Orotic Acid a promoter of Liver Cancer?

[Pax]

Studies on liver tumor promotion in the rat by orotic acid: dose and minimum exposure time required for dietary orotic acid to promote hepatocarcinogenesis -- Laconi et al. 14 (9): 1771 -- Carcinogenesis

Inhibition of DNA synthesis in primary cultures of hepatocytes by orotic acid -- Laconi et al. 9 (4): 675 -- Carcinogenesis

Other studies have noted OA's effect on the liver of causing impaired fatty acid synthesis and increased cholesterol synthesis

Early effects of dietary orotic acid upon liver lipid synthesis and bile cholesterol secretion in rats -- Tokmakjian and Haines 26 (4): 478 -- Journal of Lipid Research

So is OA really a powerful carcinogen that is being marketed/sold to us as some type of great bodybuilding supplement?

[rippedforce63]

Hmm, I wonder if any reps from man visit this forum. I'm pretty sure they use orotic acid in a couple of their products and I've heard alot of positive feedback on it.

[Rostam]

Scary studies!

[RenegadeRows]

Interesting. I know alot of MAN's products do revolve around orotic acid

[joebo]

What is it used for?

[Rostam]

What is it used for?

Enter Orotic Acid!

Orotic Acid (OA) is a precursor of pyrimidine and nucleic acids which are vital for optimal cell functioning and energy metabolism. OA enhances and maintains ATP pools in three ways:

1. The production of ribose moieties (R-1-P and R-5-P) for the salvage or de novo synthesis of purine nucleotides by a process know as "ribose transfer". Many of you may remember ribose (a sugar component of ATP) supplementation being touted as an enhancer of high intensity repetitive exercise performance. For a quick recap on the energy producing pathways of ribose seen.

The way OA enhances the formation of ATP is by providing the direct precursor to phosphoribosylpyrophosphate (PRPP) a key energy-supplying compound in the de-novo synthesis of purine and pyrimidine nucleotides (I know that's a real mouthful). The reserve of PRPP is poor because of the low capacity of the pentose phosphate pathway. Therefore the generation of ribose-5-phosphate (R-5-P) the immediate precursor to PRPP ribose supply can be enhanced with OA and as a result greater ATP regeneration.

2. The second pathway is by increasing the pool of Uridine Monophosphate (UMP), which requires ATP to convert to further downstream pyrimidine nucleotides (UTP & CTP). By increasing the levels of these nucleotides the draw on ATP reserves to synthesize them is decreased thereby enhancing the availability of ATP for other metabolic process such as energy and contractile producing pathways.

3. The final pathway is by means of elevation of intracellular glycogen stores. These elevated glycogen stores generated from a greater uptake of glucose lead to an enhanced capacity for ATP resynthesis from anaerobic glycolysis.

What this means is more energy for hard working muscles. Evidence also suggests OA can be used to synthesize carnosine (the ultimate buffering nutrient) by elevating its natural precursor "beta-alanine". This is illustrated in the chart below:

More recent studies have shown OA supplementation enhances endurance performance and exercise capacity. OA also has been shown to augment muscle hypertrophy and to increase the contractile capacity of muscle.

This is from MAN orotine product page.

[Pax]

Granted... these are rat studies but who is going to run such a study on humans - to see if it promotes hepatocarcinogenesis.....

I guess this is what the supplement world has come to... lots of hype/marketing of products, and intentionally failing to fully disclose the harmful effects of said products. As I learn more and more... I being to realize that sometimes government control over the supplement industry, while it may be arcane, selective, and at times ridiculous, can sometimes work for the betterment of public health.

I find it wholly irresponsible on the part of those marketing these subtances, to intentionally and/or knowingly conceal from the public the fact that studies have shown their product to be a powerful promoter of liver cancer in several studies performed on rats.

Those manufacturing, distributing, and/or marketing this product should really consider utilizing a "good faith" practice in disclosing what studies have revealed to be harmful effects of their product, in addition to its "possible" health benefits. Some day, somebody will be seriously injured, if not killed, due to an irresponsible manufacturer, distributor and/or marketer of such products. And then the lawsuits will come. As an attorney.... heed my words and those marketing, distrubiting and/or marketing should take care to spare their own and their companies' financial ruin. It's very easy to "pierce the corporate veil" and go after a company owner's personal assets. So be smart!!!

[rippedforce63]

[CDB]

Wouldn't the dosing schemes in these studies require doses of OA around the 15-20 gram per day mark to start duplicating these effects? I don't think MAN products go that high in the standard dose. Not to mention they are rat studies. Chemicals can be harmful to rats and not to humans simply because there are differences in our system. One example that I seem to remember is some chemical reacting with another chemical in rat urine and causing cancer, yet this wasn't a problem for humans because our urine didn't contain the same chemical. Sorry to be vague, it's all I remember right now except that there was a major public scare involved. Stuff like that makes it hard to judge the relevance of studies like these, especially if they involve megadosing which I think these do.

[Rostam]

I do agree these studies are on rats and also do agree that they are probably using megadoses of the compound.
But come on! its cancer promoting effect showed up only after 10/20 weeks. People get scared and some health authorities concerned about artificial sweeteners cancer promoting effect although studies were not as clear as this one about their carcinogenic risk.

[TheUnlikelyToad]

Hmm, I wonder if any reps from man visit this forum.

Nope.

[CDB]

I do agree these studies are on rats and also do agree that they are probably using megadoses of the compound.
But come on! its cancer promoting effect showed up only after 10/20 weeks. People get scared and some health authorities concerned about artificial sweeteners cancer promoting effect although studies were not as clear as this one about their carcinogenic risk.

Never really looked at the sweetener studies as I don't really use them. But in the end there's really few chemicals which if taken in high enough doses and/or for a long enough time won't cause cancer in rats. A third of the rats are going to die of cancer anyway. Cause for concern? Well yeah, I wouldn't be sprinkling this stuff on my cereal in the morning. But I don't think MAN was out to kill people with their products, and I don't think they were actively hiding these studies from people.