I wanted to write this post to summarize my current understanding of mineral balancing hay in the Equine diet. This is a rather complex topic and I make no claim for my post to be complete or even up to the newest standards of research. The topic itself is not very close to my heart, as I personally have never seen any effect of "iron overload" and so I did not dive too deep in this matter, yet thought it was important for me to gain a "common sense" understanding that would be consistent with my background in Biology.
The background on the whole topic is provided briefly here. In brief, there seems to be some indication that elevated ferritin levels in the horse's blood (as a proxy for the amount of iron stored in the horse's body) could be a risk factor to develop insulin resistance and laminitis in horses. High serum ferritin is suggested to stem from hay rich in iron, or well water rich in iron, or other feeds with supplemental iron or naturally high iron content.
The one fact that is easy to confirm for anybody trying to is that some hays and some well water are very high in iron. Some! Not all. My own hay for example, tested during three consecutive years was normal to low in iron, and consistent through the years with respect to iron content. I also must point out that just the appearance of redish stain in well water, tubs and toilets does not mean that the water is high in iron, it could also be high in tannins, which has the same color, but a completely opposite effect on the horse. So a water analysis is necessarily required to determine if redish stained water is from tannins or iron.
Even hays that have normal iron content do pretty much always meet the minimum requirements for iron for horses, as published by the National Research Council. So definitely, there is no shortage of iron in an average horse's diet. Unfortunately, this is were the simplicity of the topic ends.
Before I will go into detail on how some believe it is possible to counteract the high iron content and high ferritin levels in horses by "mineral balancing" the horses ration, I will have a closer look at the evidence for the correlation between ferritin level and blood insulin response, based on the above mentioned paper, that was published in February of this year.
The study analyzed 16 horses of various ages and sex. 15 horses were healthy and one horse had a diagnosed insulin resistance. The authors analyzed the data for all 16 horses in the same statistical test. As I show below, this is not very good practice as an outlier "drives" correlations. To show what I mean I took the raw data from the paper and produced 2 figures in Excel, the top excluding the IR mare from the analysis and the bottom including it. Both datasets show a positive correlation, but only the bottom one is significant (P < 0.05). Among the healthy horses (top panel) the two with the highest ferritin concentration showed a very low insulin response.
Thus, among healthy horses, we cannot establish a link between ferritin level and strength of insulin response at this point in time.
The IR mare had the highest ferritin levels of all horses and the strongest insulin response. The point is labeled in orange at the bottom plot. Including this one horse thus "drives" the correlation into significance. But it is rather meaningless, as first, we cannot know if the IR mare exhibits high ferritin as a cause or consequence of the insulin resistance (i.e. no causal relationship can be established from a simple correlation) and second, as the healthy horses showed no significant correlation, we cannot use ferritin levels as predictor for insulin response. In short, it is not totally clear to me why we should care about ferritin levels and iron overload in the healthy horse in the first place?
However, if we accept for the moment that there IS a causal relationship between insulin resistance and "iron overload", we can ask if there is any way to reduce the effect of the high dietary iron and thus help the insulin resistant horse. According to Dr. Kellon, there is, by a practice called mineral balancing of hay. The best way to learn about that practice is by reading this website, other than taking the course offered by Dr. Kellon.
The basics of the method are easily understood. It requires the horse owner to obtain the nutritional content of their hay by getting it analyzed in a laboratory, which will determine the amounts of macro and microminerals per pound of hay. Multiplied by the amount of hay eaten by the horse we know exactly how much of each mineral a horse is getting through its forage diet. These values then can be compared to the minimal requirements for each nutrient as established by the National Research Council. If any nutrient is deficient, we can supplement it. The emphasis here is on IF a nutrient is deficient, we can supplement it. This is the major contribution by Dr. Kellon that I am personally very thankful for, because she pointed out that many horses don't need a lot of supplementation, if their forage already contains adequate levels of nutrients. On the other hand, many hays also suffer from notorously low content of some minerals, most commonly copper and zinc. So bottom line is, in order to "balance" the hay diet, we only need to provide what is actually missing.
Now comes the confusing part, at least for me. And this concerns the question how much do we actually need to provide in order to make up for deficiencies in our hay. Since most hays provide an over-abundance of iron, and a deficiency of copper and zinc, Dr. Kellon recommends to not only supplement copper and zinc deficiencies to the amount of the minimal daily requirements (or a little above), but to provide them in a vast excess in order to counteract the excess of iron. The rationale here is that iron and zinc are supposed to compete for absorption in the intestinal wall. With a large excess of iron, zinc basically is out-competed from binding at the receptor that would transport the mineral across the intestinal wall into the blood stream. If we artificially lift the zinc concentration we allow it to better compete against iron for absorption.
In my understanding there are two problems with this practice of providing zinc and copper in over-abundance to counteract the effects of iron. My view stems from reading this paper. The paper can be downloaded for free here. Below is my brief summary and a little of my own research, which is basically limited to zinc. I have not had the time to look in more detail into copper absorption.
While there is evidence that iron inhibits zinc absorption, the reverse does not seem to be true. It almost certainly does not happen at the level of the receptor, the "divalent metal transporter-1" (DMT1) protein. DMT1 was historically thought to transport both Zi and Fe (iron) through the enterocyte (the "gut cell") to the blood, but does now seem to only transport Fe, but not Zi. In humans, a family of specific zinc transporters has been identified. The genes that encode those proteins are called hZip1, hZip2 and hZip4, etc. hZip1 for example is specific for regulating zinc homeostasis in the human gut cell. Given that zinc seems to have its own absorption mechanism it seems very unlikely that the negative interaction between iron and zinc happens at the level of "competing for absorption" in the intestine.
The orthologues gene of hZip1 is also present in the horse, its name and genomic location can be viewed here. Those who are fascinated by evolution, can also see that those zinc transporters have been highly conserved through vertebrate evolution, suggesting that the mechanism of regulating zinc homeostatis could likely be conserved too. In total I found 113 genes involved in zinc transport organized in 12 protein families in the horse. I think this speaks very clearly for a much more complex (and so far unknown) picture than a direct competition of iron and zinc for absorption in the intestinal wall. Or in simple words, iron will be absorbed no matter how much zinc we feed to the horse, as both metals have their own specific transport mechanisms and do not compete for absorption by using the same transporter.
It is also worthwhile mentioning that almost all biological system have built-in "feedback loops". In the case of iron absorption, for example, it was shown (in cell cultured gut cells) that the iron transporter gene dmt1 is down-regulated in the presence of high iron in the medium. This effectively reduces the amount of possible iron absorbed, since simply less transporter molecules will be available to absorb iron, when iron is present in excess in the horses body.
The second aspect of confusion deals with how oversupplementation with zinc could offset iron absorption, given the anatomy of the digestive tract. Most mineral absorption happens in the small intestine, where the food passes through within 90 minutes. If we supplement large amounts of zinc in a single feeding, this large quantity of zinc is basically available to "buffer" iron only for that (short) amount of time, assuming that zinc and iron do compete for absorption (which is unlikely given the paragraph above). During the remaining >22 h there is no excess zinc in the horses digestive system (assuming any zinc not absorbed by the small intestine moves along to the large intestine with the rest of the digest) and thus is unlikely to help with reducing Fe absorption of the hay that is eaten after the supplement has left the small intestine. Moreover, there may simply not be enough receptors in the intestinal wall to absorb such a large amount of supplemental zinc, if, for example, it is provided at 10 times the minimum daily requirements in a single feeding.
In 2006 Dr. Kellon reported findings comparing IR horses on a "mineral-balanced" diet to IR horses on an "unbalanced" diet. The details of the study can be downloaded here. The mineral balanced diet consisted of one that overcompensated for the supposed effect of iron, i.e. copper and zinc were fed in excess of minimal daily requirements. She found significant differences in blood iron status between those two treatment groups and therefore suggests that mineral balancing the diet could lower the iron status of the horse. The problem with this study, as is also acknowledge by her in the paper, is that the two treatment groups are "confounded", meaning that not only differed the treatments in mineral intake, but also in the fact that the mineral balanced group of horses received forage with low NSC while the horses in the unbalanced diet group did not. So instead of attributing the lower iron status to mineral intake, it could just as well be attributed to the lower NSC of the forage. In fact, I personally would find this a much more realistic explanation, but without a controlled study we don't know anything for sure. Such a controlled study would need to have 4 treatment groups, and not only two: one on low NSC forage plus balanced minerals, one on low NSC forage without balanced minerals and one on high NSC forage without balanced minerals and one on high NSC forage with balanced minerals. And ideally even one group of horses receiving low NSC forage and minerals only at the minimum daily requirements, without overcompensation for the supposed effect of iron. To my knowledge such a study to this point does not exist. However, even if such a study would exist, it would still be impossible to say that iron overload caused insulin resistance in horses. I think it is rather clear that insulin resistant horses do have high body content of iron, but the causal link is almost impossible to establish. A correlation does never imply causality. It could just as well be that IR horses also have problems with iron homeostatis, but that those two effects are totally unlinked.
My current feeling with mineral balancing is that it is a great way to supplement specifically what is missing in a horses diet, and only that, thus not overloading our horses with components they actually don't need. But also that some of the specifics of the practice is questionable, especially when it comes to counteract the excess iron due to fear of iron overload. To me it is not clear that counteracting one excess (iron) with another (zinc) is the right cause of action, especially considering the fact that there is only limited evidence that iron overload is causally related to insulin resistance in horses and that zinc seems ineffective in limiting iron absorption.
The background on the whole topic is provided briefly here. In brief, there seems to be some indication that elevated ferritin levels in the horse's blood (as a proxy for the amount of iron stored in the horse's body) could be a risk factor to develop insulin resistance and laminitis in horses. High serum ferritin is suggested to stem from hay rich in iron, or well water rich in iron, or other feeds with supplemental iron or naturally high iron content.
The one fact that is easy to confirm for anybody trying to is that some hays and some well water are very high in iron. Some! Not all. My own hay for example, tested during three consecutive years was normal to low in iron, and consistent through the years with respect to iron content. I also must point out that just the appearance of redish stain in well water, tubs and toilets does not mean that the water is high in iron, it could also be high in tannins, which has the same color, but a completely opposite effect on the horse. So a water analysis is necessarily required to determine if redish stained water is from tannins or iron.
Even hays that have normal iron content do pretty much always meet the minimum requirements for iron for horses, as published by the National Research Council. So definitely, there is no shortage of iron in an average horse's diet. Unfortunately, this is were the simplicity of the topic ends.
Before I will go into detail on how some believe it is possible to counteract the high iron content and high ferritin levels in horses by "mineral balancing" the horses ration, I will have a closer look at the evidence for the correlation between ferritin level and blood insulin response, based on the above mentioned paper, that was published in February of this year.
The study analyzed 16 horses of various ages and sex. 15 horses were healthy and one horse had a diagnosed insulin resistance. The authors analyzed the data for all 16 horses in the same statistical test. As I show below, this is not very good practice as an outlier "drives" correlations. To show what I mean I took the raw data from the paper and produced 2 figures in Excel, the top excluding the IR mare from the analysis and the bottom including it. Both datasets show a positive correlation, but only the bottom one is significant (P < 0.05). Among the healthy horses (top panel) the two with the highest ferritin concentration showed a very low insulin response.
Thus, among healthy horses, we cannot establish a link between ferritin level and strength of insulin response at this point in time.
The IR mare had the highest ferritin levels of all horses and the strongest insulin response. The point is labeled in orange at the bottom plot. Including this one horse thus "drives" the correlation into significance. But it is rather meaningless, as first, we cannot know if the IR mare exhibits high ferritin as a cause or consequence of the insulin resistance (i.e. no causal relationship can be established from a simple correlation) and second, as the healthy horses showed no significant correlation, we cannot use ferritin levels as predictor for insulin response. In short, it is not totally clear to me why we should care about ferritin levels and iron overload in the healthy horse in the first place?
The basics of the method are easily understood. It requires the horse owner to obtain the nutritional content of their hay by getting it analyzed in a laboratory, which will determine the amounts of macro and microminerals per pound of hay. Multiplied by the amount of hay eaten by the horse we know exactly how much of each mineral a horse is getting through its forage diet. These values then can be compared to the minimal requirements for each nutrient as established by the National Research Council. If any nutrient is deficient, we can supplement it. The emphasis here is on IF a nutrient is deficient, we can supplement it. This is the major contribution by Dr. Kellon that I am personally very thankful for, because she pointed out that many horses don't need a lot of supplementation, if their forage already contains adequate levels of nutrients. On the other hand, many hays also suffer from notorously low content of some minerals, most commonly copper and zinc. So bottom line is, in order to "balance" the hay diet, we only need to provide what is actually missing.
Now comes the confusing part, at least for me. And this concerns the question how much do we actually need to provide in order to make up for deficiencies in our hay. Since most hays provide an over-abundance of iron, and a deficiency of copper and zinc, Dr. Kellon recommends to not only supplement copper and zinc deficiencies to the amount of the minimal daily requirements (or a little above), but to provide them in a vast excess in order to counteract the excess of iron. The rationale here is that iron and zinc are supposed to compete for absorption in the intestinal wall. With a large excess of iron, zinc basically is out-competed from binding at the receptor that would transport the mineral across the intestinal wall into the blood stream. If we artificially lift the zinc concentration we allow it to better compete against iron for absorption.
In my understanding there are two problems with this practice of providing zinc and copper in over-abundance to counteract the effects of iron. My view stems from reading this paper. The paper can be downloaded for free here. Below is my brief summary and a little of my own research, which is basically limited to zinc. I have not had the time to look in more detail into copper absorption.
While there is evidence that iron inhibits zinc absorption, the reverse does not seem to be true. It almost certainly does not happen at the level of the receptor, the "divalent metal transporter-1" (DMT1) protein. DMT1 was historically thought to transport both Zi and Fe (iron) through the enterocyte (the "gut cell") to the blood, but does now seem to only transport Fe, but not Zi. In humans, a family of specific zinc transporters has been identified. The genes that encode those proteins are called hZip1, hZip2 and hZip4, etc. hZip1 for example is specific for regulating zinc homeostasis in the human gut cell. Given that zinc seems to have its own absorption mechanism it seems very unlikely that the negative interaction between iron and zinc happens at the level of "competing for absorption" in the intestine.
The orthologues gene of hZip1 is also present in the horse, its name and genomic location can be viewed here. Those who are fascinated by evolution, can also see that those zinc transporters have been highly conserved through vertebrate evolution, suggesting that the mechanism of regulating zinc homeostatis could likely be conserved too. In total I found 113 genes involved in zinc transport organized in 12 protein families in the horse. I think this speaks very clearly for a much more complex (and so far unknown) picture than a direct competition of iron and zinc for absorption in the intestinal wall. Or in simple words, iron will be absorbed no matter how much zinc we feed to the horse, as both metals have their own specific transport mechanisms and do not compete for absorption by using the same transporter.
It is also worthwhile mentioning that almost all biological system have built-in "feedback loops". In the case of iron absorption, for example, it was shown (in cell cultured gut cells) that the iron transporter gene dmt1 is down-regulated in the presence of high iron in the medium. This effectively reduces the amount of possible iron absorbed, since simply less transporter molecules will be available to absorb iron, when iron is present in excess in the horses body.
The second aspect of confusion deals with how oversupplementation with zinc could offset iron absorption, given the anatomy of the digestive tract. Most mineral absorption happens in the small intestine, where the food passes through within 90 minutes. If we supplement large amounts of zinc in a single feeding, this large quantity of zinc is basically available to "buffer" iron only for that (short) amount of time, assuming that zinc and iron do compete for absorption (which is unlikely given the paragraph above). During the remaining >22 h there is no excess zinc in the horses digestive system (assuming any zinc not absorbed by the small intestine moves along to the large intestine with the rest of the digest) and thus is unlikely to help with reducing Fe absorption of the hay that is eaten after the supplement has left the small intestine. Moreover, there may simply not be enough receptors in the intestinal wall to absorb such a large amount of supplemental zinc, if, for example, it is provided at 10 times the minimum daily requirements in a single feeding.
In 2006 Dr. Kellon reported findings comparing IR horses on a "mineral-balanced" diet to IR horses on an "unbalanced" diet. The details of the study can be downloaded here. The mineral balanced diet consisted of one that overcompensated for the supposed effect of iron, i.e. copper and zinc were fed in excess of minimal daily requirements. She found significant differences in blood iron status between those two treatment groups and therefore suggests that mineral balancing the diet could lower the iron status of the horse. The problem with this study, as is also acknowledge by her in the paper, is that the two treatment groups are "confounded", meaning that not only differed the treatments in mineral intake, but also in the fact that the mineral balanced group of horses received forage with low NSC while the horses in the unbalanced diet group did not. So instead of attributing the lower iron status to mineral intake, it could just as well be attributed to the lower NSC of the forage. In fact, I personally would find this a much more realistic explanation, but without a controlled study we don't know anything for sure. Such a controlled study would need to have 4 treatment groups, and not only two: one on low NSC forage plus balanced minerals, one on low NSC forage without balanced minerals and one on high NSC forage without balanced minerals and one on high NSC forage with balanced minerals. And ideally even one group of horses receiving low NSC forage and minerals only at the minimum daily requirements, without overcompensation for the supposed effect of iron. To my knowledge such a study to this point does not exist. However, even if such a study would exist, it would still be impossible to say that iron overload caused insulin resistance in horses. I think it is rather clear that insulin resistant horses do have high body content of iron, but the causal link is almost impossible to establish. A correlation does never imply causality. It could just as well be that IR horses also have problems with iron homeostatis, but that those two effects are totally unlinked.
My current feeling with mineral balancing is that it is a great way to supplement specifically what is missing in a horses diet, and only that, thus not overloading our horses with components they actually don't need. But also that some of the specifics of the practice is questionable, especially when it comes to counteract the excess iron due to fear of iron overload. To me it is not clear that counteracting one excess (iron) with another (zinc) is the right cause of action, especially considering the fact that there is only limited evidence that iron overload is causally related to insulin resistance in horses and that zinc seems ineffective in limiting iron absorption.
