Thank you for your feedback and concerns, we're always open to that! If I may, let me please share some insight into why we decided to acreoline in our product versus not, primarily I will go over the arguments against the negatives because the positives are the stimulant effects of energy, euphoria, and well-being, etc.
Let me first start off by saying that, there's no doubt that Betel Nut / Areca Nut is indeed a carcinogenic product. But what's important to note is that you can't backwards extrapolate i.e. saying that if Aceca Nut is carcinogenic and if acreoline is in aceca nut then it also must be carcinogenic. For this type of thing, you can forward extrapolate, for example saying nicotine is a carcinogen, nicotine is in cigarettes, therefore cigarettes are a carcinogen. But you cannot backwards extrapolate, using the cigarette example again, you can't say cigarettes are a carcinogen, cotton is in cigarettes (the filter part), therefore cotton is a carcinogen.
So essentially the first point I'm making is establishing that Betel Nut / Areca Nut is a carcinogen does not conclude that acreoline is a carcinogen. The 3rd link you provided
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4080659/, goes solely over the Betel Nut / Areca Nut and not acreoline. I agree that Betel Nut / Areca Nut is a carcinogen, but your concerns are not about Betel Nut / Areca Nut, it's about the acreoline in our product, so we cannot consider the 3rd linked article as evidence of acreoline being dangerous.
Next, let's address the 1st and 2nd article you linked. The 2nd article is mostly discussing the Betel Nut / Areca Nut and it's extract, again this is not our subject of conversation we need to focus on acreoline specifically. However, on page 105/240, it mentions the exact same study as the 1st article you linked. So for the 1st and 2nd link, it's mainly focusing on the first link study you posted titled "Arecoline tumorigenicity in Swiss strain mice on normal and vitamin B deficient diet.". This study is more valid to our current discussion because they used "arecoline hydrochloride" specifically, not a areca nut extract or parts of an areca nut but specifically arecoline, which is what we're interested in. Now below I have quoted the abstract and bolded the important parts:
"Arecoline, a major alkaloid present in betel nut, was administered daily by gavage feeding to Swiss male and female mice at a dose of
1 mg/day/mouse five times a week, either alone or in combination with KNO3 or KNO3 + lime. Swiss mice of both sexes kept on a vitamin B complex-deficient diet were tested in a similar manner and compared with those receiving a normal diet.
In the mice receiving a normal diet it was observed that arecoline induced tumors in 40% of males but failed to produce tumors in any of the females. Arecoline tumorigenicity in females was evident only when they received a vitamin B-deficient diet. Arecoline tumorigenicity was not evident in males when they were treated simultaneously with KNO3 + lime and kept on a normal diet. However, the same treatment administered to male mice kept on a vitamin B complex-deficient diet induced tumors in 39%."
Ok now let's break this down into the pieces that are relevant.
1. 1mg/day for 5 days. The average weight of a 6 week Swiss mouse (what was used in the study) is about 25 grams according to this:
http://www.criver.com/files/pdfs/rms/us-model-pricing/rm_rm_c_cfw_swiss_webster.aspx , just look at the graph on the left hand side, look at 6 weeks of age and the average is about 25 grams for a male swiss mouse. At 1mg/day for a 25 gram mouse, the equivalent dose for an average 90kg male (198 lbs) is 291mg based on human equivalent dosing, which is 58x the dosage of one serving of our product. This touches on your second quote talking about dosing, 58x is way more than 10x. I'd imagine taking 58x the dosage of our any of our DMAA products would be fatal. So my first counter-argument is that the study is looking at a dosage that is 58x the dosage of our product.
2. In the mice receiving a normal diet it was observed that arecoline induced tumors in 40% of males but
failed to produce tumors in any of the females. Why is that? Why was there 40% tumors in males but none in the females? Then continue reading the abstract and you'll see tumors in females when they had a vitamin B-deficient diet. Arecoline tumorigenicity seen in males when they were" treated simultaneously with KNO3 + lime and kept on a normal diet. However, the same treatment administered to male mice kept on a vitamin B complex-deficient diet induced tumors in 39%." This indicates there must be another factory at play. It's not just the arecoline because you range from 0-40% just based on their diet changing while still taking the acrecoline. You should especially be worried about why there was such a discrepancy? Why did were tumors not induced in females at all? This takes us to point 3:
3. The full article of the 1st link you posted is under a paywall, so the majority of this community doesn't have access to (not because they can't but because they don't want to pay the subscription fee haha). But the second link you gave that talked about that same study has this very important note: "
The Working Group noted the lack of information on the time of appearance of specific neoplasms and the inadequate reporting of the pathological findings. The lack of tumours in females was not explained." Now they don't specific who exactly the working group is (whether it's the researchers themselves or a 3rd party), but the in the scientific community generally a Working Group is "a scientific subject-matter experts who collaborate to determine best practices and to develop consensus standards" (
https://www.nist.gov/oles/scientific-working-groups). Going on that, this shows that there were some fundamental issues with reporting and data collection of the first study you linked. The Working Group also acknowledges the lack of explanation for lack of tumors in females, which is what is the first thing I noticed in that study. This commentary you won't find on the abstract, it's actually on the bottom of page 105 + to of page 106 of your second link. The inconsistencies of the study and inadequate data monitoring and collecting really puts the whole study in question.
Now, I've tried my best to elaborate and counter the arguments you have made, now it's my turn to show my evidence for my side.
1. Study A: "Evaluation of Arecoline Hydrobromide Toxicity after a 14-Day Repeated Oral Administration in Wistar Rats"
Full Study available here:
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0120165
Quick Background: 14 day study, 80 rats divided into four groups: a high-dose group (1000 mg/kg), medium-dose group (200 mg/kg), low-dose group (100mg/kg) and blank control group. Conclusion: "
The level of Ah (Arecoline Hydrobromide ) at which no adverse effects were observed was 100 mg/kg/day under the present study conditions.
Now what's really interesting here is that at 100mg/kg translates to 1460mg for a 90kg average male. But the article 1 you linked said that 1g/25g mice = 291mg/90kg humans caused tumors. But here we see a more recent study (April 2015) that has almost 5x the dosage is reported no adverse affects. This along with the Working Group note, really makes you question the results and data obtained from that first 1984 study.
Another interesting note, this 2015 study says in the conclusions: "Decreased body weight and food consumption were identified in all treated rats after 14 days of Ah administration. " This supports our inclusion in our fat burner.
This study is significant to our case because it is a shorter study, our Controlled Burn specifically says on the label to take the product on 2 week cycles. This corresponds exactly with the 14 day length of this 2015 study. The study does note "Based on the results of our analysis and the earlier acute toxicity test, long-term administration of high doses of Ah is likely to be toxic." But what's important to note is that our Controlled Burn product isn't intended to be used long term at high doses. You're not suppose to be taking this everyday, year round, taking 6-8+ capsules at a time. Even then, our product is dosed even a fraction of what these studies are doing. So we've build everything in that reflects the safety shown in this study.
2. Here's a really interesting study, just came out 4 months ago in Nov 2016:
https://www.ncbi.nlm.nih.gov/pubmed/27867011
It's kind of a hard read, but this Sci News article actually helps break it down a bit:
http://www.sci-news.com/medicine/arecoline-areca-nuts-anti-cancer-potential-04406.html
This totally flips things upside down, because now we have a very recent study showing that acreoline may actually have anti-cancer properties! But I think the statement at the end really sums up the acreoline debate:
“While we did not see obvious toxicity when treating mice with arecoline, more extensive pharmacokinetic and toxicology studies with arecoline and similar compounds are needed.”
In my personal opinion, and I share this with all my reps and athletes so they know, is that most of the ingredients in the supplement industry are grossly understudied. There's just not enough funding, money and motivation to do these extensive studies on thousands and thousands of dietary supplements. And even when done, usually it's for medicinal purposes and not workout/fitness purposes. We can try to extrapolate where we can, but we have to be careful about the claims we're making and the conclusions we're extrapolating. I could go on about how we approach choosing what ingredients to use, but I go into detail about this in our upcoming SuppTalk podcast to be released this Friday 17th (
http://www.podcastgarden.com/podcast/supptalk)
double s
But end of the day, we are a customer sanctification and customer demand driven company. If the majority of people interested in our product are against acrecoline, we'll take it out of the next production run, no problem. However, I've given my personal counter-points as well as supporting points as to why we have it in there now. I'm very open to feedback and maybe I missed something! I'm a supporter of our products, and I wouldn't push anything I don't believe in (this is why we do not and will not carry pro-hormones). I acknowledge there's lots of studies out there for the Areca nut as well as acreoline, but at this point in time I have not seen the conclusive evidence to show that our dosing amount and regiment will cause any long term negative affects.
Thank you to everyone who has read this entire post. I'm passionate about our brand and will do everything thoroughly to show you why I think we products with great features and benefits.
