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Supplement combination, good or harmfull?


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#1 medievil

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Posted 17 August 2010 - 12:11 AM


I beleive a few months ago a video appeared of a guy presenting he's latest life extension experiment with several substances including methylene blue, SAMe en other stuff.

He also mentioned that small experiments showed that when combining supplements the results werent any better, quite the opposite and most benefits were blunted, i dont remember any details (maybe someone can help).

Also i remember someone mentioning that LEF was doing experiments on mice with a ton of supplements togheter and that they ended up giving up because heroic combo's barely showed any positive effect (i havent seen any source for this statement so i would disregard this as truth unless someone can show a link for this claim, my first example did come from a credible source).

The professor in the first thread mentioned he tougth it was because when combining supplements the doses need to be lowered.

Point of my thread is to discuss the evidence behind or against combination of supplements and to conclude wheter its best to stick with one supplement or build up a stack.

As many ppl here build stacks (wich can be pretty heroic imo) i tought it was important to discuss this, as seen with my latest posts in deprenyl i feel that we need to discuss potential harmfull effects in detail to make sure we can get positives.

#2 niner

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Posted 17 August 2010 - 12:26 AM

I beleive a few months ago a video appeared of a guy presenting he's latest life extension experiment with several substances including methylene blue, SAMe en other stuff.

He also mentioned that small experiments showed that when combining supplements the results werent any better, quite the opposite and most benefits were blunted, i dont remember any details (maybe someone can help).

What kind of supplements are we talking about here? Vitamins and minerals? Nootropics? Others? It is really going to depend on the exact combinations. One stack with a hundred compounds might be fine, while another one with only two or three might be dangerous.

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#3 medievil

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Posted 17 August 2010 - 12:35 AM

I'm afraid i dont remember, he was talking about life extension combinations and also about a combo for cancer that showed little results compared to the substances on their own.

I will have to find that video again (anyone has a link?) to get more info, (also a reason why i made this thread, to discuss what combo's are great and wich one's will suck.

One stack with a hundred compounds might be fine

Its about stacks that are technically fine, but produce little results in comparsion to one of the included supplements on its own (eg we would be taking a ton of sups for nothing).

But i will need to find that video to go further into detail, i know SAMe, methylene blue, metforin and a ton of other stuff was being tested, it was one of the biggest study's coming up.

#4 capsun

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Posted 17 August 2010 - 01:28 AM



5:20-8:00
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#5 medievil

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Posted 17 August 2010 - 01:35 AM

@capsun, excellent that was what i was looking for :).

#6 niner

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Posted 17 August 2010 - 02:55 AM

Spindler talked about Wang's results with tumor drugs, where the optimum concentration of compounds in combinations was lower than with the individual compound. That makes sense because you are typically stressing the healthy cells to the limit with any one of the compounds. It makes sense that you would need to reduce concentrations there. I would argue that this situation is very different from normal dosing of supplements. Spindler wasn't very impressed with the results they had seen with their combinations of life extending drugs. A lot of those compounds were synthetic pharmaceuticals. They might have been seeing additive toxicities; hard to say. If all of them are curve squaring, the curve can only get so square. But these sorts of compounds are pretty different from the vitamins, minerals, food extracts and other micronutrients that people are commonly stacking. There are undoubtedly some problems with combinations of compounds. Some that we know about are inhibitors of metabolic enzymes that alter the concentration of other compounds that are metabolized by those enzymes. (Sometimes this is a good thing.) Too many compounds with the same mechanism of action might overload a system or pathway; too many antioxidants, for example. Recently there was a report that GTE interfered with the action of pomegranate extract in some in vitro assay. May or may not be significant, but it's an example. No doubt others will turn up. I suppose it's a reasonable principle to consider that each compound you add to your stack geometrically increases the number of combinations to consider.

#7 medievil

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Posted 17 August 2010 - 03:36 PM

Excellent reply niner, that answers a few questions.

Are you away of any other studies that studied combinations of compounds for eventual synergetic effects?

#8 aLurker

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Posted 17 August 2010 - 04:30 PM

Very interesting thread.

What kind of stacks would have synergy? Specific examples are welcome.

Just to discuss this more generally:
Are we looking for supplements with mechanisms which are;
1) related and might aid each other (synergy like Piracetam and choline might have),
2) which are similar to potentate the effects
3) entirely different to avoid interactions?

Regarding synergy from related mechanism: it seems very hard to predict which supplements would have this in theory and practise. I would really appreciate if anyone could oblige medievil's request for studies regarding this. Very few combinations seem to have an equivocal synergy supported by science.

Personally I tend to avoid supplements with similar mechanisms since their effects together often seem to fall in between diminishing returns and directly harmful. Niner mentioned green tea extract and pomegranate as an example where there is interference. A more serious example would be combining different MAOIs. There is a thing such as too much of the good stuff and where that lines goes is hard to tell when you can't predict the accumulative effect. Stacking racetams seems quite common here despite a certain overlap in mechanisms and I'd very much like hear the rationale behind this no matter if it's technical or anecdotal. Many seem to go with how different combinations make them feel although this isn't a clear indicator of long-term healthiness.

Right now I'm personally leaning towards supplements with as distinctly different mechanisms as possible to avoid interactions and to hopefully maximize the effects of each individual supplement as they hopefully don't interfere with each others effects.

What are your thoughts or motivations for your own supplemental strategies?
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#9 medievil

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Posted 18 August 2010 - 06:25 PM

Study in favor of supplement combinations:
http://inhumanexperi...s-lifespan.html

Ingredient Mg
Bioflavonoids 7.93
Vitamin A (beta-carotene) 0.22
Vitamin B1 0.31
Vitamin B3 0.31
Vitamin B6 0.61
Vitamin B9 0.006
Vitamin B12 0.02
Vitamin C 3.51
Vitamin D .0002
Vitamin E 3.27
Rutin 3.05
Chromium picolinate 0.003
Magnesium 0.46
Manganese 0.19
Potassium 0.18
Selenium 0.0005
Acetyl L-carnitine 1.47
Alpha-lipoic acid 1.83
Aspirin 1.32
Coenzyme Q10 0.61
Cod liver oil 12.20
Flax seed oil 12.20
Garlic 0.04
Ginger root extract 6.00
Ginkgo biloba 0.18
Ginseng 6.31
Green tea extract 4.88
L-Glutathione 0.31
Melatonin 0.007
N-acetyl cysteine 3.05

Which are pretty common supplements and appear to be harmless and synergetic when combined.

Edited by medievil, 18 August 2010 - 06:25 PM.


#10 medievil

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Posted 18 August 2010 - 11:35 PM

Evidence showing synergy between curcumin and resveratrol:

Curcumin synergizes with resveratrol to inhibit colon cancer.
Majumdar AP, Banerjee S, Nautiyal J, Patel BB, Patel V, Du J, Yu Y, Elliott AA, Levi E, Sarkar FH.

John D. Dingell VA Medical Center, 4646 John R, Room B-4238, Detroit, MI 48201, USA. a.majumdar@wayne.edu
Abstract
Development and progression of many malignancies, including colorectal cancer, are associated with activation of multiple signaling pathways. Therefore, inhibition of these signaling pathways with noncytotoxic natural products represents a logical preventive and/or therapeutic approach for colon cancer. Curcumin and resveratrol, both of which inhibit the growth of transformed cells and colon carcinogenesis, were selected to examine whether combining them would be an effective preventive and/or therapeutic strategy for colon cancer. Indeed, the combination of curcumin and resveratrol was found to be more effective in inhibiting growth of p53-positive (wt) and p53-negative colon cancer HCT-116 cells in vitro and in vivo in SCID xenografts of colon cancer HCT-116 (wt) cells than either agent alone. Analysis by Calcusyn software showed synergism between curcumin and resveratrol. The inhibition of tumors in response to curcumin and/or resveratrol was associated with the reduction in proliferation and stimulation of apoptosis accompanied by attenuation of NF-kappaB activity. In vitro studies have further demonstrated that the combinatorial treatment caused a greater inhibition of constitutive activation of EGFR and its family members as well as IGF-1R. Our current data suggest that the combination of curcumin and resveratrol could be an effective preventive/therapeutic strategy for colon cancer.



#11 aLurker

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Posted 19 August 2010 - 01:10 AM

Thank you for that interesting study.
I feel it is important to note that there are a lot of possible permutations with a laundry list of supplements such as that one. We can't be sure which supplements were responsible for that 11% of extra life, some might have been harmful while others might have exceeded 11% on their own. If they tested other combinations with exactly the same methodology we would have much more to work with. However it does show that combinations of supplements might give a net benefit but it doesn't really tell us much about how we should compose our stacks.

Much of the supplements listed have different mechanisms and there doesn't seem to be any obvious interactions which I can see although I must profess that I'm quite ignorant about a couple of supplements there. You might call the supplements "synergetic" but as I hypothesised earlier perhaps the reason they work well together is because they don't mess that much with each other. Admittedly that could be viewed as a kind of synergy though since it might increase the chance of the benefits being somewhat additive. I could be mistaken though and anything which might steer us in the right direction here would be much welcome.

#12 niner

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Posted 19 August 2010 - 03:43 AM

Study in favor of supplement combinations:
http://inhumanexperi...s-lifespan.html

[30 common supplements]

Which are pretty common supplements and appear to be harmless and synergetic when combined.

We can't really tell from the data whether or not there is any synergy, that is, any two of these are greater than the sum of their individual effects. We also can't tell if any of these are harmful. For all we know, If several of these substances were removed, the animals might have lived even longer. What we know is that for a set of healthy (meaning non-transgenic; we know nothing about their actual state of health) mice, this protocol resulted in an 11% lifespan increase compared to the unsupplemented mice.

The combination of 30 substances was a net win; if there were any interferences between compounds, they weren't bad enough to abolish all benefit. That's good, but it's not quite the same as proving there are no interferences.

There are ways to create apparent synergies that might not be meaningful. Imagine a population that is deficient in two different micronutrients. If you supplement either one of them, but not both, you will still have a deficiency. When you supplement both, health and lifespan may improve substantially. I don't think that represents a synergy, it just means you finally achieved good nutrition.

#13 medievil

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Posted 29 August 2010 - 11:27 PM

Bump,

I'm probably going for the combo of curcumin and resveratrol, wich work synergetically against cancer in the study posted above, altough that doesnt mean they will synergetically work against aging i feel comfortable about this combo. If they act as antioxidants i will probably cycle on and off to prevent that their antioxidant effects counteract the health benefits induced by excercise.

For all we know, If several of these substances were removed, the animals might have lived even longer.

Yes, thats a good point niner. Combining supplements is a bit tricky, i'm gonna keep it minimal.

Edited by medievil, 29 August 2010 - 11:31 PM.


#14 kismet

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Posted 30 August 2010 - 12:24 PM

The mice were not healthy per definitionem. Health is gauged from max. and avg. life span (and pathology if the rodents actually reach those life spans or thereabouts). In this study the max. life span of any group was lower than the avg. life span of a healthy, well-husbanded strain. Irrelevant for healthy aging, the study can only indicate that the employed cocktail is not outright toxic.
(although, some of the functional endpoints may be of some limited interest to us)

The resveratrol/curcumin study is even worse. I shudder at the thought of using in vitro or xenograft evidence. Animal models in oncology are hell. No guarantee that they translate to humans and when they do they apply to cancer patients: do you have colon cancer?

We must look at human evidence or *good* animal models.

Edited by kismet, 30 August 2010 - 12:26 PM.

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#15 medievil

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Posted 30 August 2010 - 01:19 PM

The mice were not healthy per definitionem. Health is gauged from max. and avg. life span (and pathology if the rodents actually reach those life spans or thereabouts). In this study the max. life span of any group was lower than the avg. life span of a healthy, well-husbanded strain. Irrelevant for healthy aging, the study can only indicate that the employed cocktail is not outright toxic.
(although, some of the functional endpoints may be of some limited interest to us)

The resveratrol/curcumin study is even worse. I shudder at the thought of using in vitro or xenograft evidence. Animal models in oncology are hell. No guarantee that they translate to humans and when they do they apply to cancer patients: do you have colon cancer?

We must look at human evidence or *good* animal models.


What your saying is pretty much the reason i made this thread, there barely is any data on supplement combinations and i wont be suprised that combinations turn out to be harmfull.

Human data is best, but what do we have on human data? We know that antioxidants inhibit the health benefits of excercise in humans, and most supplements people here take supplements that are antioxidants, another thing to think about. (i also made a thread on that subject).

Edited by medievil, 30 August 2010 - 01:40 PM.


#16 medievil

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Posted 28 October 2010 - 02:40 AM

Right now the only things i'm taking that have several neuroprotective and health promoting effects are candersartan and NAC, now i just ran across this study:

Antioxid Redox Signal. 2008 Dec;10(12):1999-2008.
N-acetylcysteine abolishes the protective effect of losartan against left ventricular remodeling in cardiomyopathy hamster.
Matsuhisa S, Otani H, Okazaki T, Yamashita K, Akita Y, Sato D, Moriguchi A, Iwasaka T.
The Second Department of Internal Medicine, Division of Cardiology, Kansai Medical University, Moriguchi City, Japan.

Oxidative stress mediated by activation of angiotensin II type-1 receptor (AT(1)R) plays a crucial role in the progression of heart failure. We investigated the effect of N-acetylcysteine (NAC) and an AT(1)R blocker on oxidative stress and left ventricular (LV) remodeling in BIO14.6 cardiomyopathy hamsters. The cardiomyopathy hamsters were treated with NAC or the AT(1)R blocker losartan for 20 weeks. Although NAC and losartan inhibited oxidative stress and upregulation of iNOS in the cardiomyopathy hamster heart, only losartan inhibited LV chamber dilation, myocardial fibrosis, and LV dysfunction in the cardiomyopathy hamster. Co-treatment with NAC abolished the protective effect of losartan against LV remodeling associated with inhibition of phosphatidylinositol 3-kinase (PI3K)/Akt and eNOS activation. An iNOS inhibitor 1400W or a nonselective NOS inhibitor Nomega-nitro-L-arginine methyl ester (L-NAME) exacerbated LV remodeling in the cardiomyopathy hamster. However, L-NAME but not 1400W abrogated losartan-mediated inhibition of LV remodeling. These results suggest that redox-sensitive upregulation of iNOS plays a crucial role in preventing LV remodeling in the BIO14.6 cardiomyopathy hamster. Losartan inhibits LV remodeling by switching the cardioprotective mechanism from iNOS- to eNOS-dependence, but NAC abolishes the protective effect of losartan by inhibiting redox-sensitive activation of PI3K/Akt and eNOS in the cardiomyopathy hamster.

PMID: 18665799

I'm only taking 2 things and there's allready one abolishing some protective effects of another one, this study confirms that my worries about supplement combinations are warranted and that one or several easily abolish the benefits of a bunch other ones, making excess combination really questionable.

#17 niner

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Posted 28 October 2010 - 02:59 AM

Well, yeah, but it's in the "cardiomyopathy hamster". This model is pretty far from a reasonably healthy human. If you look around the forums, you can probably find some better reasons not to take NAC, though.

#18 medievil

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Posted 28 October 2010 - 03:03 AM

Well, yeah, but it's in the "cardiomyopathy hamster". This model is pretty far from a reasonably healthy human. If you look around the forums, you can probably find some better reasons not to take NAC, though.

That model is far from a reasonable healthy human but serves as an excellent example how supplement combination can easily by inferior to taking only one supplement at a time.

I wont keep on taking NAC, i just started it after reading some positive anecdotals on it improving visceral fat loss (and a positive rodentstudy) i'm weight lifting 4 times a week, just wonna see what it will do

Edited by medievil, 28 October 2010 - 03:07 AM.


#19 chrono

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Posted 28 October 2010 - 10:44 AM

Yeah, read some of krillin's posts in NAC poll part 2. I save it for when I'm taking a bunch of dopamine precursors/releasers, drinking, etc.

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#20 medievil

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Posted 28 October 2010 - 02:27 PM

Yeah, read some of krillin's posts in NAC poll part 2. I save it for when I'm taking a bunch of dopamine precursors/releasers, drinking, etc.

The extensive history of human use of NAC and the lack of even a single case report makes me doubt that NAC is able to cause PAH in humans at reasonable doses. Still i'm not convinced of nac as a supplement that i should add to my regime, i'm just trying it out to see wheter it can help reduce some visceral fat :cool: .

Once i get resveratrol and curcumin back its back out, i'm too concerned of it abolishing the benefits of my other supplements (or any other supplement for that matter wich is why i stay with curcumin and resveratrol only, the less supplement the less likely i'm gonna get interactions).

Edited by medievil, 28 October 2010 - 02:28 PM.





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