"Mechanism behind omega-6 seed oil triggering autoimmune diseases"
Read the whole thing, in which linoleic-acid-derived HNE seems to create antibodies against DNA, of all things.
Welcome, Stan!
Reflections on barefoot-style running, healthy diets, and moving in the right direction.
Confirming some of Tim Noakes' work:
"When researchers later downloaded the data, the three women had peak temperatures during the race ranging from 105.4 to 106.7 degrees (40.8 to 41.5 C)—all higher than the 105 degree (40.5 C) threshold that’s considered a key diagnostic sign of exertional heat stroke. Yet they hadn’t collapsed. In fact, the team won a medal."
Read the whole thing: "How Elite Athletes Respond to Extreme Heat"
Worries about body temperature, especially in fever, are unjustified most of the time.
"I was adamant about maintaining product quality and integrity from the earliest of discussions with Kraft Heinz, and they were fully aligned with this from the beginning....
"If those ingredients change, you will stop buying. Business 101.
"I know that. Kraft Heinz knows that....
"I think of all the people dousing the salad their doctor said they should start eating in soybean oil-based dressing and buying “olive oil mayo” that was mostly just seed oil, and it frustrates me. Imagine if they switched? Imagine if they all switched? Imagine if we were able to shift the collective omega-6:omega-3 ratio back toward ancestral optimums. Longtime readers know how big a change a person can make in his or her health just by changing the fats you eat. Now imagine a population doing it."
Could be.
Fascinating post, especially the association between removal of the appendix and protection from Parkinson's.
Appendicitis was one of Burkitt's Diseases of Civilization...
The most illuminating moment I had concerning running form was when I got lost on a trail run, and had to get back in the dark.
It turned out running in the dark was easier than walking, and the fact that I couldn't see what I was stepping on in my Vibram FiveFingers made it easier, not harder.
I realized my brain was just interfering with my body, like an annoying backseat driver.
One it was forced by blindness to shut up, things went much more smoothly .
They never actually mention linoleic acid, but they do discuss lipid peroxidation and some of the products thereof, such as malondialdehyde, which are produced from LA.
"While the specific mechanisms underlying asthma have yet to be identified, there is accumulating evidence that oxidative stress from altered GSH/GSSG redox status may play an important role in the modulation and severity of the disorder."
So the molecular mechanism section is quite incomplete.
As such, it's an annoying article, as it is a missed opportunity from a mechanistic perspective, many of which have been described under other contexts. It also does not discuss the similarities to atherosclerosis, which are pretty obvious when reading this paper.
But the therapeutic approaches are sound, and validate the underlying concept of omega-6 fat involvement in asthma.
"Glutathione Redox Control of Asthma: From Molecular Mechanisms to Therapeutic Opportunities"
Hat tip to Chris Masterjohn.
"Having a low VO2max increased CVD mortality risk as much or more than traditional risk factors such as diabetes mellitus, high cholesterol levels, hyperension, or current cigarette smoking"
Wow.
"Is the Paleo Diet Right for You?"
"In the Paleo era, people ran around all day and rarely lived past 40, so their risk of developing the so-called diseases of civilization is unknown."That's not even the article, it's just the starting blurb, which ought to entice us to read further, not induce wincing, as is the case here.
"Energy expenditure and activity among Hadza hunter-gatherers." [1]
"Life expectancy is an average, and it fluctuates with age as the risks we face change throughout our lifetimes. Both those facts make it a frequently misunderstood statistic. High infant-mortality rates depress the figure substantially. This can lead contemporary observers to the false conclusion that most humans died quite young, even in the not-so-distant past."
"Skeletons from Greece and Turkey show that the average height of hunter-gatherers toward the end of the ice ages was a generous 5' 9'' for men, 5' 5'' for women. With the adoption of agriculture, height crashed, and by 3000 B. C. had reached a low of only 5' 3'' for men, 5' for women. By classical times heights were very slowly on the rise again, but modern Greeks and Turks have still not regained the average height of their distant ancestors...
"...Compared to the hunter-gatherers who preceded them, the farmers had a nearly 50 per cent increase in enamel defects indicative of malnutrition, a fourfold increase in iron-deficiency anemia (evidenced by a bone condition called porotic hyperostosis), a theefold rise in bone lesions reflecting infectious disease in general, and an increase in degenerative conditions of the spine, probably reflecting a lot of hard physical labor. "Life expectancy at birth in the pre-agricultural community was about twenty-six years," says Armelagos, "but in the post-agricultural community it was nineteen years. So these episodes of nutritional stress and infectious disease were seriously affecting their ability to survive.""I haven't even gotten out of the blurb yet, and we've discovered 81% of the words in the blurb are untrue or at least grossly questionable statements.
"There have been no studies of large groups of people who have followed the currently popular versions of the Paleo diet for decades to assess their long-term health effects."
"Several short-term studies among small groups of people (often with no control groups) suggest that the Paleo diet is more effective than the Mediterranean approach..."
"In sum, Zuk has written a wide-ranging, accessible, and stimulating book, but one that mainly triumphs in dispatching paleo-hucksters, anonymous bloggers, and scholarly straw men. In failing to acknowledge the successes of the mismatch perspective, Zuk has reached the wrong conclusion: The mismatch perspective has not been a failure; it has been tremendously fruitful."Now what you need to understand is that Dr. Zuk's book was published in 2012, and Ms. Brody's NYT article was published on August 6, 2018. So it's six years out of date.
Argh! |
@BenBikmanPhD @JimJohnsonSci
This study is my entire argument: hyperglycemia + n-6 https://t.co/eamYUsAcEE #lcl6
— Tuck (@TuckerGoodrich) March 16, 2017
"Diabetic patients are particularly susceptible to cardiomyopathy independent of vascular disease, and recent evidence implicates cell death as a contributing factor. Given its protective role against apoptosis, we hypothesized that dietary n-6 polyunsaturated fatty acid (PUFA) may well decrease the incidence of this mode of cardiac cell death after diabetes."
"...The majority of studies that have looked at the relations between lipotoxicity and cardiovascular complications of diabetes have utilized lard or other sources of saturated dietary fat rich in palmitic acid (7, 17, 26). However, in humans, increased awareness of obesity and its cardiovascular complications have led to an indiscriminate substitution of atherogenic saturated cooking fats with “heart-friendly” refined vegetable oils, such as sunflower oil, rich in n-6 polyunsaturated fatty acids (PUFA) (42). In several studies, n-6 PUFA conferred protection against arrhythmias (32) and coronary artery disease (12) and, at least in human primary fibroblasts and Leydig cells, prevented apoptosis (4, 31)."Excellent, seed oils (a more precise term than vegetable oils) are the primary source of such fats, and they're what the Dietary Guidelines suggest we eat to stave off heart disease.
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Prevalence of heart failure in 5,881 Framingham participants according to obesity status. |
"We hypothesized that, given the role of saturated fatty acids in accelerating cardiac apoptosis after diabetes, switching to an n-6 PUFA-rich diet may well be protective against cell death."They're trying to test what happens with the "indiscriminate" replacement of saturated animal fats with seed oils in diabetics, using a mouse model.
Table 1. Composition of diets |
Table 2. About the recently-deceased rats |
"...We hypothesized that dietary n-6 polyunsaturated fatty acid (PUFA) may well decrease the incidence of this mode of cardiac cell death after diabetes."Apoptosis is a process of controlled cell death, which allows the body to get rid of damaged cells before say, they become cancerous. While many in the online community get worked up about it, and pursue it through fasting, it's really just a basic house-keeping process, that probably goes on all the time. It's certainly plausible that too much apoptosis could be a bad thing, just as too much of anything could be bad. Clearly having too many heart cells (myocytes) die off could be problematic, and would explain much of heart failure.
"Recently, we demonstrated that feeding a 20% (wt/wt) palm oil diet (rich in palmitic acid) to diabetic rats enhances cardiac apoptosis in vivo..."
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Fig. 2. Apoptosis protection from n-6 PUFA |
"To verify necrosis, serum LDH [lactate dehydrogenase] was estimated using an appropriate kit (Sigma). However, release of LDH does not necessarily imply cardiac necrosis. Thus, to verify cardiac necrosis, sections were evaluated histologically using Masson’s trichrome stain..."The Bad News
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Fig. 3. Necrosis via lactate dehydrogenase |
"In these hearts, a rise in linoleic acid and depleted cardiac glutathione could explain this “switch” to necrotic cell death."But they did mention that it's not a sure-fire indicator, and so they had a visual check of heart cells as a backup method.
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Fig. 3 A. Normal heart (NC) | Fig. 3 D. Necrotic heart (PD) |
"Black arrows, severe disruption of contractile apparatus (hypercontracted muscle and thickened fibers); white arrows, focal necrosis (gray discoloration) in... PD hearts (D, 600). Cardiac necrosis was absent in NC (A, 400)..."Indeed it appears that the n-6 + diabetes rats have suffered a catastrophic onset of heart failure via necrosis. In just four days! N-6 did indeed "protect" them from apoptosis, by shifting to a worse outcome.
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Fig. 5. Cardiolipin |
"Total cardiolipin decreased almost sixfold after n-6 PUFA feeding, with a significant drop of ATP only in PD hearts, which could have contributed to cardiac necrosis (40)."
"Figure 5A depicts a mitochondrion with a double membrane and lamellar cristae, which are typical in NC, ND, and PC hearts. A novel observation in this study was abnormal condensed mitochondria, but only in the PD group (Fig. 5B)." [Image A not shown]
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Fig. 5 B. Normal mitochondria (orange), condensed (red) |
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Fig. 6 B. Glucose (white) and palmitate (black) use |
"To meet the energy demand at high afterload (135 mmHg), all except the PD group increased their glucose oxidation. With regard to fatty acid oxidation, only the NC group was able to increase palmitate oxidation, suggesting that, in the ND, PC, and PD groups, fatty acid oxidation was already operating at its maximum at low afterloads."
"A novel observation in this study was that, analogous to Barth’s syndrome, n-6 PUFA feeding for 4 wk, together with 4 days of hyperglycemia, led to similar changes in some mitochondria. Interestingly, abnormal condensed mitochondria have been recently recognized in skeletal muscle and cardiac atrial neurons from diabetic patients (25)."This is a notable finding, as excess ROS production and an inability to utilize glucose is a primary feature of Alzheimer's Disease, which is also referred to as Type III Diabetes and for which n-6-induced damage is an oft-observed possible cause.
Fig. 4 A GSH in Control (white), Diabetic (black) |
"PUFA feeding was associated with a significant decrease in GSH. Interestingly, diabetes for 4 days in normal chow-fed rat hearts could not decrease cardiac GSH, whereas superimposition of diabetes in PUFA-fed animals led to a further decrease in cardiac GSH levels (Fig. 4A)"
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Fig. 8. Heart function |
"At higher afterloads, glucose and fatty acid oxidation increased in the NC group. In ND and PC hearts, the only increase was that of glucose oxidation, inasmuch as, presumably, fatty acid oxidation was already operating at its maximum. The PD group alone failed to increase its glucose oxidation in response to a higher energy demand, an aspect that could have contributed to the drop in cardiac function."
"In our study, n-6 PUFA feeding substantially increased cardiac fatty acid in the PC and PD groups, but only PD hearts demonstrated a considerable increase in lipid droplets."
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Rat weight at STZ injection. Red indicates weight lost after injection (4 days) |
"Interestingly, in contrast to the ND group (361 ± 9 and 358 ± 9 g before and after STZ, respectively), diabetes in PUFA-fed animals was associated with a profound loss of body weight (450 ± 11 and 393 ± 11 g before and after STZ, respectively). This loss in body weight could not be attributed to any change in food or fluid intake but could be a result of excessive lipolysis and loss of adipose tissue mass with subsequent increases in serum free fatty acids and TG in the PD group."
"Thus, although promoted as being beneficial, excess n-6 PUFA, with its predisposition to induce obesity, insulin resistance, and ultimately diabetes, could accelerate myocardial abnormalities in diabetic patients... Circulating TG were higher in the PC than in the NC group, and serum insulin was increased in the PC group (likely as a consequence of insulin resistance) compared with the NC group, but there was no overt hyperglycemia in the PC group."
Table 2. PC is PUFA Control, not the intervention! |
"In rodents fed high-fat diets, insulin resistance does not progress to hyperglycemia in the absence of genetic defects (36)."So these rats seem to have gotten as close to Type 2 diabetes as it's possible for them to have gotten.
"In summary, chronic caloric excess of n-6 PUFA when coupled with acute diabetes of only 4 days precipitated mitochondrial abnormalities, a steep drop in GSH, altered substrate utilization, and myocardial TG deposition. Given that these hearts also demonstrated necrosis and extensive myocardial cell loss, a feature that is predominant only in chronic diabetes (1, 14, 16, 24), our data suggest that this mode of cell death in PUFA-fed diabetic hearts is an important factor in accelerating diabetic cardiomyopathy. Although these effects of n-6 PUFA in the diabetic animal would seem contrary to accepted belief as being beneficial, in countries such as Israel, with high dietary n-6 PUFA consumption, there is an excessive incidence of obesity, insulin resistance, hypertension, and type 2 diabetes (6).... Thus advocating diets rich in n-6 PUFA for diabetic patients could accelerate the impairment of myocardial contractility."This also is the only study I know of that shows the effects of hyperglycemia to significantly accelerate the negative effects of n-6 PUFA feeding on an organism. The PC and PD groups can be seen as a model for the progression of obesity and insulin/leptin resistance to an advanced form of chronic Type 2 with advanced pancreatic beta-cell death, a condition that is becoming increasingly common in human children.
"However, in humans, increased awareness of obesity and its cardiovascular complications have led to an indiscriminate substitution of atherogenic saturated cooking fats with “heart-friendly” refined vegetable oils, such as sunflower oil, rich in n-6 polyunsaturated fatty acids (PUFA) (42)."Good for them!)
From Grace Under Pressure
"Five Tips to Surviving Foundation Japanese"
My daughter got a job writing for the school website. This is her first post.
Read the whole thing!
"However, the ability of adipose tissue to expend energy is a dynamic process that continues to increase with prolonged cold exposure, only reaching maximal capacity after several weeks (Cannon and Nedergaard, 2004)."And clearly staying warm is overwhelmingly dependent on fat metabolism.
"However, the enrichment of lipid metabolism proteins far eclipsed that of proteins involved in all other metabolite pathways from 3 days to 3 weeks of cold exposure (Figure 1B)."This likely explains why overweight people or inactive people have such a problem staying warm. Fat-burning capacity is dependent on stimulus, and while this doesn't show it, it likely atrophies like every other function of the body. Use it or lose it.
"Newly synthesized CL is characterized by shorter, more saturated acyl chains, which can be remodeled by phospholipases, and acyltransferases through monolysocardiolipin (monolysoCL) intermediates to generate a diverse pool of CLs."It shouldn't surprise that CL is produced in an ideal state. Why it so readily takes up linoleic acid is an interesting question...
Fat components |
"The DELTA Investigators express thanks to the following contributors: AARHUS, Bertolli, USA., Best Foods, Campbell Soup Company, Del Monte Foods, General Mills, Hershey Foods Corp., Institute of Edible Oils and Shortenings, Kraft General Foods, Land O'Lakes, McCormick Incorporated, Nabisco Foods Group, Neomonde Baking Company, Palm Oil Research Institute, Park Corporation, Procter & Gamble, Quaker Oats, Ross Products Division/Abbott Laboratories, Swift-Armour and Eckrick, Van Den Bergh Foods, Cholestech, Lifelines Technology Incorporated."Wow.
"Convincing evidence suggests that oxidative modification of LDL plays an important role in the pathophysiology of atherogenesis (Steinberg 1997). In recent years, numerous molecular mechanisms have been proposed to explain the different oxidation pathways that lead to modification of LDL (Steinberg 1997).
"One of the earliest steps in the generation of oxidatively modified LDL is the peroxidation of its polyunsaturated fatty acids (PUFA).3 The oxidative breakdown products of these fatty acids, such as malondialdehyde [MDA] and 4-hydroxynonenal [HNE], form covalent bonds with apolipoprotein B (apo B)..."
"The results of the present study also show that LDL composition (LDL quality) affects susceptibility to oxidation. [It] was inversely correlated with the quantity of LDL oleic acid (r = −0.29, P < 0.01), and positively correlated with the quantity of LDL linoleic acid (r = 0.23, P = 0.04) and the 18:2-to-18:1 ratio (r = 0.52, P < 0.001). The oxidation rate was positively correlated with the 18:2-to-18:1 ratio (r = 0.24, P = 0.03)."
"In the present study, the ratios of 18:2 to 18:1 and PUFA to MUFA in the LDL from subjects when they consumed the Step-1 and Low-Sat diets were significantly lower than they were in the LDL from subjects when they consumed the AAD. Linoleic acid (n-6) in LDL from subjects when they consumed the Low-Sat diet also was significantly lower compared with those from subjects when they consumed the AAD. "
"LDL oxidized faster after the linoleate diet than after the oleate diet... and produced more conjugated diene [that's bad] in proportion to the increase in LDL linoleate."Here's where we get to the shaking my head part.
"N-6 converts to these toxins? You're proved that? Why not reduce the n-6?"Let's not get too into conspiracies here, but on the face of it this study is clearly little more than a misleading advertisement for the sponsors listed above, who are forced to follow the United States Dietary Guidelines and replace saturated fats with the n-6 fat that their own research claims is harmful.
I unblocked you and looked at your study. Declining oxidation in LDL tracks w/ declining n-6 LA content in LDL, while SFA flat and MUFA went up.— Tucker Goodrich (@TuckerGoodrich) April 26, 2018
Interactions between FA is a fascinating topic, & may be due to CHO, but reinforces n-6 claim for LDL.
Figure things out, you said? pic.twitter.com/qSCu2qDkSF
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I'm the one with the bunny ears. |
Had an excellent chat with @TuckerGoodrich— Low Carb Dr. T (@TroKalayjian) April 26, 2018
Talked about gluconeogensis, seed oils, chronic biochemical stress, dose response of exercise and so much more... dude is smart!
Still got him with the bunny ears😜https://t.co/h6oLqwe3Ys pic.twitter.com/wkBT7DorPK
Some nutritionist online told me that the #Keto diet is only good for losing water weight— Low Carb Dr. T (@TroKalayjian) April 8, 2018
I am so glad that I lost 145lbs of water in these past 2 years...
🤔#Ketogenic #lowcarb #lchf #jerf pic.twitter.com/1ZIT6pYYkD
"Abstract: In the past, attempts have been made to estimate the carbohydrate contents of preagricultural human diets. Those estimations have primarily been based on interpretations of ethnographic data of modern hunter-gatherers. In this study, it was hypothesized that diets of modern hunter-gatherers vary in their carbohydrate content depending on ecoenvironments."Diets of modern hunter-gatherers vary substantially in their carbohydrate content depending on ecoenvironments: results from an ethnographic analysis"
"Thus, using data of plant-to-animal subsistence ratios, we calculated the carbohydrate intake (percentage of the total energy) in 229 hunter-gatherer diets throughout the world and determined how differences in ecological environments altered carbohydrate intake. We found a wide range of carbohydrate intake (≈3%-50% of the total energy intake; median and mode, 16%-22% of the total energy). Hunter-gatherer diets were characterized by an identical carbohydrate intake (30%-35% of the total energy) over a wide range of latitude intervals (11°-40° north or south of the equator).
"However, with increasing latitude intervals from 41° to greater than 60°, carbohydrate intake decreased markedly from approximately equal to 20% to 9% or less of the total energy. Hunter-gatherers living in desert and tropical grasslands consumed the most carbohydrates (≈29%-34% of the total energy). Diets of hunter-gatherers living in northern areas (tundra and northern coniferous forest) contained a very low carbohydrate content (≤15% of the total energy).
"In conclusion, diets of hunter-gatherers showed substantial variation in their carbohydrate content. Independent of the local environment, however, the range of energy intake from carbohydrates in the diets of most hunter-gatherer societies was markedly different (lower) from the amounts currently recommended for healthy humans."
"Marathon-ready Daniel Lieberman offers evolutionary perspective on Bannister 4-minute mile, human speed limits, and ‘Man Against Horse’".
"...He did talk about the kinds of shoes that he wore back in the day, and was fascinated by — and not particularly approving of — how running shoes had gotten so built up. He, like any fast miler, was a forefoot striker. We published a few years later the paper in which we made the argument that, essentially, prior to shoes pretty much everybody ran the way Bannister ran. He felt that was clearly the best way to run.
"I remember him describing how he had his shoes made by a cobbler in London. You couldn’t go to a shoe store back then and buy a pair of running shoes. He basically had to have his shoes custom made. I remember he discussed how hard it was to get the right kind of material — light but durable enough not to fall apart...."
Interesting list, with people like Magness, Dicharry, and Lieberman:
“I wear a variety of different shoes to mix it up, but all are zero drop, because I’m a forefoot striker and don’t need or want any cushioning on the heel, otherwise I end up running like a ballerina”...
Apparently a must-read paper, according to the interviewer of one of the authors:
"Do Traditional People Hold the Key to a Healthy Life? 15 Questions with Researcher Pedro Carrera Bastos"
Don't know how I missed this. The other authors: Maelan Fontes-Villalba, James H O’Keefe, Staffan Lindeberg, Loren Cordain.
"Regarding dietary changes, it should be mentioned
that, in the US, dairy products, cereal grains (especially the
refined form), refined sugars, refined vegetable oils, and
alcohol make up to 70% of the total daily energy consumed."
What's the excretion pathway for iron?— Tucker Goodrich (@TuckerGoodrich) November 26, 2017
Minor losses through skin, blood, and sweat.— P. D. Mangan 🇺🇸🏴🇮🇪 (@Mangan150) November 26, 2017
Iron retention per year |
"On the basis of turnover rates, these subjects needed to replace as little as 2% and as much as 95% of their body iron annually!"They used radioactive iron to measure iron turnover, which was the same method used as Green. Seems a reasonable way to do it.
"Current US dietary recommendations for iron use the body weights and the daily iron losses of the subjects of Green et al (2) to derive an average estimated iron loss of 14 µg/kg...."
"This reduction, together with the tendency in the present study for the men to (nonsignificantly) increase their body iron in 3 y may mean that dietary recommendations for men in Western countries may best focus on preventing body iron accumulation rather than iron deficiency."
"Green et al... measured basal iron losses of 0.95 ± 0.30 mg/d for white men in the United States, 0.90 ± 0.31 mg/d for Mestizo men in Venezuela. and 1.02 ± 0.22 mg/d for Indian men in South Africa. Higher and more variable losses of 2.42 ± 1.09 and 2.01 ± 0.94 mg/d for Bantu men in Johannesburg and Durban, South Africa, respectively, were attributed to greater than normal body iron stores in the Bantu population."
"Among the South African Bantu, the intake of iron is often very high—as much as 200 mg. per diem. This high intake is due mainly to the uptake of the element from iron utensils occuring during the preparation of their usual foods (particularly fermented cereal products)."Dang, that's 100-fold what Green reported them losing per day! They must be like Tetsuo, The Iron Man!
"...there appears to be no evidence that iron overload per se is detrimental to well-being."If the Bantu are eating that much iron and seeing no ill effects, then I think we in the West can worry less about it.
"Researchers originally believed that the popular, iron-rich beer caused cases of African iron overload. However, many individuals that drank the beer did not develop the disorder and some individuals that did not drink the beer did develop it. This led researchers to speculate that a mutation of a gene or genes involved in the transport or breakdown (metabolism) of iron must play a role in the development of African iron overload. Such a gene has not yet been identified."That's from the Rare Diseases site, 2013. So it's similar to the iron overload disease that most are familiar with, hemochromatosis.
"Despite this substantial range in iron excretion, homeostatic control mechanisms were effective at maintaining body iron homeostasis for most subjects, with substantially impaired iron-status indexes in only one menstruating woman... These considerable differences in iron excretion and resulting requirements can generally be appropriately met by physiologic control of iron absorption, provided that dietary iron is accessible and reasonably bioavailahle."Iron, like most important things, is tightly, homeostatically regulated by the body. As a creature that appears to have evolved on a diet of large amounts of heme-rich ruminant meat, we are unlikely to be susceptible to iron poisoning via that route, that is, via a diet far higher in heme iron than what most humans alive today eat. So unless you have an actual genetic problem, it's not necessary to manually regulate things like air, water, or your body's iron stores.