Andrew - promised a follow up after I had a chance to talk with some of our scientists! I just got back from the Sea Otter Classic, so I apologize for the delay! Thank you again for the great feedback!
Re: Evidence of Nitrates increasing nitric oxide production
We have no objection to findings reporting the beneficial effect of dietary nitrates on sport activities. The mechanism behind their potency has also been described and is rather specific for this class of compounds. Objectively, it needs to be also addressed that there are publications reporting that nitrates have limited or no effect on exercise (1-4). As described, nitrates were bioavailable but did not deliver efficacious effect. Addressing all the factors involved in these unexpected results may help understand reasons of limited efficacy of ingested nitrate products. We will be soon be releasing some further study results address some unexpected information and betalains vs. dietary nitrates.
Re: Plasma Bioavailabilty Study you referenced (https://www.ncbi.nlm.nih.gov/pubmed/26873098)
This manuscript refers to the Plasma bioavailability of nitrate from Beta vulgaris. Here the authors describe how beetroot juice provides NO in high concentration but betanin was barely detected in plasma regardless of its presence in supplemented material.
However, there are other studies showing that betalains are bioavailable after ingestion (for example from cactus pear or purified betalains as such). This suggests that bioavailability of betalains may depend on other factors, such as food matrix or on co-presence of other entities to some extent (for example sugars or even nitrates). Indeed, cactus pears contain relatively lower amount of sugars compared to beets. Also, cactus pears do not contain a significant amount of nitrates. Absence of nitrates and lower amount of glucose could be one of reasons why betalains from this material are bioavailable.
Furthermore, research on the mechanism of absorption of betalains has shown the involvement of membrane transporters and receptors such as MCT1, OATP2B1, MRP2 (5). Interestingly, various components including food elements may affect functioning of these receptors and carriers resulting in reduced or enhanced absorption of betalains (6).
Therefore, results reported in the publication cited by you do illustrate negative effect of red beet matrix on bioavailability of betalains present in that material. Your observations are valid and well-founded and we would like to mention that we are already addressing this issue in scientific detail. In order to understand how our AltRed works,, we are investigating the bioavailability of betalains from our extract (12.5mg of betalains per 50mg dose) comparing it to the equivalent amount of betalains in red beet juice, following a cross-over clinical study model that we will publish. Study subjects will be receiving either our extract or red beet juice after a washout period.
So far, results from clinical trials seem to indicate that betalains from our product are highly bioavailable and that our product significantly increased sport performance in supplemented subjects. We would like to mention that the mechanism of action that involves the bioavailability of the components of our product will be quite different from the mechanism pertaining nitrates or other supplements for sport performance. We are focusing on betalain-specific mechanisms improving sport performance activities completely independent of nitrates.
In the manuscript you mentioned, there are a couple of factors that were not taken into consideration. The first, the analysis was only performed in EDTA-plasma, under the assumption that betalains would be circulating in blood as free molecules. The second, when there is an excess of betalains, these tend to be eliminated through urine and there were no determinations of betalain content reported in this study. Additionally, only betanin was determined in plasma samples. It is well documented that betanin is one of the most abundant betalains in beetroot, however, bioavailability of other betalains present in beet was not measured.
It is mentioned here since rate of absorption of different betalains seems to be different. We would like to mention that we are studying the bioavailability of betalains from our extract and our preliminary results are similar to results previously reported by research group investigating bioavailability of betalains from cactus pear. Our preliminary results show that betalains from our product are highly bioavailable within 90 minutes after ingestion (manuscript in preparation). Our next step is to describe the kinetics and efficiency of betalain absorption and how it can be correlated with improvement of sport performance.
RE: The question I posed about whether it might be the betalains and not the nitrates that are producing these performance benefits
We have determined the amount of betalains available in our product. We also know that these betalains are bioavailable since we have previously seen results about bioavailability of betalains from different sources. Therefore, we focused on efficacy first. To this date, four studies have been completed by three different research groups (3 published, one in review) showing that there is a beneficial effect on exercise performance. In two separate studies, subjects were preloaded with our product with one last dose 1.5 hours before exercise. Results of these studies show statistically positive effect (power output, speed, distance). Furthermore, we also saw the increase in exercise performance in sedentary subjects after a single dose. All these studies were double blind, and placebo controlled.
As previously mentioned the mechanism of action of betalains on sport performance is quite different compared to other sport products including nitrates and requires more discovery clinical research. We are pursuing such research and results of this work that will be submitted for publication in 2018.
Our research is focused on betalain-specific effect on sport performance. Following this path, we assume that red beets contain two very different classes of chemical entities affecting sport performance; nitrates and betalains. According to our hypothesis, bioavailablity of betalains in presence of nitrates and/or sugars in high concentration is highly inhibited. Therefore bioavailability of betalains as well as stimulatory effect of betalains on sport performance needs to be investigated in absence of nitrates.
Re: Your study about the profile content of Betalains in Plasm (https://www.ncbi.nlm.nih.gov/pubmed/29638119)
This paper is indeed interesting. Results published are raising an interesting question – how much betalain in blood is needed to provide beneficial effect on exercise. Preliminary results show that nM range is sufficient but more research is needed to conclude and to publish. Another question could be whether study subjects involved in this study could have any positive effect on sport performance if asked to exercise. Based on our observations while performing clinical studies as published – they could. The effect of Betalain is showing to be exercise induced and we will continue to publish on this.
Furthermore, people who are reporting beeturia after eating red beets (or drinking beetroot juice) do not have beeturia after taking our product. Such an observation may lead to possibility that other components not present in beets are determining whether ingestion of betalains in large quantities may result in beeturia. Based on published results, metabolism of iron may play crucial role in developing symptoms of beeturia (2 references are attached)
Again, thanks for the discussion! Would love to discuss further over the phone or next time our team is in your area! Here's a list of the references used above
(1) No improvement in endurance performance after a single dose of beetroot juice.
(2) Influence of acute dietary nitrate supplementation on 50 mile time trial performance in well-trained cyclists.
(3) Dietary nitrate does not enhance running performance in elite cross-country skiers.
(4) Sodium nitrate supplementation does not enhance performance of endurance athletes.
(5) Trans-epithelial transport of the betalain pigments indicaxanthin and betanin across Caco-2 cell monolayers and influence of food matrix.
(6) H+-coupled nutrient, micronutrient and drug transporters in the mammalian small intestine.
Thanks
Eric
eric@sur.co
Re: Evidence of Nitrates increasing nitric oxide production
We have no objection to findings reporting the beneficial effect of dietary nitrates on sport activities. The mechanism behind their potency has also been described and is rather specific for this class of compounds. Objectively, it needs to be also addressed that there are publications reporting that nitrates have limited or no effect on exercise (1-4). As described, nitrates were bioavailable but did not deliver efficacious effect. Addressing all the factors involved in these unexpected results may help understand reasons of limited efficacy of ingested nitrate products. We will be soon be releasing some further study results address some unexpected information and betalains vs. dietary nitrates.
Re: Plasma Bioavailabilty Study you referenced (https://www.ncbi.nlm.nih.gov/pubmed/26873098)
This manuscript refers to the Plasma bioavailability of nitrate from Beta vulgaris. Here the authors describe how beetroot juice provides NO in high concentration but betanin was barely detected in plasma regardless of its presence in supplemented material.
However, there are other studies showing that betalains are bioavailable after ingestion (for example from cactus pear or purified betalains as such). This suggests that bioavailability of betalains may depend on other factors, such as food matrix or on co-presence of other entities to some extent (for example sugars or even nitrates). Indeed, cactus pears contain relatively lower amount of sugars compared to beets. Also, cactus pears do not contain a significant amount of nitrates. Absence of nitrates and lower amount of glucose could be one of reasons why betalains from this material are bioavailable.
Furthermore, research on the mechanism of absorption of betalains has shown the involvement of membrane transporters and receptors such as MCT1, OATP2B1, MRP2 (5). Interestingly, various components including food elements may affect functioning of these receptors and carriers resulting in reduced or enhanced absorption of betalains (6).
Therefore, results reported in the publication cited by you do illustrate negative effect of red beet matrix on bioavailability of betalains present in that material. Your observations are valid and well-founded and we would like to mention that we are already addressing this issue in scientific detail. In order to understand how our AltRed works,, we are investigating the bioavailability of betalains from our extract (12.5mg of betalains per 50mg dose) comparing it to the equivalent amount of betalains in red beet juice, following a cross-over clinical study model that we will publish. Study subjects will be receiving either our extract or red beet juice after a washout period.
So far, results from clinical trials seem to indicate that betalains from our product are highly bioavailable and that our product significantly increased sport performance in supplemented subjects. We would like to mention that the mechanism of action that involves the bioavailability of the components of our product will be quite different from the mechanism pertaining nitrates or other supplements for sport performance. We are focusing on betalain-specific mechanisms improving sport performance activities completely independent of nitrates.
In the manuscript you mentioned, there are a couple of factors that were not taken into consideration. The first, the analysis was only performed in EDTA-plasma, under the assumption that betalains would be circulating in blood as free molecules. The second, when there is an excess of betalains, these tend to be eliminated through urine and there were no determinations of betalain content reported in this study. Additionally, only betanin was determined in plasma samples. It is well documented that betanin is one of the most abundant betalains in beetroot, however, bioavailability of other betalains present in beet was not measured.
It is mentioned here since rate of absorption of different betalains seems to be different. We would like to mention that we are studying the bioavailability of betalains from our extract and our preliminary results are similar to results previously reported by research group investigating bioavailability of betalains from cactus pear. Our preliminary results show that betalains from our product are highly bioavailable within 90 minutes after ingestion (manuscript in preparation). Our next step is to describe the kinetics and efficiency of betalain absorption and how it can be correlated with improvement of sport performance.
RE: The question I posed about whether it might be the betalains and not the nitrates that are producing these performance benefits
We have determined the amount of betalains available in our product. We also know that these betalains are bioavailable since we have previously seen results about bioavailability of betalains from different sources. Therefore, we focused on efficacy first. To this date, four studies have been completed by three different research groups (3 published, one in review) showing that there is a beneficial effect on exercise performance. In two separate studies, subjects were preloaded with our product with one last dose 1.5 hours before exercise. Results of these studies show statistically positive effect (power output, speed, distance). Furthermore, we also saw the increase in exercise performance in sedentary subjects after a single dose. All these studies were double blind, and placebo controlled.
As previously mentioned the mechanism of action of betalains on sport performance is quite different compared to other sport products including nitrates and requires more discovery clinical research. We are pursuing such research and results of this work that will be submitted for publication in 2018.
Our research is focused on betalain-specific effect on sport performance. Following this path, we assume that red beets contain two very different classes of chemical entities affecting sport performance; nitrates and betalains. According to our hypothesis, bioavailablity of betalains in presence of nitrates and/or sugars in high concentration is highly inhibited. Therefore bioavailability of betalains as well as stimulatory effect of betalains on sport performance needs to be investigated in absence of nitrates.
Re: Your study about the profile content of Betalains in Plasm (https://www.ncbi.nlm.nih.gov/pubmed/29638119)
This paper is indeed interesting. Results published are raising an interesting question – how much betalain in blood is needed to provide beneficial effect on exercise. Preliminary results show that nM range is sufficient but more research is needed to conclude and to publish. Another question could be whether study subjects involved in this study could have any positive effect on sport performance if asked to exercise. Based on our observations while performing clinical studies as published – they could. The effect of Betalain is showing to be exercise induced and we will continue to publish on this.
Furthermore, people who are reporting beeturia after eating red beets (or drinking beetroot juice) do not have beeturia after taking our product. Such an observation may lead to possibility that other components not present in beets are determining whether ingestion of betalains in large quantities may result in beeturia. Based on published results, metabolism of iron may play crucial role in developing symptoms of beeturia (2 references are attached)
Again, thanks for the discussion! Would love to discuss further over the phone or next time our team is in your area! Here's a list of the references used above
(1) No improvement in endurance performance after a single dose of beetroot juice.
(2) Influence of acute dietary nitrate supplementation on 50 mile time trial performance in well-trained cyclists.
(3) Dietary nitrate does not enhance running performance in elite cross-country skiers.
(4) Sodium nitrate supplementation does not enhance performance of endurance athletes.
(5) Trans-epithelial transport of the betalain pigments indicaxanthin and betanin across Caco-2 cell monolayers and influence of food matrix.
(6) H+-coupled nutrient, micronutrient and drug transporters in the mammalian small intestine.
Thanks
Eric
eric@sur.co