121 replies to this topic

[timar]

Regarding krillin's regime:

 

The mechanism by which PEG protects against colon carcinogenesis is most probably a purely physical one, due to its action as an osmotic laxative*. You can very likely get an even better protective effect from inulin or lactulose, which have a laxative effect comparable to PEG but are also partially fermented by lactobacilli and bifidobacteria and hence provide all the additional benefits of a potent prebiotic.

 

I get 5 g of both inulin and lactulose a day from one cup of my homemade synbiotic yogurt. It has a really nice effect on my poop

 

I wouldn't take that much vitamin E/tocols. It may interfere with hormesis (irrespective of the form).

 

It seems like bit of an irony to me to ridicule a dose of 400 mg of turmeric as homeopathic while taking 1 g of flax seed oil

 

*although the RR from the study your cite seems remarkable, don't forget that has been observed in chronically constipated patients. The most frequent cause of chronic constipation is a crappy diet. I think it is unlikely that a laxative will provide any additional RR for someone eating a largely plant based, fiber-rich whole-food diet producing at least one bowel movement a day.

Edited by timar, 11 October 2014 - 04:54 PM.

[krillin]

Is that elemental 5mg Li?
No magnesium, carnitine or RNA?
I think resveratrol is way over hyped (like vitamin E, which I only take because it is in the LEF mix). Very unlikely that resveratrol can substitute for lipoic acid, since the later sources a coenzyme.

 

Yes, 5 mg of elemental lithium. I used to try to quarter the pills to get 1.25 mg/day but they shatter too easily. Lithium's half-life is short (1-3 days) so I don't think it could be an intermittent supplement.

 

I get more than enough magnesium from diet and the butyrate supplement. Is there any evidence to support exceeding 500 mg/day? (I'm actually getting more than 500. I discounted the nut and oat magnesium some to account for the phytate inhibition of absorption.)

 

Carnitine supplements are poorly absorbed (ALCAR is even worse) so you get the TMAO risk. I'll settle for what I get from meat and endogenous synthesis until we have more information.

 

RNA would provide nucleic acids and ribose to fuel cancer proliferation.

 

Supplemental lipoic acid is for Nrf2, PGC-1alpha, AMPK, etc. which resveratrol also does. Lipoic acid does not seem to stick around in the body to make a coenzyme. Giving 1 mg to humans resulted in 91-99% urinated out within 24 hours. Furthermore, supplemental lipoic acid could not substitute for knocked-out endogeneous synthesis in mouse embryonic development. "The early embryonic death of Lias^−/− mice that we observe suggests that free LA cannot be used to form the lipoic acid moiety of E2-containing enzyme complexes or that LA cannot be transported into mitochondria in mice even though it can probably pass through the placenta."

 

In ATBC, prostate cancer risk was lowest for those who got the low-dose vitamin E (50 mg) and had the highest baseline vitamin E and gamma E intake. 100 microM of vitamins C or E don't interfere with Nrf2 the way NAC and GSH do, and I'm taking less than the amount required to get to 100 microM of either, so I don't think I'm taking much of a hit to hormesis.

Edited by krillin, 11 October 2014 - 10:46 PM.

[krillin]

Regarding krillin's regime:

 

The mechanism by which PEG protects against colon carcinogenesis is most probably a purely physical one, due to its action as an osmotic laxative*. You can very likely get an even better protective effect from inulin or lactulose, which have a laxative effect comparable to PEG but are also partially fermented by lactobacilli and bifidobacteria and hence provide all the additional benefits of a potent prebiotic.

 

I get 5 g of both inulin and lactulose a day from one cup of my homemade synbiotic yogurt. It has a really nice effect on my poop

 

I wouldn't take that much vitamin E/tocols. It may interfere with hormesis (irrespective of the form).

 

It seems like bit of an irony to me to ridicule a dose of 400 mg of turmeric as homeopathic while taking 1 g of flax seed oil

 

*although the RR from the study your cite seems remarkable, don't forget that has been observed in chronically constipated patients. The most frequent cause of chronic constipation is a crappy diet. I think it is unlikely that a laxative will provide any additional RR for someone eating a largely plant based, fiber-rich whole-food diet producing at least one bowel movement a day.

 

Who negged Timar for this? I had to bring it back to zero.

 

PEG has an effect on p21 that reduced proliferation and the authors called it chemopreventive.

 

1 g of flaxseed oil was all that was required to reach my goal for calculated LCPUFA membrane composition. In the calculaton of membrane LCPUFA, it lowered n-6 from 61 to 60, lowered DHA from 27 to 25, and increased EPA+DPA from 12 to 15 compared to taking the EPA/DHA supplement alone. Adding more flaxseed oil would lower DHA more than I would like.
 

[blood]

Hi Krillin,

What are your thoughts, in a nutshell, on

- melatonin

- aspirin

- so-called bioactive forms of folate

(some things you don't take)

 

 

[Michael Price]

Is that elemental 5mg Li?
No magnesium, carnitine or RNA?
I think resveratrol is way over hyped (like vitamin E, which I only take because it is in the LEF mix). Very unlikely that resveratrol can substitute for lipoic acid, since the later sources a coenzyme.

Yes, 5 mg of elemental lithium. I used to try to quarter the pills to get 1.25 mg/day but they shatter too easily. Lithium's half-life is short (1-3 days) so I don't think it could be an intermittent supplement.

I get more than enough magnesium from diet and the butyrate supplement. Is there any evidence to support exceeding 500 mg/day? (I'm actually getting more than 500. I discounted the nut and oat magnesium some to account for the phytate inhibition of absorption.)

Carnitine supplements are poorly absorbed (ALCAR is even worse) so you get the TMAO risk. I'll settle for what I get from meat and endogenous synthesis until we have more information.

RNA would provide nucleic acids and ribose to fuel cancer proliferation.

Supplemental lipoic acid is for Nrf2, PGC-1alpha, AMPK, etc. which resveratrol also does. Lipoic acid does not seem to stick around in the body to make a coenzyme. Giving 1 mg to humans resulted in 91-99% urinated out within 24 hours. Furthermore, supplemental lipoic acid could not substitute for knocked-out endogeneous synthesis in mouse embryonic development. "The early embryonic death of Lias^−/− mice that we observe suggests that free LA cannot be used to form the lipoic acid moiety of E2-containing enzyme complexes or that LA cannot be transported into mitochondria in mice even though it can probably pass through the placenta."

In ATBC, prostate cancer risk was lowest for those who got the low-dose vitamin E (50 mg) and had the highest baseline vitamin E and gamma E intake. 100 microM of vitamins C or E don't interfere with Nrf2 the way NAC and GSH do, and I'm taking less than the amount required to get to 100 microM of either, so I don't think I'm taking much of a hit to hormesis.

Lipoic acid and carnitine are absorbed, and quite beneficially. See PMID 11854487 & 20370498.

By the same logic that stops you taking RNA you should swear off folate. But that wouldn't be a brilliant idea, would it? In fact it would be really dumb. See PMID 9758570. So you need to rethink your ideas about starving cancer of nutrients. Long term it doesn't work.

[krillin]

Hi Krillin,

What are your thoughts, in a nutshell, on

- melatonin

- aspirin

- so-called bioactive forms of folate

(some things you don't take)

 

I wrote some posts on melatonin here. Here are some papers on the hazards of melatonin's anti-dopamine effect. 1 2 3 4 5 6 It's also interesting how looking at something blue can relieve Parkinson's symptoms. Blue light suppresses melatonin release, so it could be involved.

 

I use willow bark instead of aspirin in an attempt to get cancer prevention without the platelet-killing COX-1 acetylation.

 

Reduced folates are definitely better than standard folic acid, but I don't think I need any more than what I get through diet and the 100 mcg of standard folic acid in the B-complex. I am a bit ambivalent about my folate target. This paper finds an optimum at 18-23 nM (estimated 400-475 mcg/day from NHANES III 1 2), and pancreatic cancer is lowest with 15-20 nM (estimated 348-430 mcg/day). But for dementia prevention >30 nM or > 523 mcg/day was best. (Although looking at the NHANES III data 30 nM is estimated to be 571 mcg/day.)

[krillin]

 

Lipoic acid and carnitine are absorbed, and quite beneficially. See PMID 11854487 & 20370498.

By the same logic that stops you taking RNA you should swear off folate. But that wouldn't be a brilliant idea, would it? In fact it would be really dumb. See PMID 9758570. So you need to rethink your ideas about starving cancer of nutrients. Long term it doesn't work.

 

I believe that lipoic acid was just used to upregulate antioxidants to deal with the carnitine overdose. Resveratrol can do that too. My concern with carnitine is that most of it isn't absorbed, so it can reach the gut flora and be converted to TMAO. We have other mitochondrial supplements so I don't think it's worth the risk.

 

For the people in the Nurses’ Health Study who didn't have a family history of colon cancer, folate didn't have much of an effect.

 

 

[blood]

Regarding krillin's regime...

 

I have a question for you, Timar.

 

You are notorious in this little community for what I'd describe as your "pro calorie" stance.

 

(Maybe I'm imagining things... I have a recollection of you advocating consumption of hamburgers/hotdogs at social gatherings so as to avoid feelings of 'social exclusion').

 

Therefore, I'm interested to hear your thoughts on the 'mini-fast' aspects of this anti-dementia protocol.

Edited by blood, 13 October 2014 - 03:16 AM.

[krillin]

I'm not currently taking curcumin because I'm waiting for Novasol to hit the market. Its bioavailability is so high that 500 mg yields 3.2 microM in the blood, which is mTOR-inhibiting so I'll probably do 2 weeks on, 2 weeks off like in the rapamycin studies.

 

Those guys cheated!

 

To each plasma or urine sample, 100 μL beta-glucuronidase type H-1 from Helix pomatia (3 mg/100 μL in 0.1 M sodium acetate buffer; Sigma-Aldrich Chemie GmbH, Schnelldorf, Germany) were added and samples incubated at 37°C for 45 min.

 

One must assume that they're concealing extensive conjugation happening to their curcumin. So it looks like we're stuck with having to shell out a fortune just to reach 0.1 microM with a handful of pills from Longvida or BCM-95.

[Michael Price]

Lipoic acid and carnitine are absorbed, and quite beneficially. See PMID 11854487 & 20370498.

By the same logic that stops you taking RNA you should swear off folate. But that wouldn't be a brilliant idea, would it? In fact it would be really dumb. See PMID 9758570. So you need to rethink your ideas about starving cancer of nutrients. Long term it doesn't work.

I believe that lipoic acid was just used to upregulate antioxidants to deal with the carnitine overdose. Resveratrol can do that too. My concern with carnitine is that most of it isn't absorbed, so it can reach the gut flora and be converted to TMAO. We have other mitochondrial supplements so I don't think it's worth the risk.

For the people in the Nurses’ Health Study who didn't have a family history of colon cancer, folate didn't have much of an effect.

What a load of rubbish. The five-fold reduction of colon cancer found in the nurses study was precisely in those women who took folate supplements for more than 5 years. The data you quote excluded those users.

[timar]

I have a question for you, Timar.

 

You are notorious in this little community for what I'd describe as your "pro calorie" stance.

 

(Maybe I'm imagining things... I have a recollection of you advocating consumption of hamburgers/hotdogs at social gatherings so as to avoid feelings of 'social exclusion').

 

Therefore, I'm interested to hear your thoughts on the 'mini-fast' aspects of this anti-dementia protocol.

 

 

This is becoming a running gag, right?

 

IIRC, I paraphrased a passage of Andrew Weil's book Eating Well for Optimum Health. He gave that example of a special occasion of feasting to counter a onesided perspective on eating, constricted to the biochemistry of nutrition and ignoring its various psychological and cultural aspects. I very much agree with his holistic approach. The antitheses of feasting and fasting a deeply rooted in human psyche and culture. It is perfectly fine and healthy to participate in an occasional feast, even if that involves eating unhealthy food.

 

In Germany it is a custom to eat jam-filled doughnuts on New Year's Eve. One of the doughnuts is traditionally filled with mustard instead of jam and the one who catches it is said to have a lucky new year. What do you think would be more supportive to your health, participating in the ritual by eating an odd doughnut or isolating yourself, being affraid of eating junk-food? I firmly believe that following an overly rigid diet often causes more harm than benefit, because the stress resulting from social isolation is actually worse than the harm of occasionally eating some junk. Moreover, demonization and obsession are two sides of the same psychological coin. If you want to make sure that your childred become addicted to sweets - tell them they are the Devil's poo and forbid them to have any sweets, ever. Allow them, however, to have some on occasion while teaching them how to eat a healthy and delicious diet and they likely will resist their addictive potential. The same is true for adults. Most people I talk to, who are overweight and crave junk-food, skip actually back and forth between indulgance and prohibition. The most effective way to break this viscious cycle of negative self-affirmation is a simple linguistic reprogramming, to change the "I must not eat that" to "I may eat it if I really want to, but I don't need it right now". When there is no negative feeling of guilt, there is no need to compensate it with further indulgance.

 

Anyway, the problem is not feasting, not even that it involves gorging on unhealthy food, but that in that all-American consumerist culture, feasting has become the default state. In a culture of collective ADHD and obesity, bombarding us with incentives to consume and consume ever more, we are constantly overstimulated, exceeding our capacity to absorb information as well as calories - junk-information and junk-calories, that is. Traditional cultures maintained a vital balance between the poles of feasting and fasting, being supportive not only to physical but also to emotional health, which has been completely thrown out of balance by modern consumerism.

 

So yes, fasting is crucial of a healthy lifestyle neglected in contemporary culture. As we have sadly lost the collective occasions for fasting, usually rooted in religious motives, whe have to rely on an individual incentive to compensate for our cultural shortcomings. The good thing is that today we have different variations upon the theme of fasting to choose from - anything between skipping a single meal (e.g. dinner-canceling) and eating a severely caloric-restricted diet for a period of months. I sometimes skip a meal or do a day of intermittent fasting.

 

Given all we know about the metabolic effect of fasting, I think that the 12 hour fast may be a crucial part of Bredesen's protocol.
 

Edited by timar, 13 October 2014 - 10:09 AM.

[Kevnzworld]

[quote name="Michael Price" post="692701" timestamp="1413179189"]

[quote name="krillin" post="692674" timestamp="1413163688"][quote name="Michael Price" post="692532" timestamp="1413086698"]

For the people in the Nurses’ Health Study who didn't have a family history of colon cancer, folate didn't have much of an effect.[/quote]
What a load of rubbish. The five-fold reduction of colon cancer found in the nurses study was precisely in those women who took folate supplements for more than 5 years. The data you quote excluded those users.[/quote]

I think it's important to differentiate between folic acid the form of folate that is added to fortify foods and natural folate, 5 methyl folate when discussing colon cancer risk.

[Michael Price]

[quote name="Kevnzworld" post="692776" timestamp="1413212004"]

[quote name="Michael Price" post="692701" timestamp="1413179189"]

[quote name="krillin" post="692674" timestamp="1413163688"][quote name="Michael Price" post="692532" timestamp="1413086698"]

For the people in the Nurses’ Health Study who didn't have a family history of colon cancer, folate didn't have much of an effect.[/quote]
What a load of rubbish. The five-fold reduction of colon cancer found in the nurses study was precisely in those women who took folate supplements for more than 5 years. The data you quote excluded those users.[/quote]

I think it's important to differentiate between folic acid the form of folate that is added to fortify foods and natural folate, 5 methyl folate when discussing colon cancer risk.[/quote]

I doubt that it is very imoortant, given that the body converts the differnt folates into each other. Anyway, it is not relevant to the above.

Edited by Michael Price, 13 October 2014 - 03:02 PM.

[krillin]

 

 

Lipoic acid and carnitine are absorbed, and quite beneficially. See PMID 11854487 & 20370498.

By the same logic that stops you taking RNA you should swear off folate. But that wouldn't be a brilliant idea, would it? In fact it would be really dumb. See PMID 9758570. So you need to rethink your ideas about starving cancer of nutrients. Long term it doesn't work.

I believe that lipoic acid was just used to upregulate antioxidants to deal with the carnitine overdose. Resveratrol can do that too. My concern with carnitine is that most of it isn't absorbed, so it can reach the gut flora and be converted to TMAO. We have other mitochondrial supplements so I don't think it's worth the risk.

For the people in the Nurses’ Health Study who didn't have a family history of colon cancer, folate didn't have much of an effect.

What a load of rubbish. The five-fold reduction of colon cancer found in the nurses study was precisely in those women who took folate supplements for more than 5 years. The data you quote excluded those users.

 

 

That is only true of Figure 1b, which looked at food sources only. For Figure 1a (total folate), the paper does not say that long-term supplement users were excluded, and it looks almost the same as the curve in 1b.

 

EPIC confirms the lack of effect. There is a hint (insignificant, however) that at higher folate concentrations, you get lower risk if you also have the C->T MTHFR polymorphism which inhibits folate methylation. And there's also a hint that at low folate concentrations you do better without the C->T.

 

[krillin]

I think it's important to differentiate between folic acid the form of folate that is added to fortify foods and natural folate, 5 methyl folate when discussing colon cancer risk.

I doubt that it is very imoortant, given that the body converts the differnt folates into each other. Anyway, it is not relevant to the above.

DHF reductase is pretty slow, so you can get unmetabolized folic acid in the bloodsteam for doses higher than 200 mcg of the standard stuff.

[Michael Price]

Lipoic acid and carnitine are absorbed, and quite beneficially. See PMID 11854487 & 20370498.

By the same logic that stops you taking RNA you should swear off folate. But that wouldn't be a brilliant idea, would it? In fact it would be really dumb. See PMID 9758570. So you need to rethink your ideas about starving cancer of nutrients. Long term it doesn't work.

I believe that lipoic acid was just used to upregulate antioxidants to deal with the carnitine overdose. Resveratrol can do that too. My concern with carnitine is that most of it isn't absorbed, so it can reach the gut flora and be converted to TMAO. We have other mitochondrial supplements so I don't think it's worth the risk.

For the people in the Nurses’ Health Study who didn't have a family history of colon cancer, folate didn't have much of an effect.

What a load of rubbish. The five-fold reduction of colon cancer found in the nurses study was precisely in those women who took folate supplements for more than 5 years. The data you quote excluded those users.

That is only true of Figure 1b, which looked at food sources only. For Figure 1a (total folate), the paper does not say that long-term supplement users were excluded, and it looks almost the same as the curve in 1b.

EPIC confirms the lack of effect. There is a hint (insignificant, however) that at higher folate concentrations, you get lower risk if you also have the C->T MTHFR polymorphism which inhibits folate methylation. And there's also a hint that at low folate concentrations you do better without the C->T.

By long-term user the later study you cited means anyone with >5 years folate supplementation. However, as the earlier follow-up study I cited pointed out, the reduction in cancer only became significant (and dramatic) for >15 years supplementation. So the earlier follow-up result stands : 5 fold reduction in colon cancer for long term (>15 years) high folate supplememntation. Your strategy of long-term cancer starvation diet is counter productive and actually pro cancer.

[Michael Price]

I think it's important to differentiate between folic acid the form of folate that is added to fortify foods and natural folate, 5 methyl folate when discussing colon cancer risk.

I doubt that it is very important, given that the body converts the differnt folates into each other. Anyway, it is not relevant to the above.

DHF reductase is pretty slow, so you can get unmetabolized folic acid in the bloodsteam for doses higher than 200 mcg of the standard stuff.

Since cancer rates /were/ reduced with long term folate supplementation it evidently is not important. Wood for the trees, guys.

[krillin]

Unmetabolized folic acid impairs natural killer cells. Partially-metabolized folic acid (DHF) acts as a folate antagonist. In NHANES III, folate didn't have much of an effect overall, but in supplement users higher folate increased risk (see Table 2). In pancreatic cancer, a recurring theme is that RDA-ish dietary folate is best (going above 20 nM is hazardous) but folic acid supplements don't work: HPFS & NHS PLCO Sweden.

 

Something more analogous to RNA supplements than folate would be the polyamines putrescine, spermidine, and spermine. Above-median intake was associated with 39% increased risk of colorectal adenoma.

 

 

[Michael Price]

Unmetabolized folic acid impairs natural killer cells. Partially-metabolized folic acid (DHF) acts as a folate antagonist. In NHANES III, folate didn't have much of an effect overall, but in supplement users higher folate increased risk (see Table 2). In pancreatic cancer, a recurring theme is that RDA-ish dietary folate is best (going above 20 nM is hazardous) but folic acid supplements don't work: HPFS & NHS PLCO Sweden.

Something more analogous to RNA supplements than folate would be the polyamines putrescine, spermidine, and spermine. Above-median intake was associated with 39% increased risk of colorectal adenoma.

No surprise there. If you have cancer then a cancer starvation diet might be wise, but I prefer to /prevent/ cancer in the first place. Long term, mean lifespan was increased with high folate and RNA,
<http://www.disease-t...ad.php?t=65403>

[blood]

... it is perfectly fine and healthy to participate in an occasional feast, even if that involves eating unhealthy food... What do you think would be more supportive to your health, participating in the ritual by eating an odd doughnut or isolating yourself, being affraid of eating junk-food? I firmly believe that following an overly rigid diet often causes more harm than benefit, because the stress resulting from social isolation is actually worse than the harm of occasionally eating some junk...

 

Where does it stop? Do you eat a cookie every day at work, because that is what your colleagues do? Define occasionally.

 

What you're saying sounds like common sense, but I tend to think that unquestioned (common sense) assumptions are often the enemy of good science & the search for truth. Is it really true that saying no to the jam doughnut will invariably result in an individual feeling socially isolated (so severely isolated, that the individual will suffer adverse health consequences)? These ideas are testable, and should be tested, really, not just promoted and uncritically accepted.

 

Skills associated with psychological independence are an important strength. Saying no to a drink or drug, when we have to drive (for example). Why is consumption of toxic calories any different?

 

That's my opinion, anyway.

 

I do appreciate very much the intelligence, breadth & depth of knowledge, & passion you bring to your posts on Longecity, Timar. I am curious - are you studying or researching some aspect of nutrition?

Edited by blood, 15 October 2014 - 12:01 PM.

[krillin]

 

Unmetabolized folic acid impairs natural killer cells. Partially-metabolized folic acid (DHF) acts as a folate antagonist. In NHANES III, folate didn't have much of an effect overall, but in supplement users higher folate increased risk (see Table 2). In pancreatic cancer, a recurring theme is that RDA-ish dietary folate is best (going above 20 nM is hazardous) but folic acid supplements don't work: HPFS & NHS PLCO Sweden.

Something more analogous to RNA supplements than folate would be the polyamines putrescine, spermidine, and spermine. Above-median intake was associated with 39% increased risk of colorectal adenoma.

No surprise there. If you have cancer then a cancer starvation diet might be wise, but I prefer to /prevent/ cancer in the first place. Long term, mean lifespan was increased with high folate and RNA,
<http://www.disease-t...ad.php?t=65403>

 

 

Is there any epidemiology to help find the sweet spot on RNA's U-curve? All I could find is that diets completely purified of nucleotides impair the immune system.

 

I found another U-curve for folate: rectal cancer was lowest for 298-347 mcg. (For colon cancer the curve looks flat until 419 mcg when risk goes up. In Table 3 where they do a combined model for all nutrients, folate has the same sweet spot regarding rectal cancer, but for colon cancer, risk becomes lowest below 297 mcg.) Other benefical nutrients were B6 (>3.4 mg), B12 (>11.1 mcg), Se (119-145 mcg), E (>7.1 mg), and C (>198 mg).

 

This made me wonder if they controlled for everything in the Nurses' Health Study where they assumed that folic acid was the effective ingredient in the multivitamins. It looks like B6, B12, and Se were not considered. A multivitamin with 2 mg B6, 6 mcg B12, and 55 mcg selenium would bump an RDA-ish diet into the optimal quintiles, so it's possible that these three were responsible for the multivitamin benefit and the multivitamin folic acid may have been as unimpressive as dietary folate for those without a family history.
 

[Michael Price]

Unmetabolized folic acid impairs natural killer cells. Partially-metabolized folic acid (DHF) acts as a folate antagonist. In NHANES III, folate didn't have much of an effect overall, but in supplement users higher folate increased risk (see Table 2). In pancreatic cancer, a recurring theme is that RDA-ish dietary folate is best (going above 20 nM is hazardous) but folic acid supplements don't work: HPFS & NHS PLCO Sweden.

Something more analogous to RNA supplements than folate would be the polyamines putrescine, spermidine, and spermine. Above-median intake was associated with 39% increased risk of colorectal adenoma.

No surprise there. If you have cancer then a cancer starvation diet might be wise, but I prefer to /prevent/ cancer in the first place. Long term, mean lifespan was increased with high folate and RNA,
<http://www.disease-t...ad.php?t=65403>

Is there any epidemiology to help find the sweet spot on RNA's U-curve? All I could find is that diets completely purified of nucleotides impair the immune system.

I found another U-curve for folate: rectal cancer was lowest for 298-347 mcg. (For colon cancer the curve looks flat until 419 mcg when risk goes up. In Table 3 where they do a combined model for all nutrients, folate has the same sweet spot regarding rectal cancer, but for colon cancer, risk becomes lowest below 297 mcg.) Other benefical nutrients were B6 (>3.4 mg), B12 (>11.1 mcg), Se (119-145 mcg), E (>7.1 mg), and C (>198 mg).

This made me wonder if they controlled for everything in the Nurses' Health Study where they assumed that folic acid was the effective ingredient in the multivitamins. It looks like B6, B12, and Se were not considered. A multivitamin with 2 mg B6, 6 mcg B12, and 55 mcg selenium would bump an RDA-ish diet into the optimal quintiles, so it's possible that these three were responsible for the multivitamin benefit and the multivitamin folic acid may have been as unimpressive as dietary folate for those without a family history.

o
The study you cite did not reach significance for high dose folate downside. (It reached significance for B6 and B12, and was uniformly positive re high doses.) The optimum folate dose on some measures (e.g. liver morphology) may be very high <http://www.ncbi.nlm....bmed/15113958>.

The nurses study admitted that the cancer protective effect may have been due to vitamin D. Personally I doubt that, since vitamin D protection starts to kick in pretty much immediately, rather than after 15 years.

Edited by Michael Price, 16 October 2014 - 10:08 AM.

[krillin]

 

 

I found another U-curve for folate: rectal cancer was lowest for 298-347 mcg. (For colon cancer the curve looks flat until 419 mcg when risk goes up. In Table 3 where they do a combined model for all nutrients, folate has the same sweet spot regarding rectal cancer, but for colon cancer, risk becomes lowest below 297 mcg.) Other benefical nutrients were B6 (>3.4 mg), B12 (>11.1 mcg), Se (119-145 mcg), E (>7.1 mg), and C (>198 mg).

The study you cite did not reach significance for high dose folate downside. (It reached significance for B6 and B12, and was uniformly positive re high doses.) The optimum folate dose on some measures (e.g. liver morphology) may be very high <http://www.ncbi.nlm....bmed/15113958>.

When they did the combined model in Table 3 the downside of high dose folate was significant for both colon and rectal.

 

It's interesting that liver rejuvenation only took 4 weeks. That suggests that cycling something briefly would allow necessary maintenance to occur without having to also feed cancer continuously. Folate has too long a half-life to be cycled, so perhaps RNA or leucine would do the same trick.

[Michael Price]

I found another U-curve for folate: rectal cancer was lowest for 298-347 mcg. (For colon cancer the curve looks flat until 419 mcg when risk goes up. In Table 3 where they do a combined model for all nutrients, folate has the same sweet spot regarding rectal cancer, but for colon cancer, risk becomes lowest below 297 mcg.) Other benefical nutrients were B6 (>3.4 mg), B12 (>11.1 mcg), Se (119-145 mcg), E (>7.1 mg), and C (>198 mg).

The study you cite did not reach significance for high dose folate downside. (It reached significance for B6 and B12, and was uniformly positive re high doses.) The optimum folate dose on some measures (e.g. liver morphology) may be very high <http://www.ncbi.nlm....bmed/15113958>.

When they did the combined model in Table 3 the downside of high dose folate was significant for both colon and rectal.

It's interesting that liver rejuvenation only took 4 weeks. That suggests that cycling something briefly would allow necessary maintenance to occur without having to also feed cancer continuously. Folate has too long a half-life to be cycled, so perhaps RNA or leucine would do the same trick.

True, I missed the table 3 result. I place greater weight on the nurses study, though, since they specifically looked at supplements in healthy people and at long term effects - and had a much larger population base.
I'm not a big fan of cycling. I prefer to give the body time to adjust to dietary intakes, and not continuously vary things.

[albedo]

Good information on colon/rectal cancer. Have you guys a take on increased prostate cancer risks. I understand also in this respect you need to distinguish folic acic and 5 methylfolate. Thank you.

 

PS

Also recommend to see the discussion here: http://www.longecity...ick-to-the-rda/

[Michael Price]

Good information on colon/rectal cancer. Have you guys a take on increased prostate cancer risks. I understand also in this respect you need to distinguish folic acic and 5 methylfolate. Thank you.

PS
Also recommend to see the discussion here: http://www.longecity...ick-to-the-rda/

Thanks for the thread pointer. Looks like a rehash of the discusssion here. Krillin put it nicely back in 2008 when he said "The prospective cohort studies say you need to take it for at least 15 years before you benefit. The study Michael [Rae] linked to closed up shop after 6-8 years and used people who were already growing polyps, which tells me that the study was cunningly designed to set up folate to fail. "
Re prostate cancer, the same caveats apply: folate will speed up existing tumour growth while preventing long term cancer incidence, although less so than for colon cancer. For prostate prevention selenium looks very good, and also lycopene, saw palmetto, boron, zinc plus supplements in general for broad combo protection.

[albedo]

 

Good information on colon/rectal cancer. Have you guys a take on increased prostate cancer risks. I understand also in this respect you need to distinguish folic acic and 5 methylfolate. Thank you.

PS
Also recommend to see the discussion here: http://www.longecity...ick-to-the-rda/

Thanks for the thread pointer. Looks like a rehash of the discusssion here. Krillin put it nicely back in 2008 when he said "The prospective cohort studies say you need to take it for at least 15 years before you benefit. The study Michael [Rae] linked to closed up shop after 6-8 years and used people who were already growing polyps, which tells me that the study was cunningly designed to set up folate to fail. "
Re prostate cancer, the same caveats apply: folate will speed up existing tumour growth while preventing long term cancer incidence, although less so than for colon cancer. For prostate prevention selenium looks very good, and also lycopene, saw palmetto, boron, zinc plus supplements in general for broad combo protection.

 

 

Thank you. A point which is worth considering is we all have pre-cancereus or cancer cells and while immune system and regulatory mechanisms keep them at bay we should try and not disrupt them. Can that be an explication of U curves we see for some nutrients? I guess the same applies to other than folic acid nutrients, e.g. benfotiamine etc ...

 

Edited by albedo, 17 October 2014 - 11:28 AM.

[Michael Price]

Good information on colon/rectal cancer. Have you guys a take on increased prostate cancer risks. I understand also in this respect you need to distinguish folic acic and 5 methylfolate. Thank you.

PS
Also recommend to see the discussion here: http://www.longecity...ick-to-the-rda/

Thanks for the thread pointer. Looks like a rehash of the discusssion here. Krillin put it nicely back in 2008 when he said "The prospective cohort studies say you need to take it for at least 15 years before you benefit. The study Michael [Rae] linked to closed up shop after 6-8 years and used people who were already growing polyps, which tells me that the study was cunningly designed to set up folate to fail. "
Re prostate cancer, the same caveats apply: folate will speed up existing tumour growth while preventing long term cancer incidence, although less so than for colon cancer. For prostate prevention selenium looks very good, and also lycopene, saw palmetto, boron, zinc plus supplements in general for broad combo protection.

Thank you. A point which is worth considering is we all have pre-cancereus or cancer cells and while immune system and regulatory mechanisms keep them at bay we should try and not disrupt them. Can that be an explication of U curves we see for some nutrients? I guess the same applies to other than folic acid nutrients, e.g. benfotiamine etc ...

A fully cancerous cell is the end point of a series of mutations, with prevention aimed at slowing the acquisition of such mutations, or repairing early stage DNA damage where possible. Supplements in general are good at prevention. Once tumourigenesis stage is reached then we are in different ball park game. This is particularly relevant for prostate cancer, since most men have prostate tumours by mid-40s, and the strategy has to be more targeted. Saw palmetto and lycopene are my personal guardians in this respect.

[albedo]

...This is particularly relevant for prostate cancer, since most men have prostate tumours by mid-40s, and the strategy has to be more targeted. Saw palmetto and lycopene are my personal guardians in this respect.

 

 

Thank you. Maybe a bit off topics here .... just to tell I agree. I am supplementing with the usual prostate supplement suspects since many years (here to be specific, sorry for the LEF marketing, not intentional, just wish to list the nutrients, but I do trust the Company). Include anti-inflammation nutrients (e.g. tumeric/curcumin, Zyflamend, ..). It is very common to have some inflammation in the prostate which we need to fight as the death! Here is my small story in this regard...

 

[krillin]

 

Good information on colon/rectal cancer. Have you guys a take on increased prostate cancer risks. I understand also in this respect you need to distinguish folic acic and 5 methylfolate. Thank you.

PS
Also recommend to see the discussion here: http://www.longecity...ick-to-the-rda/

Thanks for the thread pointer. Looks like a rehash of the discusssion here. Krillin put it nicely back in 2008 when he said "The prospective cohort studies say you need to take it for at least 15 years before you benefit. The study Michael [Rae] linked to closed up shop after 6-8 years and used people who were already growing polyps, which tells me that the study was cunningly designed to set up folate to fail. "
Re prostate cancer, the same caveats apply: folate will speed up existing tumour growth while preventing long term cancer incidence, although less so than for colon cancer. For prostate prevention selenium looks very good, and also lycopene, saw palmetto, boron, zinc plus supplements in general for broad combo protection.

 

I was in denial back then, and also hadn't found all those U-curves yet. I also used to take beta carotene, 800 IU alpha tocopherol, copper, manganese, and strontium.

 

I haven't found a U-curve for prostate cancer, which is understandable since it's relatively slow-growing. This study found natural folate and synthetic folic acid fortification to be beneficial, while supplements didn't help. (Natural folate was also better than all synthetics for reducing high-grade prostate cancer risk.) This is consistent with what I posted earlier about the body being able to metabolize small doses of the synthetic but choking on supplement amounts. So you have to ignore the total folate data for dose determination since it includes supplements. Optimum is therefore >669 mcg dietary folate equivalent (natural folate + 1.7*folic acid fortification), and within that total there should be >346 mcg natural folate. Prostate cancer is in my family history, so I'm going to eat crow and increase my dose to that level. I'll be cautious and assume that lemon peel folate supplements fall into the 1.7x category like synthetic folic acid and 5-methyl folate do.

 

Zinc is probably best as citrate.