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Recent Comments


Recent Comments


pamojja
Sep 14 2017 09:37 PM
Multi- Vitamin and Mineral stack

I'm still searching, but I doubt there is any research of A, D3 and K2 in combination with hard health outcomes yet. Only have my own anecdotal case of being plagued with a number of devastating chronic diseases, and without much to loose, therefore was more than willing to experiment while monitoring. I didn't regret.

 

However, you might be absolutely right in that the A:D ratio which worked for me, might turn out completely off in a healthy person. Therefore always worthwhile testing serum retinol and retinol binding protein for confirmation. As an example of a very healthy person, what kind of serum levels you get with A and D?


Michael
Sep 14 2017 09:22 PM
Multi- Vitamin and Mineral stack

In principle, I'd agree that we'd want to be able to evaluate the whole system working together — but I don't know of any proper data on the subject, even in animals. The studies cited in the posts that you and RWhigham link cite are biochemistry, acute toxicity, and rather speculative inductions (eg, that the reason why trials conducted in the 1930s showed that cod liver oil reduced incidence of common colds and respiratory infections but that a 2004 trial yielded mixed results is that the cod liver oils differed in A and D content, and should have had higher D and lower A than the 2004 trial — or that the reason for low 25(OH)D3 in LEF members is excessive vitamin A supplementation from non-LEF multivitamins, even though the article itself says that "Most Foundation members take the Two-Per-Day or Life Extension Mix multi-nutrient formulas," which by their notions of a correct vitamin A dose do not suffer this problem).

 

Are either of you aware of any long-term studies in otherwise-normal, aging mammals testing the effects of different ratios of vitamins A, D3, and K2 against hard health outcomes?


pamojja
Sep 14 2017 08:26 PM
Multi- Vitamin and Mineral stack

Thanks for both comments, only saw them now.

 

I'm thinking more in line with Chris Masterjohn. And got his ideas confirmed through vitamin A and D serum testing, while aiming at the middle of normal ranges. In that I actually need at least a A to D IU ratio of 2 to 1 (the opposite RWhigham suggests). With the higher intake of preformed vitamin A, always slowly titrating and measuring, also infrequent psoriasis outbreaks have ceased (above 24.000 IU/d). But everyone is different, where only individual testing counts.

 

The problem I have with all the references you both provide, is that they look completely unrealistically at one vitamin - A or D in isolation only. That's how I never would even think of them, or further excluding vitamin K2 in all their synergistic effects.


aribadabar
Sep 08 2017 06:37 PM

Michael
Sep 08 2017 04:07 AM
Prevent Early Mortality

To make meaningful comments, we'd have to understand why you were taking these things, and at the dose you're taking them. I see no justification at all for an otherwise-healthy aging person  to be taking Olive Leaf Extract, Ashwangandha, or Curcumin. EGCG, Broccoli Sprout Extract, and Garlic Extract are fine, I suppose, but you'd be better taking the actual foods (and green tea pills have been linked to a fair number of cases of liver toxicity, unlike the tea). Your EPA+DHA dose is probably twice as high as it should be. Your vitamin D is also likely way too high: are you having your 25(OH)D tested, and if so, what level are you targeting? See discussion at my stack (and, indeed, see discussion there on supplementation generally).


Michael
Sep 06 2017 09:30 PM
Michael's "Tiered" Supplement

In response to aribadabar's questions:
 
I quit IP6 because I have persistently high serum phosphorus (which is bad), and because my dietary IP6/phytate and inositol is already likely at the extreme end of the population (legumes and nuts). Additionally, there was little positive reason to take it, either: I don't have any history of kidney stones, I drink plenty of fluids and have a high-intrinsic-water diet, and no one has yet done a study showing it benefits otherwise-healthy aging rodents or humans. And if it's working by mobilizing NK cells, well, who knows what decades of incessant NK stimulation could do?
 
I quit the lactoferrin because I finally admitted to myself that there's never really been any good reason to take the stuff. And my iron stores are still right where I want them to be.
 
Glycine: I decided that I had to stop drinking water just before bed in order to avoid a mid-night trip to the bathroom, which seems like a more sensible way to ensure solid slip than doping myself up with supplements — and I'm reluctant to take it on an empty stomach. Plus, I suspect that it may have been the reason for my occasional bouts of waking up at 3 AM with a pounding heart and a sweat: my hypothesis is that this is due to Somogyi effect, arising from the interaction of glycine-induced insulin secretion with my having CR-associated high insulin sensitivity and low glycogen stores: see here and here. Certainly, I've had none of these episodes in the months since I quit taking it.


Michael
Sep 06 2017 09:19 PM
Michael's "Tiered" Supplement

 

The diff' is that PC raises TMAO less than citicoline.

Do we know whether it raises TMAO less per total mg or per mg of choline supplied? 

 

Per mole (properly) of choline  supplied. We don't have actual quantification on citicoline, but it's been demonstrated that it raises it, and since citicoline is hydrolyzed in the intestine prior to absorption, the relative amount should be similar to that of choline salts; clean PC barely raises TMA(O) at all, whereas choline salts raise it ninefold.


Gordo
Sep 06 2017 05:01 PM
Life Extension and Great Health Regimen Stack

Decent holistic reasoning, but while Jiaogulan has ben shown to improve insulin sensitivity and reduce HbA1c, it doesn't have any evidence for it's longevity effects. You could pick something like rapamycin, selegiline, metformin, or aspirin for more assured increases in lifespan. I'd even pick reishi, another 'immortality herb' over jiaogulan, but ideally both need to be studied more... I hope we can secure some funding for such research in the near future!

Turmeric + Black Pepper is probably not doing much for you, considering you have a plant-based diet already. The clinically meaninful effects are seen with high doses of mixed curcuminoids, not plain turmeric.

Otherwise... good approach!

 

OK, let me take these one at a time.  First with regard to mushrooms, I agree, which is why I specifically mentioned them in my write up, although I could have gone into more detail.  Shiitake and Reishi are fine choices, I recommend a wide variety, and even the plain old cheap white button mushroom is very good for you.  Oyster mushrooms contain natural LDL lowering compounds.

 

With regard to jiaogulan - there are a large number of published studies from reputable sources demonstrating its health benefits, if you take that alone, its pretty logical to assume it would help with longevity, anecdotally, the people groups that consume it daily are known for their comparative longevity (admittedly, that alone is not great evidence).  Its very hard to scientifically prove ANYTHING is good for human longevity, we just know what improves biomarkers of health.  Mouse studies are interesting but not always relevant.  

 

"You could pick something like rapamycin, selegiline, metformin, or aspirin for more assured increases in lifespan"

 

I consider these myths, mostly debunked, although still under active scientific scrutiny. There is even less evidence that these will result in longevity than exists for jiaogulan, in fact taking these drugs is more likely to harm an otherwise healthy person. Rapamycin is well known for compromising the immune system and promoting cancer, metformin has an enormous list of negative side effects and has never been shown to increase max lifespans (more on this below).  Aspirin is a terrible idea for healthy people (primarily due to increased chance of gastrointestinal bleeding):Aspirin Bleeding Risks Outweigh Benefits - ABC News

 

 

"The following critique was authored by a Professor of Applied Statistics at the Open University in the UK ("Professor" is a much more senior position in the UK than the USA, denoting something like a department head), and seems cogent and consistent with a slightly cryptic phrase in the abstract, in which case teh study is likely not worth paying much attention to:
 

Quote

Expert reaction to study looking at type 2 diabetes, metformin and lifespan

 

The title of this paper itself is not helpful in that anyone reading it might get the wrong idea – this study cannot actually answer the question it poses (“Can people with type 2 diabetes live longer than those without?”) for reasons discussed below, and it sounds almost as if there are grounds to advise people without diabetes to take metformin. But in fact the study isn’t saying that at all.

In the press release, Craig Currie says “People lose on average around eight years from their life expectancy after developing diabetes” and goes on to explain why. So if the life expectancy of people with type 2 diabetes is so much shorter, how on earth can they “live longer than people without the disease”, as the title of the release and the paper both say?

The answer is that the comparison in the paper runs only over the time period when the patients with diabetes were on first-line treatment with metformin, on its own (and there’s a similar comparison involving patients whose first-line treatment is with sulphonylureas). At some point after this first-line treatment starts, many of the patients with diabetes would be switched from metformin alone onto a second-line treatment, and this switch is (or should be) necessary because the diabetes or its effects have got worse. But at that point the comparison in this study simply stops.

So the quote in the press release about an eight year reduction in life expectancy, in people who develop type 2 diabetes, is talking about the entire rest of a person’s life after the diagnosis, including the time when they might be on a more aggressive second-line treatment. But the comparison in the paper is looking only at the time before the treatment changes. ...

[MR: This is evidently what the abstract means by using a "censored followup:" they ONLY looked at deaths occurring WHILE the person was on metformin or sulfonylureas: if your disease progressed, and they added on a secnd drug to bring your glucose back under control, you were simply "censored" out of further followup. This would obviously greatly bias the resulting mortality rates (and note: it is for sure from the abstract that they did not actually look at life expectancy, despite the press release AND the title of the abstract: explicitly , they ONLY looked at mortality rates of people while they were only on one drug (or, during the matched number of years of the nondiabetic controls). This means, by definition, that people who were put on the drug most usually used for the mildest diabetes (metformin) and who remained stable and healthy on it, were being compared to more severe patients at outset (on sulfonylureas), and as soon as they got sick they vanished from the analysis! Comparing even average nondiabetic people to unusually successful diabetics is, from the get-go, comparing elite diabetics to merely average aging people. Returning to the critique:]

The researchers did match the controls with patients with diabetes in certain ways, and in their statistical analysis they try to allow statistically for other differences between the people with diabetes and the controls. But the paper itself points out some issues. The researchers could not take into account certain possible confounders (other variables that might affect the comparison) because they did not have data on them for enough of the controls. Even without that important issue, statistical adjustment for confounders is never perfect. The difference in survival between people with diabetes on metformin, and controls without diabetes, was statistically significant but in fact rather small, and probably within the range where it could be explained by residual confounding ...

Further, the paper itself also points out that people with diabetes are more likely be monitored for, and receive interventions for, problems with the heart and circulation. This extra intervention and monitoring, and the possibility of residual confounding, between them cast huge doubt on the possibility that the better survival in the patients taking metformin, compared to controls without diabetes, was simply because they were taking metformin. ...

http://www.scienceme...n-and-lifespan/

 

And, as a reminder: metformin has been tested now at high and low doses in normal, healthy mice, and also in a somewhat flawed study in rats, and in no case has metformin increased maximum lifespan;there was a very mild increase in average LS in the mouse studies, which might well be due to residual effects of a diet of lab chow and no exercise." [Credit to Michael Rae on that metformin info].

 

"Turmeric + Black Pepper is probably not doing much for you"

Like Jiogulan, there is a mountain of scientific evidence for the benefits of small amounts of turmeric in one's diet, among many other things, its a very powerful anti-inflamatory.  Slightly off topic, but its also a phenomenal tool for recovery improving postoperative pain and fatigue.

 

-Gordo


aribadabar
Sep 06 2017 04:42 AM
Michael's "Tiered" Supplement

Why did you remove Lactoferrin, Inositol /IP-6 and Glycine from your regimen as per its previous version?


Adam Karlovsky
Sep 06 2017 03:25 AM
Life Extension and Great Health Regimen Stack

Decent holistic reasoning, but while Jiaogulan has ben shown to improve insulin sensitivity and reduce HbA1c, it doesn't have any evidence for it's longevity effects. You could pick something like rapamycin, selegiline, metformin, or aspirin for more assured increases in lifespan. I'd even pick reishi, another 'immortality herb' over jiaogulan, but ideally both need to be studied more... I hope we can secure some funding for such research in the near future!

Turmeric + Black Pepper is probably not doing much for you, considering you have a plant-based diet already. The clinically meaninful effects are seen with high doses of mixed curcuminoids, not plain turmeric.

Otherwise... good approach!


Michael
Sep 04 2017 08:02 PM

jwilcox25
Sep 04 2017 02:52 AM
Michael's "Tiered" Supplement

The diff' is that PC raises TMAO less than citicoline. I don't know which would raise serum choline more, but I prefer PC because it's both safer based on TMAO and I think consuming it this way is more conservative: my far-from-expert understanding is that CDP-choline is quite rare in the diet, being only present as an intermediate in PC synthesis in the CDP-choline pathway.

Do we know whether it raises TMAO less per total mg or per mg of choline supplied?  


RWhigham
Sep 03 2017 10:29 PM
Multi- Vitamin and Mineral stack
high intake of preformed vitamin A increases fracture risk.

Ref: Excess Vitamin A Can Thwart Vitamin D

Osteoporosis is caused by a mismatch between vitamin A, D, and K2.  The ideal A/D ratio wt/wt is about 5 to 1 which corresponds to an iu/iu ratio of 1 to 2.4 since 1 mg of vitamin A is 3,333 iu and 1 mg of  vitamin D3 is 40,000 iu  so  5 g to 1 g  = (5)(3,333 iu)/40,000 iu =  1 to 2.4  iu/iu

 

Example:  vitamin A retinol at 1,000 iu per day needs 2,400 iu per day of D3.

 

The "more is better" supplements are ridiculous--a quick look a Amazon show "vitamin A" in 5,000 to 25,000 iu capsules (likely mostly beta-carotene).  A 25,000 iu dose of retinol would need to be balanced with 2.4 x 25,000 = 60,000 iu of D3.  Perhaps you could take one 25,000 iu vitamin A (as retinol) per month and balance it with 2,000 iu of vitamin D3 daily.


Michael
Sep 01 2017 06:14 PM
Multi- Vitamin and Mineral stack

A note of caution on preformed vitamin A. You're right that the acute toxicity of very high levels of retinol has possibly been overestimated, but there is significant evidence that high intake of preformed vitamin A increases fracture risk. The studies aren't totally consistent; notably, studies based on serum levels are far less likely to find an association, but that may be because serum retinyl esters poorly track high dietary intake. Even so, a meta-analysis of prospective studies concluded that both high dietary and high blood retinol are associated with elevated fracture risk.


HighDesertWizard
Sep 01 2017 02:52 PM
A Longevity Promoting Regimen Leveraging the CAP, established and double blind tested by Mother Nature...
i have been deliberately vague about some herbal supplements I now take by listing them as a single entry. Here's why...

They are important to the regimen because they inhibit NF-kB, but I have changed these just recently. I do not believe they are central to Muscarinic Acetylcholine Agonism and the point of my entry in the Regimen Content is to emphasize the value of M1 Muscarinic Acetylcholine Agonism.

It is M1 Muscarinic Acetylcholine Receptor Agonism that is central to the Inflammation Reduction, Longevity Promoting characteristics of my regimen and I don't want to obscure that fact...

HighDesertWizard
Sep 01 2017 06:15 AM
A Longevity Promoting Regimen Leveraging the CAP, established and double blind tested by Mother Nature...

I will add and subtract to and from the stack over time...

 

Here's a snapshot of my Teloyears report...

 

UAa5x3Qh.jpg


Michael
Aug 31 2017 09:23 PM
Michael's "Tiered" Supplement

The diff' is that PC raises TMAO less than citicoline. I don't know which would raise serum choline more, but I prefer PC because it's both safer based on TMAO and I think consuming it this way is more conservative: my far-from-expert understanding is that CDP-choline is quite rare in the diet, being only present as an intermediate in PC synthesis in the CDP-choline pathway.


pamojja
Aug 30 2017 08:00 PM
PAD and additional Remissions
And at the beginning of the 6th year, though with in many respect worse lab results, intermittent claudication symptoms have completely gone for the first time during all these years.

 

...To summarize - through the synergistic effects of lifestyle modifications, nutrient and herbal extract supplementation it was possible: ...

 

Interestingly, right after the time intermittent claudication ceased I came across the work of Kelly A. Turner, which summarized pretty well for me in a different context the different realms of lifestyle-modifications possibly involved. Since my stack doesn't talks much beyond point 4 of this list - and supplements alone are definitely not enough against severe chronic conditions - I add her whole list here:

 

 


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During the course of the study, Kelly identified more than seventy-five factors that cancer survivors said they used as a part of their healing journey. Nine of these factors were used by almost every one of them. They are as follows:

 

1. Radically change the diet
Let your food be your medicine, and medicine your food (Hippocrates)
- avoid sugar, meat, dairy products and processed foods
- eat lots of fruits and vegetables
- limit to organic food
- drink only filtered water
 

2. Take control of health
Action is the basic key to success (Pablo Picasso)
- actively participate
- be prepared for change
- resolve resistance
 

3. Follow your own intuition
In vital matters, the decision should come from the unconscious, somewhere from within (Sigmund Freud)
- listen to body signals
- activate the intuition
- find the right change
 

4. Take herbs and food supplements
The art of healing comes from nature and not from the physician (Paracelsus)
- help digestion: digestive enzymes, prebiotics and probiotics
- boost the immune system: e.g. Vitamin C, other vitamins (B12, D3, K2), fish oil, trace elements, certain edible fungi, aloe vera; and hormones (melatonin)
- detoxify the body:
- antimycotics (eg olive leaf extract, celery, nettle)
- antiparasitic substances (eg wormwood, yellow root, black nut husks)
- antibacterial and antiviral (eg garlic, oregano oil, Pau d'Arco)
- liver detoxification (eg milk spotted dwarf, dandelion root, sweet tooth root)
- supplements alone is not enough
 

5. Release oppressed emotions
Anger is an acid which can cause much greater damage to the vessel in which it is stored than to what it pours (Mark Twain)
- disease is blockade
- what are suppressed emotions?
- stress and cancer
- anxiety and cancer
- the waterfall solution
 

6. Enhance positive emotions
The meaning of life is to be happy (Dalai Lama)
- what are positive emotions?
- what are the positive emotions in the body?
- happiness must be practiced daily
- but one does not have to be permanently happy
 

7. Allow social support
In poverty and misery, friends are the only refuge (Aristotle)
- experience love
- do not feel alone
- physical contact
 

8. Deepen the spiritual connection
This is the greatest mistake in the treatment of diseases: that there are doctors for the body and physicians for the soul, where both can not be separated (Plato)
- experience spirituality
- a third kind of love
- the relationship between the physical and the spiritual
- it is important to exercise regularly
- it is important to calm the mind
 

9. Have strong reasons for life
People say that it is the meaning of life that we all seek. I do not believe that this is what we are really looking for. I believe what we are looking for is an experience of being alive ... (Joseph Campbell)
- placing deep trust in one's inner being
- the mind directs the body
- find one's calling
 

http://www.radicalremission.com/

 

This April I finally quit one of my two part-time jobs, because it has become merely a stick it out feat, and below devastating effects didn't change even half an hour in working-ability or sleeping needs all these years:

 

 


jwilcox25
Aug 29 2017 06:10 PM
Michael's "Tiered" Supplement

What causes the difference in safety between taking the 2 x 420mg PC vs 2 x 55mg citicholine?  Would the two result in the same serum choline levels?


Nate-2004
Aug 28 2017 11:42 PM
Visible Aging Signs

Please note that if you only pick any one single thing off this list, pick the CeraVe and focus on good habits mentioned in the description.


Michael
Aug 24 2017 11:19 PM
Michael's "Tiered" Supplement

What brand of ubiquinol do you use Michael? No love for Mitoq?

 

I use any reputable brand: it's all Kaneka in the end.

 

No, no love for MitoQ. First, as I indicated, I'm taking it for physiological replacement, not some pharmacological mito antioxidant effect. Second, it would be foolish at this point to be taking it for some pharmacological mito antioxidant effect, since it's very clear at this point that it has none in normal mammals(1,2) — nor, indeed, is there any other evidence of any benefit in normal mammals, except maybe in skin cream.

 

References

1: Sakellariou GK, Pearson T, Lightfoot AP, Nye GA, Wells N, Giakoumaki II, Griffiths RD, McArdle A, Jackson MJ. Long-term administration of the mitochondria-targeted antioxidant mitoquinone mesylate fails to attenuate age-related oxidative damage or rescue the loss of muscle mass and function associated with aging of skeletal muscle. FASEB J. 2016 Nov;30(11):3771-3785. Epub 2016 Aug 22. PubMed PMID: 27550965; PubMed Central PMCID: PMC5067250.

2: Rodriguez-Cuenca S, Cochemé HM, Logan A, Abakumova I, Prime TA, Rose C, Vidal-Puig A, Smith AC, Rubinsztein DC, Fearnley IM, Jones BA, Pope S, Heales SJ, Lam BY, Neogi SG, McFarlane I, James AM, Smith RA, Murphy MP. Consequences of long-term oral administration of the mitochondria-targeted antioxidant MitoQ to wild-type mice. Free Radic Biol Med. 2010 Jan 1;48(1):161-72. doi: 10.1016/j.freeradbiomed.2009.10.039. Epub 2009 Oct 23. PubMed PMID: 19854266.


Michael
Aug 24 2017 04:05 AM
Thymus Rejuvenation

It's really not clear that oral arginine substantially increases growth hormone secretion, particularly in physically active people or in combination with exercise:
 

The Ergogenic Potential of Arginine
It is well documented that the infusion of arginine stimulated growth hormone secretion from the anterior pituitary [5, 7]. This increase in growth hormone secretion from arginine infusion has been attributed to the suppression of endogenous somatostatin secretion [8]. The amounts of arginine infused to elicit the growth hormone response ranged from 12 grams to 30 grams. The clinical investigations of oral consumption of arginine and its impact on growth hormone release are not in agreement. When arginine (1.2 g) was ingested along with the amino acid lysine (1.2 g) in young males, peak plasma growth hormone concentrations increased 8-fold at 90 minutes post-ingestion [9]. However, when arginine and lysine were ingested alone at the same doses, there was no corresponding increase in plasma growth hormone. Suminiski and associates [10] reported that the ingestion of arginine (1.5 g) and lysine (1.5 g) resulted in a 2.7-fold increase in plasma growth hormone concentrations in resistance trained males. Colombani et al. [11] supplemented marathon runners with 15 g arginine aspartate for 14 days before a marathon run. On the day of the marathon, blood samples were taken shortly before the run, after 31 km, at the end of the run, and after a recovery period of two hours. The researchers found that growth hormone concentrations were elevated during a marathon run to a greater degree than exercise would elicit alone.
 
Other studies using either resistance trained or physically active individuals showed no increases in plasma growth hormone concentrations following arginine supplementation. When resistance trained males consumed approximately 8 grams of arginine daily for 17 days there was no associated changes in growth hormone concentrations [12]. Similarly, Lambert et al. [13] gave male bodybuilders 1.2 g of arginine and 1.2 g of lysine. This supplementation did not induce a statistically significant increase in serum growth hormone concentrations over a 3 hour period. In a recent review, Chromiak and Antonio [4] highlighted several factors that appear to modify the growth hormone response to amino acid administration. These include training status, age, sex, diet, and time since last meal. Also, the growth hormone response to amino acid ingestion may be reduced in exercise-trained individuals [4]. These authors concluded that the practice of consuming specific amino acids, including arginine, during or after exercise does not appear to be effective [4].

 

Growth hormone, arginine and exercise
Recent studies have shown that resting growth hormone responses increase with oral ingestion of L-arginine and the dose range is 5–9 g of arginine. Within this range there is a dose-dependent increase and higher doses are not well tolerated. Most studies using oral arginine have shown that arginine alone increases the resting growth hormone levels at least 100%, while exercise can increase growth hormone levels by 300–500%. The combination of oral arginine plus exercise attenuates the growth hormone response, however, and only increases growth hormone levels by around 200% compared to resting levels.
Summary: Exercise is a very potent stimulator of growth hormone release and there is considerable research documenting the dramatic growth hormone rise. At rest oral L-arginine ingestion will enhance the growth hormone response and the combination of arginine plus exercise increases growth hormone, but this increase may be less than seen with exercise alone. This diminished response is seen in both in both younger and older individuals.

 
Additionally, although it's been tested in unhealthy people, trials of chronic arginine supplementation in patients with diabetes or various forms of CVD have shown no benefit, and tended to suggest harm (1-5).
 
References
1: Tsai CH, Pan TL, Lee YS, Tai YK, Liu TZ. Evidence that high-dose L-arginine may be inappropriate for use by diabetic patients as a prophylactic blocker of methylglyoxal glycation. J Biomed Sci. 2004 Sep-Oct;11(5):692-6. PubMed PMID: 15316145.

2: Loscalzo J. Homocysteine trials--clear outcomes for complex reasons. N Engl J Med. 2006 Apr 13;354(15):1629-32. Epub 2006 Mar 12. PubMed PMID: 16531615.

3: Jahangir E, Vita JA, Handy D, Holbrook M, Palmisano J, Beal R, Loscalzo J, Eberhardt RT. The effect of L-arginine and creatine on vascular function and homocysteine metabolism. Vasc Med. 2009 Aug;14(3):239-48. PubMed PMID: 19651674; PubMed Central PMCID: PMC2840406.

4: Cosentino F, Hürlimann D, Delli Gatti C, Chenevard R, Blau N, Alp NJ, Channon KM, Eto M, Lerch P, Enseleit F, Ruschitzka F, Volpe M, Lüscher TF, Noll G. Chronic treatment with tetrahydrobiopterin reverses endothelial dysfunction and oxidative stress in hypercholesterolaemia. Heart. 2008 Apr;94(4):487-92. Epub 2007 Oct 4. PubMed PMID: 17916662.
 
5. Andrew M. Wilson, MBBS, PhD; Randall Harada, MD; Nandini Nair, MD, PhD; Naras Balasubramanian, PhD; John P. Cooke, MD, PhD
L-Arginine Supplementation in Peripheral Arterial Disease: No Benefit and Possible Harm


Michael
Aug 23 2017 09:49 PM
Anti-Glycation Synergy

There is no evidence that carnosine inhibits AGE accumulation in vivo.

 

Food phenolics can inhibit the initial stages of glycation in vitro and in food systems, but they don't do so in vivo except maybe, maybe in severe diabetics.


Forever21
Aug 23 2017 06:16 PM
Michael's "Tiered" Supplement

What brand of ubiquinol do you use Michael? No love for Mitoq?


Adaptogen
Aug 23 2017 12:30 AM
Allergies / Allergic Rhinitis Stack

I have some nigella sativa oil that I haven't gotten around to trying yet but it definitely seems promising based on the research. I have used a (counterfeit) bionase and another intranasal LLLt device, which I noticed nothing from. Maybe I didn't use it frequently enough to get results, but having a laser stuck up your nose for 15 minutes a day every day is less fun than it sounds.

I think the ginger and cordyceps are the most effective components of the stack, and the dosage for cordyceps is important IMO, considering the vast majority of clinical studies that achieved significance for respiratory health and exercise capacity were using somewhere in the region of ~3 grams.

I also drink a lot of sencha, I haven't seen much of anything to back it up, but I have a feeling that most types of catechins and egcg (and not just o-methylated catechins in benifuuki tea) have a favorable impact on allergies.


Michael
Aug 22 2017 10:44 PM
Michael's "Tiered" Supplement
(Cnt'd)
Here the intervention group was only a small amount over outright deficiency, and the intervention group was quite high, but there was no effect at all on any cardiovascular outcome; there wasn't even an effect when looking at subjects who started the trial in outright deficiency. They have a point that daily dosing might be better than once-monthly bolus, but that's a pretty slim thread.

These results support prior work by Autier et al (PMID 24622671) showing pretty convincingly that the apparent benefits of high 25(OH)D levels are due to reverse causation: inflammation and a variety of undiagnosed early-stage disease processes lower one's vitamin D levels, so having high vitamin D becomes associated with good health, when it's ill-health driving low D rather than high D driving good health.

At 1000-1200 IU/d, I have consistently had a little over 40 ng/dL serum 25(OH)D3. I've been tapering back for years now to reach the low end of the 30-40 ng/dL range, and at 500 IU/d I am now finally fairly steadily there when measured in what passes for winter in these parts.

AjiPure Taurine: Absent in vegetarian diet; significant, altho' not ideal, data that it reduces the risk of CVD and other mortality.(33) NB that the EPA/DHA and taurine content of fish and seafood are major confounders to drawing inferences about observed benefits of fish consumption in epidemiological studies; while there are controlled trials showing lower risk of a second heart attack or major cardiovascular events with EPA/DHA supplements or extra ALA, there is as yet no real equivalent with taurine. In in Japan, the average intake appears to be 225 mg/d in males and 162 in females, with the highest intakes >1000 mg.(34) Additionally, recent studies have found that some of the endocrinological and "resillience" effects of CR involve the cellular generation of H2S via the transsulfuration pathway;(56-59) and a recent clinical trial(60) not only confirmed a previously-reported hypotensive effect of taurine, but showed that it elevates circulating H2S, and (in rodents) did so by elevating protein expression of the two key enzymes in the transsulfuration pathway. :~ As AjiPure, for reasons discussed under lysine, above.

Rite Aid B-Complex With B12: Rite Aid: who'd'a thunk it?? I've been looking for a supplement like this for years! Provides RDA-ish levels of all B-vitamins, except that it contains no folic acid. I get a ridiculous amount of folate in my diet, I have no MTHFR reductase mutations, and if one does think one needs a supplement (after having first tried just increasing one's intake of green leafy vegetables), one should err on the safe side by avoiding folic acid in favor of L-5-methyltetrahydrofolate. I started taking this in order to more conveniently cover my B12 needs, and in hopes that it plus the small amount of B6 would lower my Hcy. I needed larger-caliber weapons (see above), but continue to take it.

Melatonin: for sleep when stressed, wide awake, or jetlagged. 300 mcg is sufficient to raise levels to normal physiological youthful ones and apparently works as well as higher doses ((22,23), and see (21)) and doesn't produce the 'hangover' sleepiness sometimes seen with the supraphysiological 3 mg (and up) doses that became ubiquitous thanks to the recommendation of the once-notorious Melatonin Miracle.

And with that melatonin discussion, I symbolically put this thing to bed -- for another long sleep!

-Michael

Representative 2-week CRON-O-Meter:


gallery_727_15_193831.jpggallery_727_15_14139.jpg
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57: Nakano S, Ishii I, Shinmura K, Tamaki K, Hishiki T, Akahoshi N, Ida T, Nakanishi T, Kamata S, Kumagai Y, Akaike T, Fukuda K, Sano M, Suematsu M. Hyperhomocysteinemia abrogates fasting-induced cardioprotection against ischemia/reperfusion by limiting bioavailability of hydrogen sulfide anions. J Mol Med (Berl). 2015 Aug;93(8):879-89. doi: 10.1007/s00109-015-1271-5. Epub 2015 Mar 6. PubMed PMID: 25740079.

58: Hine C, Harputlugil E, Zhang Y, Ruckenstuhl C, Lee BC, Brace L, Longchamp A, Treviño-Villarreal JH, Mejia P, Ozaki CK, Wang R, Gladyshev VN, Madeo F, Mair WB, Mitchell JR. Endogenous hydrogen sulfide production is essential for dietary restriction benefits. Cell. 2015 Jan 15;160(1-2):132-44. doi: 10.1016/j.cell.2014.11.048. Epub 2014 Dec 23. PubMed PMID: 25542313; PubMed Central PMCID: PMC4297538.

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pamojja
Aug 22 2017 10:09 AM
Allergies / Allergic Rhinitis Stack

For me black cumin seed oil and guduchi extract brought great improvements with seasonal rhinitis too. Though I take each of the 5 you recommend (not all at that high doses all the times though), they didn't do much in my case. Ascorbic acid in high doses remains the go to remedy against symptoms, when everything else fails.


YOLF
Aug 21 2017 08:49 PM
Allergies / Allergic Rhinitis Stack

I'd add polypodium or it's extract; 20 hydroxyecdysone and black cumin seed oil.  


Adaptogen
Aug 21 2017 12:27 AM
Stength, Endurance, and Vitality: An Exercise-Memetic and Synergism Stack

This is the basic framework (exercise-capacity promoting portion) of a more complete stack that I take on a daily basis.

Additional supplements I take per day are:

  • Japanese Sencha - 10 to 15 grams per day, steeped in kyusu.
  • Spirulina - 3 to 6 grams
  • Vitamin K (menaQ7) - 90 to 180mcg
  • Vitamin D - 1000 to 2000 iu
  • Aged Garlic Extract (Kyolic) - 1800 mg divided into 2 doses
  • Magnesium Glycinate - 400mg before bed
  • Prebiotic formulation (composed of 4 tbsp high-maize resistant starch, 2 tbsp ground flax, bilberry/blueberry extract for gut microbiota modulation).

Lena Mill
Aug 17 2017 06:39 PM
The "I'm Turning 30" Health And Prevention Stack (Suggestions Welcome)

Didn't rate, but you might consider grapeseed extract with the pterostilbene, as alone it can increase LDL cholesterol


ilikenwf
Aug 04 2017 07:29 PM
The "I'm Turning 30" Health And Prevention Stack (Suggestions Welcome)

Nice of you folks to rate this stack and then not give any feedback as to why you're rating it so low.


mitz_petel
Jul 29 2017 04:28 PM
Sleep Stack

Do tryptophan benefits offset its side effects? I read this recently and decided it wasn't worth it: http://www.supplemen...de-effects.html

 

I suggest adding l-theanine instead.


chris85
Jul 25 2017 10:50 AM
Control Rheumatoid Arthritis

If it were me I would take the curcumin, boswellia, and add ashwagandha and ginger to start with.

 

Vitamin D and fish oil yes if you don't spend a lot of time in the sun and eating oily fish.

 

I'd also eat a Paleo style diet without red meat, but plenty of wild seafood. This is important because breads and dairy, possibly nightshades as well could be contributing to the inflammation.


jjnz
Jul 17 2017 08:59 AM
Collagen Hydrolysate Experience

Have used the mentioned product , have tried others too.

I'm currently in the early stages of a multisystemic undiagnosed inflamatory disease, probably RA 

I'm assuming I'm losing collagen as my nails are falling apart, have lines/pits in them and my skin is dry and has lost it's suppleness.

46/m

I haven't noticed any improvement

I also take UC-2 


jjnz
Jul 17 2017 08:45 AM
Control Rheumatoid Arthritis

it's getting away from true anti-inflamatories but I suspect Ive gained an advantage from

UC-2 Undenatured Collagen 1 x at night empty stomach

CMO Cetyl Myristoleate 2x (3x/day) 

Boron 10mg/Day


YOLF
Jun 16 2017 06:51 PM
Collagen Hydrolysate Experience

Mikey, the difference in our age. I'm 35, you're ~64. Collagen supplements are racemic. The "relative age" and health of the animal the gelatin comes from is important, especially as they age faster than we do, The average "relative age" of the animal is likely younger than 64, but may be older than 35. We also never know if the animal it's coming from is healthy or not, or if one bad animal spoiled the collagen supply. More research is necessary and pure specific collagens/elastins should be harvested from gmo bacterial sources and applied according to age and health condition. Otherwise, unless you're old, you're experience with collagen will be inconsistent and you could waste money on kilograms of collagen that is older than the stuff you're making.


pamojja
Jun 11 2017 06:15 PM
PAD and additional Remissions

Some pictures in my dropbox which didn't show in-line.

 

The main stenosis as MRI gif (2009):

https://www.dropbox....orta_1.gif?dl=0

 

Psoriasis (don't click, if you can't see open wounds - 1996):

https://www.dropbox....mshala.jpg?dl=0

 

addendum (3rd July):

.. it was possible:
  • first of all - to reverse a 60% walking disability from PAD
  • ...

Only left to work on are CFS symptoms..

 

Meanwhile could get a 50% disability due to the CFS/ME symptoms again. Helps with yearly tax returns due to high health expenses.

 

For that reevaluation the investigating Neurologist ordered a brain MRI, which found an old stroke in the left cerebellum. Therefore, one more potentially deathly condition not only survived, but not even mentioned its occurrence. ..thought it a miracle to have already outlived the 30% five-year mortality prediction from PAD, but now additional a much worse 50% one-year mortality with stroke!

 

 


  • Chondroitin Sulfate - though not taken consistently as recommended here, after some months on about 5 g/d my intermittent symptoms from PAD completely ceased. And a 60% government-certified walking disability due to that has been revoked since!

 

When further analyzing which intakes have at least 30% increased during the 8 months before this substantial improvement - compared relative to my average intakes during these 9 years (leaving out Ayurvedics, since they all been added later and therefore all higher):

 

126% condroitin sulfate
117% paba
91% inositol
90% glutamine
85% medium chain triglicerides
82% magnesium sulfate
81% menaquinone-7
71% phyloquinone
59% rutin complex
59% kelp
55% cysteine
53% boswellia ext.
49% gingerols
44% tyrosine
44% lycopene
42% grape seed ext.
42% citrulline malate
41% lecithine
39% silica
39% pantothenic acid
39% milk thistle ext.
37% pomegranate ext.
37% methylfolate
36% potassium
36% copper (reduced after, since it caused to high than normal lab values)
35% silymarin
33% manganese
32% beta-carotene
31% punicalagins
30% trimethylglycine
30% ascorbic acid


mikey
Jun 08 2017 05:20 AM
Collagen Hydrolysate Experience

I take 2+ (24+ grams) tablespoons of the Great Lakes hydrolyzed gelatin a day and yes, I have noticed a difference in my skin texture as well as my apparent ability to recover and the health of my connective tissues. These are subjective considerations, though. Just my thoughts. 

 

With all due respect, I have a different opinion, Yolf.

 

Great Lakes appears to be transparent about the quality of their collagen, which is from grass-fed beef, which means that Great Lakes is aware of the inferiority of grain-fed beef products, in general. 

 

Also, marbled steak is grain-fed, which means that it is inferior for purposes of longevity, as consumption of grain-fed beef is associated with an increased risk of cancer, cardiovascular disease and an increased risk of a shorter lifespan, as per a large Harvard study.
http://www.michaelmo...Meat_Kills.html
 

My current interest in hydrolyzed collagen comes because of a couple of years of highly "painful" parasthesia in my left hand caused by spinal stenosis and degenerated discs.

I had one of UCLA's best neurosurgeons recommend that I have a triple fusion in C-5-6+7.

 

I will not have a fusion.

 

I am attempting to do the 15th "medically impossible" thing that I have documented in re-aligning the misaligned vertebrae and regenerating the discs.

 

A 77-year old friend that has three degenerated lumbar discs reported that his "alternative" chiropractor recommended that he take the same Great Lakes Grass-Fed hydrolyzed collagen that you are asking about (two+ tablespoons a day), take 50 mg of manganese a day and use a Saunders traction device to pull the vertebrae/discs apart.

 

Within a year he reported that a new scan showed an approximate 80% improvement in disc height/volume.

 

I've been doing the same, except that I am seeing a doctor that has a traction unit that goes up to 35 pounds.

 

I report that the parasthesia in my left hand is about 10-20% as "painful" as it was about three years ago, so I am making progress.

 

I should note that back in the '90's Knox (gelatin) paid me a consulting fee in which I advised them to make the first hydrolyzed collagen product that eventually turned into the best-selling Knox NutraJoint.

 

Before that old-timers will remember that one had to dissolve gelatin in hot water to solubilize it. Hydrolyzing it breaks into tiny particles that dissolve in cold water, too. So, I have a history of studying this, although it was a long time ago and much research has taken place since then.

 

Published data show that hydrolyzed collage (gelatin) appears to preferentially go to collagenous tissues. This has been shown using 14C-labeled gelatin hydrolysate. https://www.ncbi.nlm...pubmed/11071580

 

One could hypothesize that humans are genetically adapted to ingest collagen via consumption of gelatin when eating animal tissues, and that a lack of regular ingestion of this raw material building block over a long period of time results in the loss or degradation of such tissues, in bones, connective tissue and skin (wrinkling). This notion is almost like thinking that collagen is a bit like an essential nutrient. If we don't get enough of it there is unnecessary, accelerated or premature aging caused by a deficiency.

 

Data show improvements in function for athletes - "Collagen hydrolysate is a nutritional supplement that has been shown to exert an

anabolic effect on cartilage tissue. Its administration appears beneficial in patients with osteoarthritis." 
https://www.ncbi.nlm...in skin.</span>

https://www.ncbi.nlm...ubmed/23949208/

https://www.ncbi.nlm...ubmed/21480801/

 

As to type l, ll and lll, I believe that there is merit in consuming sources of all three.

 

Also worth noting is that vitamin C is required for collagen formation, and a lifelong deficiency of vitamin C appears to predict more wrinkling of skin and loss of bone density. Most Americans only get about 300 mg of vitamin C a day.

 

One study looked at what we would get from a potential hunter-gatherer diet and found that such a diet would provide something around 2,300 mg of vitamin C a day. Is this more representative of what we are genetically-programmed to consume?

https://www.ncbi.nlm...cles/PMC283405/

 

If that is true, it could be one explanation for why the typical American is wrinkled and experiences a significant loss bone density as healthy bone is about 30% collagen and it is mostly collagen that gives bone its "flexibility," so that it absorbs impact without fracturing.
https://www.ncbi.nlm...pubmed/11149477

 

Best wishes!


YOLF
May 21 2017 01:47 PM
Collagen Hydrolysate Experience

I've seen better results with other stuff. The trick with collagen is the source. Beef Collagen is usually type I and III and can be sourced from aged cows who might be in worse shape than you as marbled steak is preferred and comes from older cows. It also contains alot of lysine which can harm your kidney's in the long term. There are definitely better options that will prove to be more consistent.


McSchwangstasis
May 20 2017 03:56 PM
My Stack (good for vegetarians/OCD personalities)

Okay 05/20/2017 edit, removed dutasteride due to negative effects on alloprogenalone.


Long John Silver
Apr 24 2017 06:21 PM
First - light - stack without any -racetam

Thank you Adam, your advice is really welcome !

I've heard contrasting opinions on both bacopa and rhodiola. I thought that alpha gpc + 1 ingredient (like uridine, as you said) would be sufficient for my purpose.

Any opinion about dosage ?

Thanks again!


Adam Karlovsky
Apr 24 2017 09:47 AM
First - light - stack without any -racetam

I am wary of huperzine, I think it would lead to downregulation of the cholinergic system, unless there is evidence to say otherwise. Galantamine would be a better option, but is often only available via prescription, and you'd only want to be taking a tiny amount if you lack relevant disease states.

I recommend checking out bacopa and rhodiola for a natural, mild cognitive boost.

Coffee would also be preferred over caffeine, as coffee contains beneficial phytonutrients in it that make it a health-promoting form of caffeine.
Seafood (even canned) would be preferred over omega 3s, as they contain health-promoting dipeptides and are more suredly health-promoting than fish oil.

Alpha GPC is a good choice, you might like to add Uridine as they are a good combo. Theanine is always good and cheap too.


Adam Karlovsky
Apr 16 2017 12:55 AM
Longevity & Mood Stack (Comprehensive)

Why would I want to use insulin spray in the morning? I imagine that just give me low blood sugar (perhaps deepen ketosis) and little to no other benefits.

Phenibut has been a life-changer for me - increasing sleep quality at night is much more important than making up for sleep-deficit related mood problems during the day. Sleep is fundamental, if you get it right, then you'll have phenibut-like effects throughout the day just naturally. I think many people with depression and anxiety have sleep issues, and fixing sleep can help reduce depression and anxiety. Have you tried taking phenibut for sleep? Most people haven't, in fact most people in the west don't even use it therapeutically, they'll tend to use it recreationally, which I think is really, really dumb (unsafe).

As of the date of this post, I have done many bouts of ketosis and fasting over the years, but I haven't done rapamycin yet. The logic behind adding rapamycin adjunct to the fast is to drastically increase autophagy in a small period of time. It's about time-efficiency, fasting and rapamycin each have side effects, and I'd rather get the side effects over and done with in a week rather than draw it out over the year with chronic rapamycin intake and regular bouts of fasting. There is also evidence that fasting really only effects autophagy effectively when sustained for many days in a row, as such, I assume regular, short fasts is not very useful for longevity, and the reviews on human fasting seem to agree.


Maxpower
Apr 15 2017 11:01 AM
Long term mental maintenance stack

There seems to be a fair bit of ANECDOTAL evidence that Lions Mane provides benefits with long term usage, though of course, some people dont seem to get any effects from it. I intend to take it for the next few months, thinking that it cant hurt, even if it does not do much for me.

As for the Noopept, up until recently I had been drinking too much for too long, though I have cut back significantly now. From what I have read, Noopept is good for repairing damage done by previous excessive alcohol consumption. From what I have read, both Noopept and Lions Mane both provide neurogenesis and other similar benefits, though I am not sure if there is any point in taking both, or if they both work on the same areas??? Any ideas?

   I would love to eat more fish, but fish oil tablets are soo convenient. Not sure exactly what they do though.


Adam Karlovsky
Apr 13 2017 06:32 AM
Long term mental maintenance stack

Not sure how Lions Mane got in there, there isn't much evidence for how it works or what effects it has in humans.

 

I'm not a big fan of fish oil, doesn't seem to do much of anything, better to just eat more seafood.

 

I prefer piracetam over noopept, for everyday use. Noopept might be more appropriate in cases of brain trauma, but piracetam has a more thorough safety profile otherwise.

 

When I posted this comment, you hadn't filled out any dosages, so I can't comment on that.


Zed
Apr 09 2017 11:41 AM
Longevity & Mood Stack (Comprehensive)

Interesting. How about an an intranasal insulin spray in the morning? - along with eliminating the Phenibut at night - I think its a waste of its effects of enhancing sociability to use it at night. Much rather micro dose it during the day or cycle on and off. 

 

>Each winter I plan to do a month of ketosis and a long (5 day+) fast with rapamycin adjunct

Have you actually done this? and whats the deal with rapamycin adjunct?

 

Cheers


Topaloff
Apr 03 2017 07:50 PM
Pre/Post-Workout Stack

i found out that anything lower that 30g of whey protein post-workout will give me a darned muscle soreness that keeps going for days.

Also, BCAAs help me a lot and i can definitely see an improvement.

I lift moderate weights but my training is very intense.

what about yours?


Adam Karlovsky
Mar 07 2017 07:11 AM
Immunity and anti-cancer stack. Please review!

Also, it is important to know whether the type of cancer or infection is helped or hindered by antioxidant supplementation. Many cancers are made worse by antioxidant supplementation, so if the supplement doesn't have in vivo evidence for hindering the particular cancer then you should, conservatively, probably not take it.


Adam Karlovsky
Mar 07 2017 07:04 AM
Immunity and anti-cancer stack. Please review!

I don't know how much evidence there is for these, but based on my priors about their magnitude of effect, I'd personally start with reishi, monolaurin and cat's claw. 

You're already using reishi, one thing to think about is quality, there are lots of low quality reishi products, I get mine from nootropicsdepot. 

 

Maybe do some more research on the other two and get back to us with a opinion/review?


Cobaltus
Jan 30 2017 09:16 AM
Cobaltus Stack

Note #1: Yesterday evening i noticed nose bleeding: blood was pretty liquid and kept flowing for a while before clotting properly. I am reducing the gingko biloba intake from 120mg/day to 60 mg/day. Luckily enough I already posted the right dosage yesterday but... how will I change the stack ingredients next time?