Talk:Protandim/Archives/2009/August

Reference to 2008 review published in the British journal of nutrition

I assume Tim Vickers added this reference. Thank you. It is an appropriate addition to the article. A pdf is available on-line which I added to the reference. However, one comment in the Wikipedia article is as follows: the review "...commented that changes in TBARS levels and increases in the levels of antioxidant enzymes in response to a treatment does not indicate that the treatment has an antioxidant effect, since the same responses are produced by pro-oxidant compounds that induce oxidative stress". I cannot find anything in the review consistent with this comment. The abstract does say: "A number of currently used biochemical measurements aimed [at] determining the total antioxidant capacity and oxidised lipids and proteins are carried out under unphysiologcial conditions and are prone to artefact formation. Probably the most reliable approaches are measurements of isoprostanes as a parameter of lipid peroxidation and determination of oxidative DNA damage." This comment is relevant to the Protandim study. However, the abstract also says: "This approach is based on the assumption that protection towards ROS is due to scavenging, but recent findings indicate that activation of transcription factors which regulate genes involved in antioxidant defence plays a key role in the mode of action of AO." This comment seems to be supportive of the conceptual basis of Protandim.(Entropy7 (talk) 15:33, 11 August 2009 (UTC))

See page 33 of that paper. Tim Vickers (talk) 17:08, 10 August 2009 (UTC)

As mentioned above, measurements of the induction of antioxidant enzymes do not provide reliable information for protective effects as they can also be induced by ROS themselves and their up regulation may reflect prooxidant effects.

Added "not a reliable indication". I think the statement of the authors of this paper was a little more tentative in its wording. (Entropy7 (talk) 14:47, 11 August 2009 (UTC))

That's fine. Tim Vickers (talk) 19:17, 10 August 2009 (UTC)

Sorry, didn't scan the paper well enough before commenting on it. It is 44 pages. Does this have a great impact on the credibility of study? Off hand, I would say, it is unlikely that 29(33) people happen to be accidentally exposed to significant levels of pro-oxidant during the evaluation period. At the end of the day, all that can be said is something like, "such-and-such study suggests that something-something may be true, but more evaluation is needed".(Entropy7 (talk) 15:33, 11 August 2009 (UTC))

The point is that the compounds in protandim may have pro-oxidant effects. The available data do not exclude that possibility. Tim Vickers (talk) 15:57, 11 August 2009 (UTC)

It does not seem like any of the ingredients are noted for being prooxidants when acting separately. Taken together, I suppose they might be exerting an effect that is actually prooxidant. I wonder, also, if the over expression is not significant if it does not occur at the mitochondrial level. (Entropy7 (talk) 20:11, 11 August 2009 (UTC))

See PMID 15465643 and PMID 17640567 for discussion of curcumin's pro-oxidant activity. It is also an inhibitor of thioredoxin reductase, an antioxidant enzyme (PMID 15879598). In general, I'd say it was still unclear if flavonoids have an overall anti- or pro-oxidant effect in vivo (see PMID 12126798 and PMID 18284912). Tim Vickers (talk) 20:20, 11 August 2009 (UTC)

Deleted Comment

At one point, I added a comment stating that overexpression of catalase and SOD genes has been shown to increase lifespan of various species and included various references in support. This comment has since been deleted. However, it shows that the basic concept of Protandim has significant precedence in the literature. It is appropriate to the topic and should be restored, though the "clinical study" section may not be the best place for it.(Entropy7 (talk) 19:15, 29 July 2009 (UTC))

This was a bit misleading. The results are mixed, with results in flies and mice suggesting one thing and results in worms suggesting another. The fly data has also been recently questioned (PMID 12743125). It is a bad idea (as the authors of the protandim paper did) to cite part of the literature to give a misleading picture of the whole field. This 2009 review PMID 19411855 could be good to cite, as it gives an up-to-date picture of the current state of the oxidative aging hypothesis. Another more positive review is PMID 16677102, although this does still note that antioxidants have no effect on lifespan. Tim Vickers (talk) 17:02, 10 August 2009 (UTC)

Stoichiometric vs. Scavenging

Recently, Tim Vickers deleted the word "stoichiometric" from the description of more conventional compounds considered to be antioxidants. Perhaps "scavenging" is a better term. This term was used in the reference that Tim submitted. I think it is still a meaningful concept. I think it is a significant aspect of the rationale behind a part of anti-oxidant therapy that has been largely discredited. (67.176.199.104 (Entropy7 (talk) 21:21, 29 July 2009 (UTC))

This isn't a meaningful way of classifying antioxidants. For example, take glutathione. This compound can react directly with reactive oxygen species, or supply electrons to glutathione peroxidase. You can't class this compound as just a "scavenger" as it is also part of an enzymatic system. The best way of looking at antioxidants is as an interacting network, with each component contributing to the activity of the system. Tim Vickers (talk) 16:58, 10 August 2009 (UTC)

Article Intro

In the introduction, there is a sentence that reads, "There is no acceptable evidence that it improves health." Perhaps it should read, "There is no conclusive evidence that it improves health." which better reflects a degree of uncertainty regarding determinations that can be made about this product. (Entropy7 (talk) 14:08, 24 August 2009 (UTC))

There is no conclusive evidence that it is harmful to health either. There is no conclusive evidence either way. This sentence would be better as focusing on the lack of convincing evidence on both positive or negative effects. Tim Vickers (talk) 17:00, 24 August 2009 (UTC)

So it might read, "There is no conclusive evidence that it affects human health." The animal study showed that it reduces effects of a carcinogen on mice. I wonder why they haven't done a lifespan study on mice They've raised millions in venture capital funding. (Entropy7 (talk) 19:01, 24 August 2009 (UTC))

Probably because most of the people in the company have backgrounds in pyramid marketing. If they're making money with their current product and marketing scheme, why risk doing studies that might demonstrate that this nostrum is useless? Tim Vickers (talk) 19:20, 24 August 2009 (UTC)

I imagine that scenario is possible. This Wikipedia article comes up at the top of the list of a Google search for "Protandim" now (although that will vary from day to day). Perhaps that will put some pressure on them to continue to work to validate their product. (67.176.199.104 (talk) 23:46, 24 August 2009 (UTC))

Here is one issue we already went over once before. "Protandim is a patented[1] dietary supplement that allegedly increases the body’s antioxidant defenses. It is not approved by the US Food and Drug Administration to diagnose, treat, cure or prevent any disease.[2] There is therefore no convincing evidence that it has either positive or negative effects on the health of those who take it." It is a GRAS product and carries the obligatory legal disclaimer. But that fact in and of itself does not necessarily lead to the conclusion that "it has either positive or negative effects on the health of those who take it." Many GRAS products are questionable. I suppose that this is one of them. However, it is specious to make determinations about a product based on a regularory classification. So I will take out the word, "therefore". (Entropy7 (talk) 19:12, 24 August 2009 (UTC))

That's fine. Tim Vickers (talk) 19:20, 24 August 2009 (UTC)

I noticed when I Google "protandim" on Internet Explorer the Wikipedia article comes up at position number 4 but when I Google it on Firefox, it comes up in the number 1 position. Up to this point, I wasn't aware that the browser made a difference. Also, a note on Dr. Harriet Hall, here is a very recent article she wrote on Protandim, where she is stating a very different viewpoint from the item she wrote 4 years ago. I have seen items stating that there is a very strong synergy between the ingredients by orders of magnitude but nothing that could be considered proper documentation for a Wikipedia article. I get the impression that there is unpublished research data. Personally, I hope it good rather than bad. Perhaps the Wikipedia article will encourage them to expedite publication. It seems like the inventor of Protandim is Paul Myhill. He gives an account of the development here and comments that all of his earnings go to charity. (Entropy7 (talk) 20:21, 25 August 2009 (UTC))

Seems like that first blogger concurs with the general view of this article, good to see our work being reviewed approvingly. As to that second interview, his claim that "Big Pharma (through its proxy, the FDA) doesn’t allow supplements to make any disease claims.." is absolutely false. If you have the data, you can make the claim. However, if you have no data, you can still market your product as a "supplement". I'm not at all impressed by his attempt to dance around the facts there. Tim Vickers (talk) 20:31, 25 August 2009 (UTC)