that a butter-rich diet led to more weight gain than a canola-rich diet (in rats), this paper found that a lard diet led to greater weight gain than safflower oil (in mice), and mice that were started on a lard diet and then switched to safflower oil actually started losing weight, this paper reviewed the literature and found that pretty much any high fat diet leads to some weight gain (in rats and mice), and the paper Body Fat Accumulation Is Greater in Rats Fed a Beef Tallow Diet than in Rats Fed a Safflower or Soybean Oil Diet found what it says on the tin. 

Even this is only a small selection of the large number of papers on this topic. Some of these papers are probably better than others — some we should take seriously, and others we should discount. Probably a bunch of these studies are crap. If someone wants to do a deep dive into these papers, and all the other ones out there, to try to figure out the state of the literature, we would be interested in reading that piece. But even if someone did a deep dive, we doubt there would be a clear result. It’s hard to look at this literature and say anything more than “wow that looks complicated”.

This is just one of those very large literatures where you have to be careful about drawing a conclusion from only a few studies. “Some studies where seed oils lead to more weight gain than other fats, some studies where they lead to less, and a couple studies where there’s no difference” is what we should expect to see if there is a small effect in either direction, or no effect at all.

There certainly doesn’t seem to be a strong effect here. If the effect were strong, it would be detected more reliably. So if seed oils have an effect on weight gain (in mice, rats, and vervets), it’s a weak effect at most, and it’s not clear from the evidence whether seed oil causes more or less weight than other fats.

Another problem with the weight gain results in rodents and monkeys is, why do none of the human studies find the same thing? Nobbs cites a number of studies on people, but none of the ones we looked into show any evidence that seed oils cause weight gain in humans. 

Let’s take a look. The Los Angeles Veterans Administration Study specifically mentions, “the unrestricted consumption of the two diets had no significant effect on average body-weight.” The Minnesota Coronary Experiment reports BMI in both conditions and finds them to be nearly identical, 24.6 versus 24.5. 

The MARGARIN Study reports BMI for all conditions and finds no difference in people who ate diets with margarine made with more fat from vegetable oil versus margarine made with less fat from vegetable oil. 

The Sydney Diet-Heart Study had two groups start out with similar BMIs (25.4 vs. 25.1) and BMI in both groups went down by a similar, small amount (ending up at 24.5 vs 24.3) after 12 months, regardless of whether they were eating mostly safflower oil and margarine, or mostly olive oil and butter.

These studies generally run for several years and have much higher sample sizes than the studies run on animals, and of course they’re looking at humans. If there’s no evidence in these studies that people gain weight when eating seed oils, then any effect of seed oils on weight would have to be very small or very subtle. Or, there might be no effect at all.

In fact, this is pretty strong evidence against seed oils causing obesity. If seed oils cause weight gain when people eat them, why didn’t seed oils cause weight gain when people ate them? Sure we didn’t review every study out there, but these are four rather large studies (a couple hundred to a couple thousand people each) and all of them show an effect of seed oil on weight that is absolutely zilch, bupkis, nothing. This is more than “no smoking gun”, this is “suspect was in another country giving a speech in front of 10,000 people on live TV.”

Rigor

And also… ok, we do want to pick on the rigor here, just a little.

Nobbs says, “In the Los Angeles Veterans Administration Study, the group of participants who increased fat from vegetable oil–while keeping total fat the same–were 82% more likely to die from cancer compared to the control group that didn’t increase fat from vegetable oil.” 

This sounds very impressive — but as far as we can tell, it is referring to this result: “31 of 174 deaths in the experimental group were due to cancer, as opposed to 17 of 178 deaths in the control group.” This is about 82% more in the experimental group, but as you can see, the absolute numbers are quite small. 

This difference is not even statistically significant, which the authors note, giving p = .06. In addition, they begin the discussion by noting, “The experience of other investigators using similar diets has not been the same.” They mention a couple other studies, including one from London which tested a diet high in “soya-bean oil”, where there were 6 cancer deaths in the control group and only one cancer death in the group eating a diet high in “soya-bean oil”.

We see something similar in the other studies. Nobbs mentions that “the group consuming more vegetable oil had a 62% higher rate of death during the seven-year study compared to the group eating less vegetable oil” in the Sydney Diet-Heart Study. Again, this sounds like a lot. We’re not entirely certain which result he’s referring to, but as far as we can tell this is also not significant, p = .051. In fact, every p-value reported in this paper seems to be between .02 and .13, which does not inspire confidence and is probably an indicator of p-hacking. Either way, the majority of these results are not statistically significant, and if we were to apply a simple correction for multiple comparisons, none of them would be.

In the MARGARIN Study, the “seven times higher” figure refers to one death in the less-vegetable-oil group and seven deaths in the more-vegetable-oil group. The authors note that this is “not significant because of the small numbers.” They don’t report a p-value here, so we double-checked their analysis just to be sure and found the same thing, p = .096.

The evidence in the Minnesota Coronary Experiment is a little more mixed, but the authors themselves do not seem to have access to the raw data, and in reference to the apparent increased mortality in adults over 65, say, “in the absence of the raw data, however, we cannot determine the statistical significance of this finding.”

Nobbs did a good job reviewing the literature and providing direct references to the studies he draws his conclusions from. But the literature on weight gain in animals is far larger and more mixed than many people realize, and doesn’t clearly point to seed oils causing obesity. The literature on seed oil consumption in humans consistently shows that seed oils cause no more weight gain than other fats. When we took a closer look at some of these studies, we found serious problems with several of the analyses. The evidence here is weak at best. 

This doesn’t mean that seed oils, or vegetable oils, or whatever you want to call them, are good for you. They may still be very bad for you, and the case for other health effects (including a connection with cancer) seems stronger. But it doesn’t look like they could be a major cause of the obesity epidemic, and probably, they play no role at all.

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[Next Time: PARADOXICAL REACTIONS]

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[PART I – MYSTERIES]
[PART II – CURRENT THEORIES OF OBESITY ARE INADEQUATE]
[PART III – ENVIRONMENTAL CONTAMINANTS]
[INTERLUDE A – CICO KILLER, QU’EST-CE QUE C’EST?]
[PART IV – CRITERIA]
[PART V – LIVESTOCK ANTIBIOTICS]
[INTERLUDE B – THE NUTRIENT SLUDGE DIET]
[PART VI – PFAS]
[PART VII – LITHIUM]
[INTERLUDE C – HIGHLIGHTS FROM THE REDDIT COMMENTS]

Glyphosate is a herbicide and all-around general weed killer that you probably know as the active ingredient in Roundup *whip cracks*

We were put onto the trail of this here varmint by Justin Mares, who pointed out that there are several reasons to be suspicious of glyphosate. We’ll start with the fact that this stuff is pretty much everywhere. “Because of its widespread use, glyphosate is in water, food and dust, so it’s likely almost everyone has been exposed,” says PBS.

Most sources say that glyphosate has a relatively short half-life in both soil and water, though apparently this “can vary widely based on environmental factors” and “values between 2 and 197 days have been reported in the literature.” Many sources downplay this contamination, emphasizing how quickly it degrades, but it does seem to end up in groundwater, as there is a whole water treatment literature about how to remove it (see also this other review paper). 

Relevant to our interpretation of the altitude mystery, one study that examined glyphosate contamination in two rivers in Mexico found that the rivers were generally (though not always) more and more contaminated as they flowed downstream.

Glyphosate was patented in 1971 and first sold in 1974, but the FDA didn’t test for glyphosate in food until 2016, which seems pretty weird. The results of these tests are publicly available — in the report from 2016, we see that they tested 274 samples of corn, 267 samples of soybeans, 113 samples of milk, and 106 samples of egg for glyphosate. No glyphosate at all was detected in the milk or eggs, but 63.1% of corn samples and 67.0% of soybean samples showed some glyphosate contamination, though none contained glyphosate levels above the limit set by the EPA. It’s clearly in some foods, though apparently less in animal products and not at especially high levels overall.

Glyphosate can affect the growth of microorganisms that rely on a specific pathway for growth, but this paper finds that most gut bacteria don’t have that pathway, and so glyphosate probably doesn’t affect their growth. On the other hand, this paper says that “54% of species in the core human gut microbiome are sensitive to glyphosate.”

There’s also some evidence that glyphosate interferes with various enzymes, at least in rats. Some of these enzymes are related to the metabolism and clearance of many drugs, and interference with these enzymes does seem to sometimes lead to negative drug interactions. This suggests that even if glyphosate doesn’t cause obesity by itself, it could potentially make people more susceptible to other compounds that do.

In addition there is at least one speculative paper arguing explicitly that glyphosate’s suppression of cytochrome P450 enzymes leads to many modern diseases, including obesity. However, we should mention that the journal that published this paper found it so weird that they added a note about “potential bias in opinions and bias in the choice of citation sources used in this article” and issued “an Expression of Concern [emphasis in the original] to make readers aware that the approach to collating literature citations for this article was likely not systematic.” Also see this pushback, and this pushback from a group funded by the American Chemistry Council, American Petroleum Institute, etc. etc.

When we look at a map, the distribution of glyphosate use in the United States matches county-level obesity data pretty darn well: 

It’s not a perfect match, but it’s pretty striking. Granted, this also looks a lot like the distribution of other pesticides, for example our old friend 2,4-D:

And Atrazine, another common pesticide:

Maps of pesticide use mostly highlight agricultural regions, regardless of the pesticide you look at. The big difference is that unlike these other pesticides, glyphosate is used more and more every year, matching the rise in obesity. Again from the USGS:

Glyphosate (interestingly, the increase seems to have stalled around 2012?):

2,4-D:

Atrazine: 

Glyphosate was developed to fight weeds in the early 1970s and was first brought to market in 1974 as Roundup. Since then, glyphosate use has increased pretty much every year, both in the US and worldwide.

This is actually a little on the late side, especially since glyphosate saw relatively limited use before the 1990s. Things really kicked in with the introduction of genetically engineered Roundup Ready crops. Roundup kills most plants, so it kills most crops too, and in the beginning the only way to use it was to spray selectively. But in 1996 Monsanto introduced Roundup Ready soybeans, which are resistant to glyphosate. Now farmers could dump Roundup on the whole field and kill everything but the soybeans. This was followed by Roundup Ready corn, canola, sugar beets, cotton, and alfalfa. These new resistant varieties led to a huge increase in glyphosate use during the 1990s and onward.

(In addition, we should note that Kuwait was already 18% obese by 1975, and it’s hard to see how glyphosate could be responsible for that.)

Round Down

There’s some circumstantial evidence that if contaminants are responsible for obesity, at least one of those contaminants is related to agriculture. As we see from the maps above, the most obese parts of America are largely farm country. If we were to suspect an agricultural chemical, glyphosate would be at the top of our list.

But there are many more signs that the main contaminants are not agricultural. If the most widely used herbicide in the United States were the cause of obesity, then we would expect agricultural workers to be especially obese, as a result of their high level of exposure. Instead, we see that the rate of obesity among agricultural workers is pretty average — sometimes slightly higher than average, sometimes slightly lower.

Agricultural workers are clearly exposed to glyphosate. One study of 48 farmers, their spouses, and their 79 children found that 60% of farmers had detectable levels of glyphosate in their urine. Farmers who wore rubber gloves had less glyphosate in their urine, and farmers who made skin contact with the glyphosate had more. A small percent of spouses and children also had low levels of glyphosate in their urine, but this mostly seemed to happen when the spouses or children helped prepare the glyphosate formulation or apply it to the fields. Despite this direct exposure, farmers are not especially obese.

Maybe glyphosate (or some other pesticide) degrades over time, or combines with something else in the environment, and ends up forming some byproduct that causes obesity? Again this seems unlikely. If some byproduct of a chemical used at farms caused obesity, you would think that the people who spend all their time at the farm would get the most exposure. There are some exceptions — farm workers probably don’t get much exposure to the antibiotics given to livestock, for example — but it seems unavoidable in the case of contaminants that are sprayed directly on fields.

Maybe eating glyphosate-laced food is different from inhaling glyphosate or absorbing it through your skin. This seems possible, given that there are some signs glyphosate might disrupt the microbiome, and this could potentially explain why farmers are not all that obese, since they’re not eating the stuff. But once again this seems unlikely, because there are major differences between obesity rates for other professions.

Motor vehicle operators, healthcare workers, and law enforcement workers are some of the professions with the highest levels of obesity. Teachers, design workers, and legal workers are some of the professions with the lowest levels of obesity. Some of these differences are very robust. 

This seems hard to reconcile with an account where glyphosate, or a glyphosate byproduct, causes obesity. Granted, glyphosate is used other places than just on farms. But why would truck drivers and police officers be exposed to so much more glyphosate than everyone else? How could they be exposed to more than farm workers? It’s possible that there is something about driving a truck that unlocks the harmful potential of glyphosate (or something about glyphosate that unlocks the harmful potential of being a truck driver) but at the moment this seems unlikely.

Like farmers, forestry workers also work with glyphosate. But despite this, forestry workers involved in spraying don’t show any glyphosate in their urine, despite clearly getting it on their clothes and even on their skin. It’s hard to see how law enforcement workers or truck drivers could be getting an appreciable dose of glyphosate when forestry workers who handle the stuff directly don’t seem to get any in their body. And, we can note, forestry worker is a pretty lean profession as well.

While the geographic match is pretty good in the US, the international match is mixed. We haven’t been able to find the clearest sources, but here’s a map from one paper: 

Compared to:

If glyphosate were a major driver of obesity, we would expect Central and South America and the Middle East to be much less obese. We would expect Spain, Germany, Poland, and much of Africa to be much more obese. Food imports and differences in water treatment techniques may be able explain some of this, but it’s not an immediate hit for glyphosate. 

Direct Evidence

If you look into a potential glyphosate-obesity connection you will eventually find a 2014 paper titled Genetically Engineered Crops, Glyphosate and the Deterioration of Health in the United States of America, or sources based on it, so we need to address it here. 

This paper reports an absolutely comically huge correlation of 0.962 between glyphosate application and obesity, and similarly enormous correlations with other diseases. This correlation is implausibly large, and it is not accurate — it is the result of a common error people make when working with time series data.

A good explanation of this error can be found in Avoiding Common Mistakes with Time Series Analysis by Tom Fawcett, where he shows that adding a slight trend to two totally random, unrelated time series ends up making them appear extremely correlated despite the total lack of a relationship. In his example, the apparent correlation ends up being .96, despite the true correlation being zero. What this paper reports is not evidence that glyphosate causes obesity, it is only evidence that glyphosate use has increased since 1996 (we already knew that) and that obesity has also increased since 1996 (we already knew that too).

There is some evidence of weight loss, or at least “decreased body weight gain”, in animal studies. All these studies are in rats and mice, however, and this seems to happen only at the highest doses. When we say “highest doses”, we mean really high — in one study the highest dose was 1183 mg/kg/day, in another it was ​​3500 mg/kg/day, in a third it was 4945-6069 mg/kg/day. 

In comparison, the U.S. Environmental Protection Agency reference dose for glyphosate in humans, “or estimate of daily exposure that would not cause adverse effects throughout a lifetime”, is 2 mg/kg/day. In that study from before, the highest estimated systemic dose in farmers who were working directly with glyphosate was only 0.004 mg/kg.

This is a tiny bit of evidence for glyphosate causing weight change, but it’s 1) in animals, 2) weight loss rather than weight gain, and 3) only at doses about 1000 times higher than recommended and about 250,000 times higher than the doses found in people who work with glyphosate directly.

The best evidence for glyphosate causing weight gain that we could find was from a 2019 study in rats. In this study, they exposed female rats (the original generation, F0) to 25 mg/kg body weight glyphosate daily, during days 8 to 14 of gestation. There was essentially no effect of glyphosate exposure on these rats, or in their children (F1), but there was a significant increase in the rates of obesity in their grandchildren (F2) and great-grandchildren (F3). There are some multiple comparison issues, but the differences are relatively robust, and are present in both male and female descendants, so we’re inclined to think that there’s something here.

There are a few problems with extending these results to humans, however, and we don’t just mean that the study subjects are all rats. The dose they give is pretty high, 25 mg/kg/day, in comparison to (again) farmers working directly with the stuff getting a dose closer to 0.004 mg/kg.

The timeline also doesn’t seem to line up. If we take this finding and apply it to humans at face value, glyphosate would only make you obese if your grandmother or great-grandmother was exposed during gestation. But glyphosate wasn’t brought to market until 1974 and didn’t see much use until the 1990s. There are some grandparents today who could have been exposed when they were pregnant, but obesity began rising in the 1980s. If glyphosate had been invented in the 1920s, this would be much more concerning, but it wasn’t.

Conclusions

It doesn’t look like glyphosate can be a major contributor to the obesity epidemic. It was introduced slightly before obesity began to skyrocket, but it didn’t see much use until decades later. It seems to have arrived too late to be responsible. There may be a slim chance that glyphosate contributes in some small way to obesity, and might be responsible for some of the increase in obesity since the mid-90s, but it doesn’t look like it could have started the epidemic.

Glyphosate exposure doesn’t seem to match international patterns of obesity, and glyphosate doesn’t seem to be able to explain the variation in obesity rates by profession. If glyphosate caused obesity, we would expect farm and forestry workers to have high levels of obesity, but in fact their obesity rates are pretty average, or even below average. Finally, there’s very limited evidence of glyphosate exposure causing weight change in animals, and no evidence in humans, at least none that we can find.

To us, it doesn’t seem likely that glyphosate plays any serious role in the obesity epidemic, and it probably doesn’t play any role at all. If you disagree or have any evidence to the contrary, however, please let us know!

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[Next Time: SEED OILS]

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[PART I – MYSTERIES]
[PART II – CURRENT THEORIES OF OBESITY ARE INADEQUATE]
[PART III – ENVIRONMENTAL CONTAMINANTS]
[INTERLUDE A – CICO KILLER, QU’EST-CE QUE C’EST?]
[PART IV – CRITERIA]
[PART V – LIVESTOCK ANTIBIOTICS]
[INTERLUDE B – THE NUTRIENT SLUDGE DIET]
[PART VI – PFAS]

Lithium is the third element on the periodic table, the lightest metal, a hit Nirvana single, and a mood-stabilizing drug often used to treat bipolar disorder.

Lithium isn’t synthetic, of course, but it can still be an environmental contaminant. While it occurs naturally in small concentrations in groundwater, human activity might have led to serious increases over the past few decades.

Unlike the other contaminants we’ve reviewed, we don’t need to spend any time convincing you that lithium makes people gain weight: it does. Almost everyone who takes lithium at therapeutic levels gains some weight. About half of them report serious weight gain, on average 22 lbs (10kg), and about 20% of patients gain more than that. Weight gained is correlated (r = .44, p < .001) with dosage. Unsurprisingly, weight gain on lithium is related to an increase in leptin levels.

We’d love to tell you whether lithium concentrations in groundwater have increased over time. But while lithium is easy to detect, assessing lithium levels is not a part of the standard analysis of drinking water, so we don’t have reliable historical data to work with. There aren’t even EPA standards for lithium levels in drinking water.

We’d also like to tell you about how much lithium people are exposed to, and whether that has increased over the past several decades. Measuring serum lithium is relatively easy, and people who are starting lithium treatment get checked frequently to make sure that their blood levels aren’t too high. Despite this, there doesn’t seem to be any data on serum lithium levels in the general population. The NHANES data has records of how much uranium there was in your urine every year from 2000-2016, but not a single measure related to lithium. Great job, guys.

We can’t talk about trends in the groundwater or in people’s bodies directly. But what we can do is look at other trends that we would expect to be related. For example, this figure shows a graph of USGS-reported records for global lithium production since 1900:

This graph is pretty telling. Almost no lithium was produced before 1950, so human activity couldn’t have been adding a meaningful amount to the groundwater back then. Serious lithium production started around 1950, which could help explain why obesity went from about 3% in 1890 to about 10% in 1980, but we see that lithium production truly spikes around 1980. While there have been a few ups and downs, production has as a rule continued to rise ever since. This graph only goes up to 2007, but USGS and other sources confirm that production has continued to increase, at about 11% per year from 2007 to 2017.

Lithium definitely ends up in the groundwater. It’s there in small concentrations naturally, but human activity adds more. In Seoul, South Korea, lithium concentrations sextuple as the Han river passes through the city’s densest districts. This is reflected not only in the river, but also in the tap water in the city — tap water from sites further along the river’s course have similarly elevated lithium levels.

This suggests that rivers pick up lithium along their course and generally have higher lithium levels as they flow downhill. This is supported by data from Austria, which shows that lithium levels in drinking water vary systematically with altitude, with higher concentrations of lithium found in districts at lower altitudes:

We should note that a paper looking at groundwater in the United States from 1992-2003 found the opposite effect: higher levels of lithium at higher altitudes. “However,” they say, “these findings should be interpreted with caution.” We agree. There are 3,141 counties in the United States, and they only looked at data from 518. They only examined data from 15 states, most of them states at relatively low elevation. These weren’t randomly selected, either; they were the sites with the highest number of lithium samples in the years 1992-2003.

We’ve already discussed the issues that come up when you conduct analysis on a restricted range of data. Further, the Seoul data shows that lithium levels spike around urban areas. If some of the high-altitude measurements were near or immediately downstream from cities or manufacturing areas, that might make it look like higher-altitude locations have higher levels of lithium on average.

Dosage

The therapeutic dose of lithium in blood serum is usually considered to be in the range of 0.8 – 1.2 mmol/L, though some sources suggest that lower doses are more effective, with the “minimum efficacious serum lithium level” being possibly as low as 0.4 mmol/L. To translate these to more familiar terms, 0.8 mmol/L is about 5600 ng/mL, and 0.4 mmol/L is about 2800 ng/mL.

That’s quite a lot. In comparison, lithium levels in groundwater rarely exceed 200 ng/mL. But perhaps surprisingly, even very low levels can have an influence on our health and mental states. One study examining data from 27 Texas counties between 1978-1987 found that rates of suicide and homicide (as well as other forms of violent and impulsive behavior) were negatively correlated with lithium in drinking water, over water lithium levels ranging from 70 to 170 ng/mL. Another study looking at various cities in Lithiuania (no relation to lithium) found a negative relationship between lithium exposure and suicide. The lithium levels in the public drinking water systems they examined ranged from 0.5 to 35.5 ng/mL, with a median level of 3.6 ng/mL. In general, reviews of this literature find that trace levels of lithium have a meaningful impact on behavior.

There’s only one randomized controlled trial examining the effects of trace amounts of lithium, but it finds the same thing. A group of former drug users (heroin, crystal meth, PCP, and cocaine), most of them with a history of violent crime or domestic violence, were given either 400 µg per day of lithium orally, or a placebo. For comparison, a normal clinical dose is 300,000 – 600,000 µg, taken two to three times per day. Even on this comparatively tiny dose, everyone in the lithium group reported feeling happier, more friendly, more kind, less grouchy, etc. over a four week period, “without exception”. 

(These former drug users didn’t have normal moods to begin with — one said “I am always extremely moody and fight with my girlfriend frequently” before he was treated — so it’s not clear if trace amounts of lithium would improve mood in everyone else. Similarly, therapeutic doses are only given to patients with bipolar disorder, and it’s not clear what the effects would be on someone without this diagnosis.)

In the placebo group, people were just about as grouchy as before. When they switched the placebo group over to lithium, these people responded in exactly the same way.

This is pretty strong evidence that even very small doses of lithium can have meaningful effects. So should we be surprised that they don’t mention any weight gain? There isn’t much data on the time course of weight gain in lithium treatment, but it seems to come on pretty fast. In one study with normal therapeutic doses, 15 bipolar inpatients gained an average of 13 lbs (5.9 kg) over six weeks. While the sample size is quite small, this tells us that sometimes a lot of weight gain can happen fast.

We don’t think this is a huge problem. The randomized controlled trial on trace exposure only lasted a couple of weeks. Even if patients were gaining weight at the same rate as patients on a therapeutic dose, they might not have noticed. The researchers didn’t intend to examine weight gain, and probably didn’t measure it. They don’t report any other side effects. Heroin, crystal meth, PCP, and cocaine all make people lose weight, so it’s possible that weight gain in the former drug users would be seen as a sign of health. It’s also worth noting that while these trace amounts do appear to have real, consequential effects, the dosage was about 1,000 times smaller than a therapeutic dose. In this situation, it’s not crazy to think that weight gain might take a few weeks or even months to manifest. We see a version of the main effect — improved mood — in this tiny dose. It seems reasonable that we might see a version of this side effect as well.

This study can give us a lower limit not only of the dosage, but by extension, of the minimum effective serum level. As a ballpark estimate, therapeutic dosages are in the range of 1,000,000 µg per day and they lead to serum levels of around 5000 ng/mL. This means the 400 µg per day dose from the randomized controlled trial would lead to a serum level of around 2 ng/mL. Other sources suggest that blood levels may end up slightly higher on low doses. For example, doses in the range of 385 to 1540 µg per day lead to serum levels around 7 to 28 ng/mL. One study testing serum lithium as a compliance marker for food and supplement intake found that giving people lithium-tagged yogurt with a dose of about 1000 µg per day over a period of six weeks led to an increase in serum levels from 6 ng/mL to 46 ng/mL.

These papers disagree on the specifics but they agree on the general picture. A serum level in the range of 10 ng/mL is enough to influence mood, and a dose of about 400 µg per day is enough to get you there. Whether lower doses have an effect is unclear, but we should certainly be interested in numbers in these ranges and up.

Trace Exposure

There aren’t any other randomized controlled trials, but if trace amounts are enough to cause obesity, then we should see relationships between trace lithium levels and obesity rates.

In Texas, a survey of mean lithium levels in public wells across 226 counties (Texas has 254 in total) found lithium levels ranging from 2.8 to 219.0 ng/mL. Now Texas is not one of the most obese states — but it tends to be more obese along its border with Lousiana, which is also where the highest levels of lithium were reported.

West Virginia and Alabama, on the other hand, are two of the most obese states in the nation. We haven’t been able to find any reliable groundwater concentration data for these states, but we can certainly note that both of them have problems with lithium contamination coming from local mining operations. And it’s not just Alabama and West Virginia — other states are facing similar contamination.

In Greece, lithium levels in drinking water range from 0.1 ng/mL in Chios island to 121 ng/mL on the island of Samos, with an average of 11.1 ng/mL. Unfortunately there’s not much data on the prevalence of obesity in Greece, but we can conduct some due diligence by checking a few of these endpoints. Samos, with the highest levels, is the obvious place to start. On Samos, 10.7% of children aged 3-12 are overweight, compared to 6.5% on the island of Corfu. A full 27% of high schoolers on Samos island were overweight in 2010, and 12.4% were obese. In comparison, about 12.5% of American high schoolers were obese in the same period.

In the Caspian Sea, lithium concentrations are 280 ng/mL. As we’ve already reviewed, some of the most obese provinces in Iran border the Caspian. The Dead Sea has concentrations even higher, at 14,000 ng/mL, but for the obvious reasons, we don’t think people are getting a lot of their drinking water from the Dead Sea. On the other hand, obesity in the West Bank is pretty high — as high as 50% in men in 2003!

Very high concentrations of lithium have also been reported in Austria. For the most part, Austria has normal amounts of lithium in its drinking water, around 13 ng/mL. But in the east, the concentrations are much higher. In the Mistelbach district, the average level of lithium in the drinking water was 82 ng/mL, and the highest single measurement was near Graz, at 1300 ng/mL. Both of these are in eastern Austria, where obesity levels are highest. Mistelbach in particular is one of the most obese districts in the country.

Chile and Argentina are the most obese countries in South America (28% each) and are two of the biggest exporters of lithium in the world. Unsurprisingly, this is reflected in their groundwater.

In northern Chile, lithium levels in the groundwater can reach levels 10,000 times higher than normal. The rivers running through many small valleys see lithium concentrations of 600 – 1600 ng/mL. The drinking water in many towns has levels up to 700 ng/mL. And in the headwaters of the Rio Camerones, lithium hits concentrations of 24,880 ng/mL. In 1980, Zaldivar reported similar levels of lithium in the groundwater, stating that they were “the highest reported in the world”. He also measured serum levels in people at these different sites, and found values ranging from 22.3 ng/mL to 85.8 ng/mL.

(“We tried to find Zaldivar to learn more about his work,” says a later paper, “but to no avail. He left Chile when Pinochet came to power and effectively disappeared.”)

In Argentina, lithium can reach up to 1000 ng/mL in drinking water, and the locals end up with a lot of exposure. At the site with the highest levels, lithium concentrations reached an average of 4,550 ng/mL in people’s urine. The highest level in someone’s urine was actually a whopping 14,300 ng/mL. The locals seem to be getting much of their lithium exposure from their tap water, as the amount of lithium in urine was correlated with the number of glasses of water consumed per day (r = 0.173, p = 0.029).

These are all freshwater levels. In seawater, lithium concentrations are reliably quite high, ranging from 100 ng/mL to over 1000 ng/mL. Now, most people are not actually drinking meaningful amounts of seawater, but if you live near the ocean, you might still be exposed indirectly.

One mystery we haven’t mentioned yet is that the Middle East is extremely obese (see map below), one of the most obese regions on earth. Jordan, Qatar, Libya, Egypt, Lebanon, and Saudi Arabia all barely trail the United States in terms of obesity, and Kuwait is actually slightly more obese than the United States, about 38% obese compared to 36% in America. These countries are very dry, and so all of them get a lot of drinking water from desalinated seawater. Saudi Arabia gets about half of its drinking water from desalination and is one of the most obese nations on earth. Kuwait built its first desalination plant in 1951, and has actually been one of the most obese countries in the world for a long time. Back in 1975, when the rate of obesity in the United States was around 10%, the rate of obesity in Kuwait was about 18%.

Desalination removes all trace elements from seawater, but because distilled water corrodes metal pipes and trace elements are important to health, the desalinated water is remineralized by blending it with 5-10% brackish water. This means that desalinated water could easily have lithium concentrations of up to 100 ng/mL. Unlike contamination in some forms of drinking water, which might vary with factors like rainfall and industrial activity, we would expect lithium levels to be reliably high in desalinated water, because they are inherent to the source.

We even have some data about lithium levels in the waters of the Persian Gulf. Near Qeshm island, at least, seawater concentrations vary somewhat by season but are usually around 300 ng/mL. This is reasonably high for seawater and much higher than the levels usually observed in groundwater. Not all of that makes it back into the water after desalination, of course, but even if only 10% got back in, 30 ng/mL is still a pretty high dose to be receiving regularly.

(If you are a Kuwaiti or Saudi desalination engineer, please contact us! This blog has gotten 15 views from Kuwait and 26 from Saudi Arabia, we know you’re out there!)

In any case, if lithium from desalinated seawater doesn’t explain why the Middle East has such incredibly high rates of obesity, then some other explanation will have to be found for this extremely striking observation.

On average, people drink about 3 liters of water per day. If they’re drinking from a normal freshwater source with 1-10 ng/mL, they’ll get a dose of about 3-30 µg / day. If they’re drinking from desalinated seawater, with concentrations of about 30-100 ng/mL, they’ll get a dose of about 90-300 µg / day. If they’re drinking from sources like those found in Texas, Greece, and Mistelbach, with concentrations of about 100-200 ng/mL, they’ll get a dose of about 300-600 µg / day. If they’re drinking from sources like those found in Graz, Chile, and Argentina, with 1000 ng/mL, they’ll easily get a dose of 3000 µg / day or more:

In comparison, therapeutic doses are in the range of 1,000,000 µg per day, but remember the randomized controlled trial showed effects at only 400 µg per day. Many people are getting doses of similar amounts from their drinking water alone. And this is assuming that they’re not also exposed to lithium in other ways.

Common Uses of Lithium

Which they probably are, because lithium has a wide variety of applications. In 2017, the USGS estimated that 48% of the global market for lithium was batteries, 26% was ceramics and glass, 7% was lubricating greases, the remainder being industrial uses like polymer production and air treatment. They also mention a couple uses like “agrochemicals”, airbag ignition, aluminum alloys, cement and concrete additives, and dyes and pigments.

You’ll remember from our review in the PFAS section that some of the most obese professions include firefighters, cooks, food workers, cleaning workers, motor vehicle operators, vehicle mechanics, transportation and material moving, healthcare support, health technicians, and some construction occupations (“Helpers, construction trades” and “Other construction and related workers”).

If you go and see your local auto mechanic, the black smears covering his hands and forearms might be engine oil. But they might also be lithium grease. This grease is ubiquitous in auto engineering, routinely applied to hinges, joints, and pivot points. It’s used in aviation and on many kinds of heavy machinery, including logging and construction equipment, trains, and tractors. It also has a number of household applications. You might put it on your garage door, or the hinges on the gate of your fence. About 7% of the global supply of lithium goes into lubricating greases of one kind or another. That’s a lot of grease.

In addition to any lithium they’re exposed to in their food and water, vehicle mechanics, truck drivers, and transportation workers are also constantly exposed to lithium grease at work. They may literally be rubbing the grease all over their hands. Like any grease, this is hard to get off your skin, in most cases requiring a special soap. Hopefully they keep it out of their eyes and mouth, but even so, it doesn’t seem like it would be great for you.

Construction workers also use lithium grease to lubricate their tools and equipment. They may be exposed through lithium added to concrete and cement. Lithium is used in agrochemicals like pesticides, though information on exactly what agrochemicals this includes is spotty. It’s possible that this explains the higher levels of obesity in cooks and food workers.

Lithium grease isn’t considered food-safe, and in theory it shouldn’t be used on food-handling equipment. In practice, however, manufacturers and restaurants don’t always follow regulations. A quick Google search reveals incidents like lithium grease being stored with food equipment, lithium grease being stored next to garlic bulbs, and lithium grease being stored above mustard.

It’s not clear if there’s a connection with healthcare professionals, firefighters, or cleaning workers. Maybe there’s a hidden lithium connection out there. But there doesn’t have to be. Lithium may just be part of the story — the rest could be explained by other contaminants, like PFAS.

And speaking of PFAS, there’s actually a connection. Lithium greases often include other substances to improve their performance, including Teflon, aka PTFE.

Bioaccumulation

One strike against lithium as an explanation for the obesity epidemic is that it only stays in the body for a few days, with a half-life of 18-36 hours. The medical consensus seems to be that it probably doesn’t bioaccumulate.

But this may not be a problem, for a few reasons. First, lithium may be able to affect weight without accumulating in the body. One possible mechanism by which environmental contaminants could cause obesity is by interfering with the microbiome. If exposure to lithium changes the composition of your gut microbiota, then exposure to lithium could have serious impacts on your weight without any bioaccumulation. Even brief exposure to lithium could have long-lasting effects. And in fact there is evidence that dietary lithium affects the microbiome, at least in rats.

Second, the medical consensus might simply be wrong. While lithium is traditionally measured in the serum, this may not be the best way to evaluate bioaccumulation. “In contrast to other psychotherapeutic drugs,” says one paper on the pharmacokinetics of lithium, “Li+ is fairly evenly distributed in the body, but in tissues such as the white matter of the brain, the bones, and in the thyroid gland the concentrations per kg wet weight are about twice those in the serum.” 

A particularly interesting example is a case study of a patient who died after lithium poisoning. Researchers found that most tissue samples (“liver, spleen, kidney, lung, muscle, cardiac muscle, pancreas”) contained about the same concentration of lithium as found in the serum, in the range of 0.4-0.6 mmol/kg. But in the thyroid gland and in brain tissue (especially white matter), lithium concentrations were nearly twice as high as in serum, in the range of 0.7-0.8 mmol/kg. They suggest that this is to be expected, saying, “lithium has an increased affinity to thyroid tissue,” and, “high concentrations of lithium in brain tissue – especially in white substance – agrees with investigations that reveal the lithium elimination from brain tissue to be slow.”

This is particularly interesting not only because it seems to show evidence of bioaccumulation, but because of the particular tissues in which concentrations were found to be highest. The thyroid gland is very important to weight regulation, and so to find that lithium concentrations in that organ were second-highest in the body is very neatly in line with our expectations. Maybe it shouldn’t be a surprise, because lithium therapy is associated with thyroid disease.

For a while this was the best evidence of lithium accumulation in the brain, but a few weeks ago our friend Dr. Grace Rosen sent us this Nature paper published in March 2021. In this paper, the authors took 139 brain samples from three deceased individuals and took them to a nuclear reactor in Bavaria, where they were placed in a chamber and shot with a “well focused beam of cold neutrons with a neutron flux of ɸ = 1.2 × 10¹⁰ cm⁻² s⁻¹”. The lithium-neutron interaction gives a unique “associated coincident energy pattern”, which allowed them to measure the amount of lithium at different sites in the brains. Unsurprisingly, the patient receiving lithium therapy at the time of death had the highest concentration, but the brains of the other two individuals did as well, presumably from trace exposure.

Just like the case study above, they found that lithium was more concentrated in white than in gray matter. Additionally, the authors note that lithium concentrations were especially high in the thalamus and Brodmann Area 25. This is interesting for our purposes because Brodmann Area 25 “influences changes in appetite and sleep” and the thalamus governs “sensory relay in visual, auditory, somatosensory, and gustatory systems.” Both of these brain regions are related to eating behavior.

Sadly the authors did not examine any samples from the hypothalamus, which governs eating more directly, but this is still evidence that trace lithium bioaccumulates in brain regions that are important to the regulation of food intake and body weight.

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