A Fatal Case of Nutritionism
The concept of 'nutritionism' was developed by Dr. Gyorgy Scrinis and popularized by the food writer Michael Pollan. It states that the health value of a food can be guessed by the sum of the nutrients it contains. Pollan argues, I think rightfully, that nutritionism is a reductionist philosophy that assumes we know more about food composition and the human body than we actually do. You can find varying degrees of this philosophy in most mainstream discussions of diet and health*.
One conspicuous way nutritionism manifests is in the idea that saturated fat is harmful. Any fat rich in saturated fatty acids is typically assumed to be unhealthy, regardless of its other constituents. There is also apparently no need to directly test that assumption, or even to look through the literature to see if the assumption has already been tested. In this manner, 'saturated' tropical plant fats such as palm oil and coconut oil have been labeled unhealthy, despite essentially no direct evidence that they're harmful. As we'll see, there is actually quite a bit of evidence, both indirect and direct, that their unrefined forms are not harmful and perhaps even beneficial.
Palm Oil and Heart Disease
Long-time readers may recall a post I wrote a while back titled Ischemic Heart Attacks: Disease of Civilization (1). I described a study from 1964 in which investigators looked for signs of heart attacks in thousands of consecutive autopsies in the US and Africa, among other places. They found virtually none in hearts from Nigeria and Uganda (3 non-fatal among more than 4,500 hearts), while Americans of the same age had very high rates (up to 1/3 of hearts).
What do they eat in Nigeria? Typical Nigerian food involves home-processed grains, starchy root vegetables, beans, fruit, vegetables, peanuts, red palm oil, and a bit of dairy, fish and meat**. The oil palm Elaeis guineensis originated in West Africa and remains one of the main dietary fats throughout the region.
To extract the oil, palm fruit are steamed, and the oily flesh is removed and pressed. It's similar to olive oil in that it is extracted gently from an oil-rich fruit, rather than harshly from an oil-poor seed (e.g., corn or soy oil). The oil that results is deep red and is perhaps the most nutrient-rich fat on the planet. The red color comes from carotenes, but red palm oil also contains a large amount of vitamin E (mostly tocotrienols), vitamin K1, coenzyme Q10 and assorted other fat-soluble constituents. This adds up to a very high concentration of fat-soluble antioxidants, which are needed to protect the fat from rancidity in hot and sunny West Africa. Some of these make it into the body when it's ingested, where they appear to protect the body's own fats from oxidation.
Mainstream nutrition authorities state that palm oil should be avoided due to the fact that it's approximately half saturated. This is actually one of the main reasons palm oil was replaced by hydrogenated seed oils in the processed food industry. Saturated fat raises blood cholesterol, which increases the risk of heart disease. Doesn't it? Let's see what the studies have to say.
Most of the studies were done using refined palm oil, unfortunately. Besides only being relevant to processed foods, this method also introduces a new variable because palm oil can be refined and oxidized to varying degrees. However, a few studies were done with red palm oil, and one even compared it to refined palm oil. Dr. Suzanna Scholtz and colleagues put 59 volunteers on diets predominating in sunflower oil, refined palm oil or red palm oil for 4 weeks. LDL cholesterol was not different between the sunflower oil and red palm oil groups, however the red palm oil group saw a significant increase in HDL. LDL and HDL both increased in the refined palm oil group relative to the sunflower oil group (2).
Although the evidence is conflicting, most studies have not been able to replicate the finding that refined palm oil increases LDL relative to less saturated oils (3, 4). This is consistent with studies in a variety of species showing that saturated fat generally doesn't raise LDL compared to monounsaturated fat in the long term, unless a large amount of purified cholesterol is added to the diet (5).
Investigators have also explored the ability of palm oil to promote atherosclerosis, or hardening and thickening of the arteries, in animals. Not only does palm oil not promote atherosclerosis relative to monounsaturated fats (e.g., olive oil), but in its unrefined state it actually protects against atherosclerosis (6, 7). A study in humans hinted at a possible explanation: compared to a monounsaturated oil***, palm oil greatly reduced oxidized LDL (8). As a matter of fact, I've never seen a dietary intervention reduce oxLDL to that degree (69%). oxLDL is a major risk factor for cardiovascular disease, and a much better predictor of risk than the typically measured LDL cholesterol (9). The paper didn't state whether or not the palm oil was refined. I suspect it was lightly refined, but still rich in vitamin E and CoQ10.
As I discussed in my recent interview with Jimmy Moore, atherosclerosis is only one factor in heart attack risk (10). Several other factors are also major determinants of risk: clotting tendency, plaque stability, and susceptibility to arrhythmia. Another factor that I haven't discussed is how resistant the heart muscle is to hypoxia, or loss of oxygen. If the coronary arteries are temporarily blocked-- a frequent occurrence in modern people-- the heart muscle can be damaged. Dietary factors determine the degree of damage that results. For example, in rodents, nitrites derived from green vegetables protect the heart from hypoxia damage (11). It turns out that red palm oil is also protective (12, 13). Red palm oil also protects against high blood pressure in rats, an effect attributed to its ability to reduce oxidative stress (14, 15).
Together, the evidence suggests that red palm oil does not contribute to heart disease risk, and in fact is likely to be protective. The benefits of red palm oil probably come mostly from its minor constituents, i.e. the substances besides its fatty acids. Several studies have shown that a red palm oil extract called palmvitee lowers serum lipids in humans (16, 17). The minor constituents are precisely what are removed during the refining process.
Palm Oil and the Immune System
Red palm oil also has beneficial effects on the immune system in rodents. It protects against bacterial infection when compared with soybean oil (18). It also protects against certain cancers, compared to other oils (19, 20). This may be in part due to its lower content of omega-6 linoleic acid (roughly 10%), and minor constituents.
The Verdict
Yet again, nutritionism has gotten itself into trouble by underestimating the biological complexity of a whole food. Rather than being harmful to human health, red palm oil, an ancient and delicious food, is likely to be protective. It's also one of the cheapest oils available worldwide, due to the oil palm's high productivity. It has a good shelf life and does not require refrigeration. Its strong, savory flavor goes well in stews, particularly meat stews. It isn't available in most grocery stores, but you can find it on the internet. Make sure not to confuse it with refined palm oil or palm kernel oil.
* The approach that Pollan and I favor is a simpler, more empirical one: eat foods that have successfully sustained healthy cultures.
** Some Nigerians are also pastoralists that subsist primarily on dairy.
*** High oleic sunflower oil, from a type of sunflower bred to be high in monounsaturated fat and low in linoleic acid. I think it's probably among the least harmful refined oils. I use it sometimes to make mayonnaise. It's often available in grocery stores, just check the label.
Showing posts with label hypertension. Show all posts
Showing posts with label hypertension. Show all posts
Saturday, July 3, 2010
Thursday, June 10, 2010
Nitrate: a Protective Factor in Leafy Greens
Cancer Link and Food Sources
Nitrate (NO3) is a molecule that has received a lot of bad press over the years. It was initially thought to promote digestive cancers, in part due to its ability to form carcinogens in the digestive tract. As it's used as a preservative in processed meats, and there is a link between processed meats and gastric cancer (1), nitrate was viewed with suspicion and a number of countries imposed strict limits on its use as a food additive.
But what if I told you that by far the greatest source of nitrate in the modern diet isn't processed meat-- but vegetables, particularly leafy greens (2)? And that the evidence specifically linking nitrate consumption to gastric cancer has largely failed to materialize? For example, one study found no difference in the incidence of gastric cancer between nitrate fertilizer plant workers and the general population (3). Most other studies in animals and humans have not supported the hypothesis that nitrate itself is carcinogenic (4, 5, 6). This, combined with recent findings on nitrate biology, has the experts singing a different tune in the last few years.
A New Example of Human Symbiosis
In 2003, Dr. K. Cosby and colleagues showed that nitrite (NO2; not the same as nitrate) dilates blood vessels in humans when infused into the blood (7). Investigators subsequently uncovered an amazing new example of human-bacteria symbiosis: dietary nitrate (NO3) is absorbed from the gut into the bloodstream and picked up by the salivary glands. It's then secreted into saliva, where oral bacteria use it as an energy source, converting it to nitrite (NO2). After swallowing, the nitrite is reabsorbed into the bloodstream (8). Humans and oral bacteria may have co-evolved to take advantage of this process. Antibacterial mouthwash prevents it.
Nitrate Protects the Cardiovascular System
In 2008, Dr. Andrew J. Webb and colleagues showed that nitrate in the form of 1/2 liter of beet juice (equivalent in volume to about 1.5 soda cans) substantially lowers blood pressure in healthy volunteers for over 24 hours. It also preserved blood vessel performance after brief oxygen deprivation, and reduced the tendency of the blood to clot (9). These are all changes that one would expect to protect against cardiovascular disease. Another group showed that in monkeys, the ability of nitrite to lower blood pressure did not diminish after two weeks, showing that the animals did not develop a tolerance to it on this timescale (10).
Subsequent studies showed that dietary nitrite reduces blood vessel dysfunction and inflammation (CRP) in cholesterol-fed mice (11). Low doses of nitrite also dramatically reduce tissue death in the hearts of mice exposed to conditions mimicking a heart attack, as well as protecting other tissues against oxygen deprivation damage (12). The doses used in this study were the equivalent of a human eating a large serving (100 g; roughly 1/4 lb) of lettuce or spinach.
Mechanism
Nitrite is thought to protect the cardiovascular system by serving as a precursor for nitric oxide (NO), one of the most potent anti-inflammatory and blood vessel-dilating compounds in the body (13). A decrease in blood vessel nitric oxide is probably one of the mechanisms of diet-induced atherosclerosis and increased clotting tendency, and it is likely an early consequence of eating a poor diet (14).
The Long View
Leafy greens were one of the "protective foods" emphasized by the nutrition giant Sir Edward Mellanby (15), along with eggs and high-quality full-fat dairy. There are many reasons to believe greens are an excellent contribution to the human diet, and what researchers have recently learned about nitrate biology certainly reinforces that notion. Leafy greens may be particularly useful for the prevention and reversal of cardiovascular disease, but are likely to have positive effects on other organ systems both in health and disease. It's ironic that a molecule suspected to be the harmful factor in processed meats is turning out to be one of the major protective factors in vegetables.
Nitrate (NO3) is a molecule that has received a lot of bad press over the years. It was initially thought to promote digestive cancers, in part due to its ability to form carcinogens in the digestive tract. As it's used as a preservative in processed meats, and there is a link between processed meats and gastric cancer (1), nitrate was viewed with suspicion and a number of countries imposed strict limits on its use as a food additive.
But what if I told you that by far the greatest source of nitrate in the modern diet isn't processed meat-- but vegetables, particularly leafy greens (2)? And that the evidence specifically linking nitrate consumption to gastric cancer has largely failed to materialize? For example, one study found no difference in the incidence of gastric cancer between nitrate fertilizer plant workers and the general population (3). Most other studies in animals and humans have not supported the hypothesis that nitrate itself is carcinogenic (4, 5, 6). This, combined with recent findings on nitrate biology, has the experts singing a different tune in the last few years.
A New Example of Human Symbiosis
In 2003, Dr. K. Cosby and colleagues showed that nitrite (NO2; not the same as nitrate) dilates blood vessels in humans when infused into the blood (7). Investigators subsequently uncovered an amazing new example of human-bacteria symbiosis: dietary nitrate (NO3) is absorbed from the gut into the bloodstream and picked up by the salivary glands. It's then secreted into saliva, where oral bacteria use it as an energy source, converting it to nitrite (NO2). After swallowing, the nitrite is reabsorbed into the bloodstream (8). Humans and oral bacteria may have co-evolved to take advantage of this process. Antibacterial mouthwash prevents it.
Nitrate Protects the Cardiovascular System
In 2008, Dr. Andrew J. Webb and colleagues showed that nitrate in the form of 1/2 liter of beet juice (equivalent in volume to about 1.5 soda cans) substantially lowers blood pressure in healthy volunteers for over 24 hours. It also preserved blood vessel performance after brief oxygen deprivation, and reduced the tendency of the blood to clot (9). These are all changes that one would expect to protect against cardiovascular disease. Another group showed that in monkeys, the ability of nitrite to lower blood pressure did not diminish after two weeks, showing that the animals did not develop a tolerance to it on this timescale (10).
Subsequent studies showed that dietary nitrite reduces blood vessel dysfunction and inflammation (CRP) in cholesterol-fed mice (11). Low doses of nitrite also dramatically reduce tissue death in the hearts of mice exposed to conditions mimicking a heart attack, as well as protecting other tissues against oxygen deprivation damage (12). The doses used in this study were the equivalent of a human eating a large serving (100 g; roughly 1/4 lb) of lettuce or spinach.
Mechanism
Nitrite is thought to protect the cardiovascular system by serving as a precursor for nitric oxide (NO), one of the most potent anti-inflammatory and blood vessel-dilating compounds in the body (13). A decrease in blood vessel nitric oxide is probably one of the mechanisms of diet-induced atherosclerosis and increased clotting tendency, and it is likely an early consequence of eating a poor diet (14).
The Long View
Leafy greens were one of the "protective foods" emphasized by the nutrition giant Sir Edward Mellanby (15), along with eggs and high-quality full-fat dairy. There are many reasons to believe greens are an excellent contribution to the human diet, and what researchers have recently learned about nitrate biology certainly reinforces that notion. Leafy greens may be particularly useful for the prevention and reversal of cardiovascular disease, but are likely to have positive effects on other organ systems both in health and disease. It's ironic that a molecule suspected to be the harmful factor in processed meats is turning out to be one of the major protective factors in vegetables.
Tuesday, April 6, 2010
Copper and Cardiovascular Disease
In 1942, Dr. H. W. Bennetts dissected 21 cattle known to have died of "falling disease". This was the name given to the sudden, inexplicable death that struck herds of cattle in certain regions of Australia. Dr. Bennett believed the disease was linked to copper deficiency. He found that 19 of the 21 cattle had abnormal hearts, showing atrophy and abnormal connective tissue infiltration (fibrosis) of the heart muscle (1).
In 1963, Dr. W. F. Coulson and colleagues found that 22 of 33 experimental copper-deficient pigs died of cardiovascular disease. 11 of 33 died of coronary heart disease, the quintessential modern human cardiovascular disease. Pigs on a severely copper-deficient diet showed weakened and ruptured arteries (aneurysms), while moderately deficient pigs "survived with scarred vessels but demonstrated a tendency toward premature atherosclerosis" including foam cell accumulation (2). Also in 1963, Dr. C. R. Ball and colleagues published a paper describing blood clots in the heart and coronary arteries, heart muscle degeneration, ventricular calcification and early death in mice fed a lard-rich diet (3).
This is where Dr. Leslie M. Klevay enters the story. Dr. Klevay suspected that Ball's mice had suffered from copper deficiency, and decided to test the hypothesis. He replicated Ball's experiment to the letter, using the same strain of mice and the same diet. Like Ball, he observed abnormal clotting in the heart, degeneration and enlargement of the heart muscle, and early death. He also showed by electrocardiogram that the hearts of the copper-deficient mice were often contracting abnormally (arrhythmia).
But then the coup de grace: he prevented these symptoms by supplementing the drinking water of a second group of mice with copper (4). In the words of Dr. Klevay: "copper was an antidote to fat intoxication" (5). I believe this was his tongue-in-cheek way of saying that the symptoms had been misdiagnosed by Ball as due to dietary fat, when in fact they were due to a lack of copper.
Since this time, a number of papers have been published on the relationship between copper intake and cardiovascular disease in animals, including several showing that copper supplementation prevents atherosclerosis in one of the most commonly used animal models of cardiovascular disease (6, 7, 8). Copper supplementation also corrects abnormal heart enlargement-- called hypertrophic cardiomyopathy-- and heart failure due to high blood pressure in mice (9).
For more than three decades, Dr. Klevay has been a champion of the copper deficiency theory of cardiovascular disease. According to him, copper deficiency is the only single intervention that has caused the full spectrum of human cardiovascular disease in animals, including:
The second reason you may not have heard of the theory is due to a lab assay called copper-mediated LDL oxidation. Researchers take LDL particles (from blood, the same ones the doctor measures as part of a cholesterol test) and expose them to a high concentration of copper in a test tube. Free copper ions are oxidants, and the researchers then measure the amount of time it takes the LDL to oxidize. I find this assay tiresome, because studies have shown that the amount of time it takes copper to oxidize LDL in a test tube doesn't predict how much oxidized LDL you'll actually find in the bloodstream of the person you took the LDL from (10, 11).
In other words, it's an assay that has little bearing on real life. But researchers like it because for some odd reason, feeding a person saturated fat causes their LDL to be oxidized more rapidly by copper in a test tube, even though that's not the case in the actual bloodstream (12). Guess which result got emphasized?
The fact that copper is such an efficient oxidant has led some researchers to propose that copper oxidizes LDL in human blood, and therefore dietary copper may contribute to heart disease (oxidized LDL is a central player in heart disease-- read more here). The problem with this theory is that there are virtually zero free copper ions in human serum. Then there's the fact that supplementing humans with copper actually reduces the susceptibility of red blood cells to oxidation (by copper in a test tube, unfortunately), which is difficult to reconcile with the idea that dietary copper increases oxidative stress in the blood (13).
The third reason you may never have heard of the theory is more problematic. Several studies have found that a higher level copper in the blood correlates with a higher risk of heart attack (14, 15). At this point, I could hang up my hat, and declare the animal experiments irrelevant to humans. But let's dig deeper.
Nutrient status is sometimes a slippery thing to measure. As it turns out, serum copper isn't a good marker of copper status. In a 4-month trial of copper depletion in humans, blood copper stayed stable, while the activity of copper-dependent enzymes in the blood declined (16). These include the important copper-dependent antioxidant, superoxide dismutase. As a side note, lysyl oxidase is another copper-dependent enzyme that cross-links the important structural proteins collagen and elastin in the artery wall, potentially explaining some of the vascular consequences of copper deficiency. Clotting factor VIII increased dramatically during copper depletion, perhaps predicting an increased tendency to clot. Even more troubling, three of the 12 women developed heart problems during the trial, which the authors felt was unusual:
Only a few studies have looked at the relationship between more accurate markers of copper status and cardiovascular disease in humans. Leukocyte copper status, a marker of tissue status, is lower in people with cardiovascular disease (22, 23). People who die of heart attacks generally have less copper in their hearts than people who die of other causes, although this could be an effect rather than a cause of the heart attack (24). Overall, I find the human data lacking. I'd like to see more studies examining liver copper status in relation to cardiovascular disease, as the liver is the main storage organ for copper.
According to a 2001 study, the majority of Americans may have copper intakes below the USDA recommended daily allowance (25), many substantially so. This problem is exacerbated by the fact that copper levels in food have declined in industrial nations over the course of the 20th century, something I'll discuss in the next post.
In 1963, Dr. W. F. Coulson and colleagues found that 22 of 33 experimental copper-deficient pigs died of cardiovascular disease. 11 of 33 died of coronary heart disease, the quintessential modern human cardiovascular disease. Pigs on a severely copper-deficient diet showed weakened and ruptured arteries (aneurysms), while moderately deficient pigs "survived with scarred vessels but demonstrated a tendency toward premature atherosclerosis" including foam cell accumulation (2). Also in 1963, Dr. C. R. Ball and colleagues published a paper describing blood clots in the heart and coronary arteries, heart muscle degeneration, ventricular calcification and early death in mice fed a lard-rich diet (3).
This is where Dr. Leslie M. Klevay enters the story. Dr. Klevay suspected that Ball's mice had suffered from copper deficiency, and decided to test the hypothesis. He replicated Ball's experiment to the letter, using the same strain of mice and the same diet. Like Ball, he observed abnormal clotting in the heart, degeneration and enlargement of the heart muscle, and early death. He also showed by electrocardiogram that the hearts of the copper-deficient mice were often contracting abnormally (arrhythmia).
But then the coup de grace: he prevented these symptoms by supplementing the drinking water of a second group of mice with copper (4). In the words of Dr. Klevay: "copper was an antidote to fat intoxication" (5). I believe this was his tongue-in-cheek way of saying that the symptoms had been misdiagnosed by Ball as due to dietary fat, when in fact they were due to a lack of copper.
Since this time, a number of papers have been published on the relationship between copper intake and cardiovascular disease in animals, including several showing that copper supplementation prevents atherosclerosis in one of the most commonly used animal models of cardiovascular disease (6, 7, 8). Copper supplementation also corrects abnormal heart enlargement-- called hypertrophic cardiomyopathy-- and heart failure due to high blood pressure in mice (9).
For more than three decades, Dr. Klevay has been a champion of the copper deficiency theory of cardiovascular disease. According to him, copper deficiency is the only single intervention that has caused the full spectrum of human cardiovascular disease in animals, including:
- Heart attacks (myocardial infarction)
- Blood clots in the coronary arteries and heart
- Fibrous atherosclerosis including smooth muscle proliferation
- Unstable blood vessel plaque
- Foam cell accumulation and fatty streaks
- Calcification of heart tissues
- Aneurysms (ruptured vessels)
- Abnormal electrocardiograms
- High cholesterol
- High blood pressure
The second reason you may not have heard of the theory is due to a lab assay called copper-mediated LDL oxidation. Researchers take LDL particles (from blood, the same ones the doctor measures as part of a cholesterol test) and expose them to a high concentration of copper in a test tube. Free copper ions are oxidants, and the researchers then measure the amount of time it takes the LDL to oxidize. I find this assay tiresome, because studies have shown that the amount of time it takes copper to oxidize LDL in a test tube doesn't predict how much oxidized LDL you'll actually find in the bloodstream of the person you took the LDL from (10, 11).
In other words, it's an assay that has little bearing on real life. But researchers like it because for some odd reason, feeding a person saturated fat causes their LDL to be oxidized more rapidly by copper in a test tube, even though that's not the case in the actual bloodstream (12). Guess which result got emphasized?
The fact that copper is such an efficient oxidant has led some researchers to propose that copper oxidizes LDL in human blood, and therefore dietary copper may contribute to heart disease (oxidized LDL is a central player in heart disease-- read more here). The problem with this theory is that there are virtually zero free copper ions in human serum. Then there's the fact that supplementing humans with copper actually reduces the susceptibility of red blood cells to oxidation (by copper in a test tube, unfortunately), which is difficult to reconcile with the idea that dietary copper increases oxidative stress in the blood (13).
The third reason you may never have heard of the theory is more problematic. Several studies have found that a higher level copper in the blood correlates with a higher risk of heart attack (14, 15). At this point, I could hang up my hat, and declare the animal experiments irrelevant to humans. But let's dig deeper.
Nutrient status is sometimes a slippery thing to measure. As it turns out, serum copper isn't a good marker of copper status. In a 4-month trial of copper depletion in humans, blood copper stayed stable, while the activity of copper-dependent enzymes in the blood declined (16). These include the important copper-dependent antioxidant, superoxide dismutase. As a side note, lysyl oxidase is another copper-dependent enzyme that cross-links the important structural proteins collagen and elastin in the artery wall, potentially explaining some of the vascular consequences of copper deficiency. Clotting factor VIII increased dramatically during copper depletion, perhaps predicting an increased tendency to clot. Even more troubling, three of the 12 women developed heart problems during the trial, which the authors felt was unusual:
We observed a significant increase over control values in the number of ventricular premature discharges (VPDs) in three women after 21, 63, and 91 d of consuming the low-copper diet; one was subsequently diagnosed as having a second-degree heart block.In another human copper restriction trial, 11 weeks of modest copper restriction coincided with heart trouble in 4 out of 23 subjects, including one heart attack (17):
In the history of conducting numerous human studies at the Beltsville Human Nutrition Research Center involving participation by 337 subjects, there had previously been no instances of any health problem related to heart function. During the 11 wk of the present study in which the copper density of the diets fed the subjects was reduced from the pretest level of 0.57 mg/ 1000 kcal to 0.36 mg/1000 kcal, 4 out of 23 subjects were diagnosed as having heart-related abnormalities.The other reason to be skeptical of the association between blood copper and heart attack risk is that inflammation increases copper in the blood (18, 19). Blood copper level correlates strongly with the marker of inflammation C-reactive protein (CRP) in humans, yet substantially increasing copper intake doesn't increase CRP (20, 21). This suggests that elevated blood copper is likely a symptom of inflammation, rather than its cause, and presents an explanation for the association between blood copper level and heart attack risk.
Only a few studies have looked at the relationship between more accurate markers of copper status and cardiovascular disease in humans. Leukocyte copper status, a marker of tissue status, is lower in people with cardiovascular disease (22, 23). People who die of heart attacks generally have less copper in their hearts than people who die of other causes, although this could be an effect rather than a cause of the heart attack (24). Overall, I find the human data lacking. I'd like to see more studies examining liver copper status in relation to cardiovascular disease, as the liver is the main storage organ for copper.
According to a 2001 study, the majority of Americans may have copper intakes below the USDA recommended daily allowance (25), many substantially so. This problem is exacerbated by the fact that copper levels in food have declined in industrial nations over the course of the 20th century, something I'll discuss in the next post.
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