33 replies to this topic

[neogenic]

What are each of the mechanisms of aging and what supplements/drugs best address each directly?
Like (and I may be wrong, if so please enlighten)
Advanced Glycation Endproducts (AGEs) - pyridoxamine, r-ALA, berberine, metformin
Methylation Dysfucntion - SAMe, Creatine, Betaine, 5-MTHF, Methylcobalamin, P5P, etc.
Oxidation - Spin Traps, Antioxidants, etc.
Mitochondrial Dysfunction - CoQ10, PQQ, etc.

[Guardian4981]

I like Country Lifes B complex which helps with all areas you list.

[Kevnzworld]

I would add up regulating NAD/Sirt1 with a form of niacin, like nicotinamide riboside and resveratrol.
to the antiglycation regimen : Carnosine and lower dose benfotiamine.
Mitochondrial dysfunction : C 60oo, possibly MitoQ

Edited by Kevnzworld, 27 March 2014 - 04:29 PM.

[albedo]

Next to methylation disfunction, oxidation and glycation I feel often the (cronic) inflammation is forgotten while it is linked to a multitude of diseases. I personally take care to check my CRP and fibrinogen (next to the more usual cholesterol, homocysteine and other markers). I also had a prostate condition which makes me even more committed to fight inflammation increasing vegetables and fatty fishes consumption, exercise and supplementing with curcumin, zyflamend, ginger and others.

[niner]

Methylation dysfunction? That doesn't usually show up on lists of causes of aging. I suspect that's because it isn't universal. If you have a severe methylation problem (either hyper or hypo) then yeah, it would probably shorten your life, but how many people are that far off of normal? I might be wrong, but I have a feeling that the internet grossly overestimates the number of people for whom methylation is a serious problem.

[gt35r]

Methylation dysfunction? That doesn't usually show up on lists of causes of aging. I suspect that's because it isn't universal. If you have a severe methylation problem (either hyper or hypo) then yeah, it would probably shorten your life, but how many people are that far off of normal? I might be wrong, but I have a feeling that the internet grossly overestimates the number of people for whom methylation is a serious problem.

I think he means gene expression changes. As we age certain genes get expressed to frequently and others too little. I believe the SIRT family largely makes sure over acetylation does not occur.

The being said, I do not know if any of the supplements listed on his post have an known efficacy for this mechanism of aging.

[nowayout]

Creatine appears to reduce lipofuscin accumulation in rodents. So does ALCAR.

MK-7 may reduce or even reverse vascular calcification.

Edited by nowayout, 27 March 2014 - 10:45 PM.

[Dorian Grey]

IP6 (Inositol Hexaphosphate)?

You might be interested in Bill Sardi's: "A Unifying Theory of Aging"
http://www.longevine...of-aging-part1/

Be sure to click ahead to pages 2, 3 & 4.

[Kevnzworld]

Methylation dysfunction? That doesn't usually show up on lists of causes of aging. I suspect that's because it isn't universal. If you have a severe methylation problem (either hyper or hypo) then yeah, it would probably shorten your life, but how many people are that far off of normal? I might be wrong, but I have a feeling that the internet grossly overestimates the number of people for whom methylation is a serious problem.

Most people that I talk to that get their homocysteine checked find that it's 10+. Mine was 12 , and I was taking folic acid back then. It's now 7.
I think that chronic elevated homocysteine levels contribute to many degenerative diseases including Alzheimer's and CVD.

Edited by Kevnzworld, 28 March 2014 - 01:34 AM.

[ta5]

The OP may be interested in the thread:
Supplementation Choices Based on the 7 SENS Research Foundation Targets

Most people that I talk to that get their homocysteine checked find that it's 10+. Mine was 12 , and I was taking folic acid back then. It's now 7.

How did you get it down to 7?

IP6 (Inositol Hexaphosphate)?

You might be interested in Bill Sardi's: "A Unifying Theory of Aging"
http://www.longevine...of-aging-part1/

Be sure to click ahead to pages 2, 3 & 4.

I've been looking at IP6. I bought some a year ago. Since it inhibits absorption of several minerals, I can't figure out if it's safe or not, how to take it, or how much to take.

[Dorian Grey]

IP6 is considered an "anti-nutrient" as it strongly binds to dietary minerals when phytic acid is present in food or IP6 is taken with food/meals.

If taken with meals, IP6 will get too loaded up with dietary minerals to have much therapeutic effect, but when IP6 is taken on an empty stomach with a full glass of water, IP6 will enter the blood intact, where it will bind free iron (the most dangerous kind, responsible for Hydroxyl Radicals). The uptake is very rapid and IP6 will not affect mineral absorption from meals as long as you take it 30-60 minutes before eating.

IP6 can also bind some good minerals in blood/body tissues like zinc, so it's best not to overdo use of IP6. I take 500mg about 3 days a week on an empty stomach. If you're supplementing any zinc at all (taken well apart from IP6), this should prevent any deficiency.

The other minerals IP6 is known to affect, like calcium & magnesium are "macro-minerals" abundantly present in the diet and are rapidly replaced from dietary sources provided you don't take IP6 with meals, or consume large amounts of foods high in phytic acid with most meals.

As with most supplements... Megadosing is unwise. More is not better; but a little IP6, taken properly will greatly reduce hydroxyl oxidative stress from free iron. I actually "feel different" on days I take IP6. Sleep like a baby when I take it before bed, but you should have about 4 hours after dinner before dosing with IP6.

Edited by synesthesia, 28 March 2014 - 02:23 AM.

[albedo]

Synesthesia, I think I had a good success with IP6 (yes, taken on empty stomach and in the morning and only 1/2 of the recommended dose only (*), i.e. 400 mcg!) and for ferritin went from an average of 262 ng/mL(ref. 22-275) over 10 years to 98. (*) I know this is rather art than science but I am very (too?) cautious and tend rather to look at long term than immediate effects.

[Jackemeyer]

What are each of the mechanisms of aging and what supplements/drugs best address each directly?
Like (and I may be wrong, if so please enlighten)
Advanced Glycation Endproducts (AGEs) - pyridoxamine, r-ALA, berberine, metformin
Methylation Dysfucntion - SAMe, Creatine, Betaine, 5-MTHF, Methylcobalamin, P5P, etc.
Oxidation - Spin Traps, Antioxidants, etc.
Mitochondrial Dysfunction - CoQ10, PQQ, etc.

Though Aubrey has refused to advocate preventative measures in the shared quest of making negligible the mechanisms-of-aging-as-we-know-it, his brilliant engineering project nevertheless aids the prevention-minded. Your questions and many on this forum regarding regimens are important in our minds too, as we appreciate and follow a similar approach at Live120Plus.

Our project (approaching 2 years of funded progress) is based on the premise that if you embrace and practice every one of the hundreds of activities in every area of human health and longevity science, which research has shown in a mammalian or human study to reduce the risk of or to ameliorate one or more human diseases, disorders or dysfunctions or to actually increase healthful longevity, then you may well be able to remain in good function until 120 years of age (given that you are not already dysfunctional or diseased when you begin and that you carefully avoid unnecessary overt risks to your person and your health).

At this time we are in greatest need of:
1) several more health/longevity scientific literature researchers/writers and
2) a website developer.

However, such people must also be longevists practicing one or more currently proposed health/longevity methods and fully willing to make all their practices and health test parameters open to subscribing clients of Live120Plus, as is the case for all current team members. If you can help us to find such people, that would greatly accelerate our progress. We function as a team (partners and associates) with input from everyone and pay a combination of salary plus investment in the project.
Thanks in advance for reviewing our site (in progress).
Jack

-------More intro detail, below-------
Our premise is based on the simple logic that if you constantly work to increase the age of onset of each and every disease, disorder and dysfunction that might become the effective cause of your death, then it is not clear that and how you will ever die (although clearly the accumulation of cellular damage is such that with currently available approaches, not all such mortalities can be indefinitely delayed).

I invite you to have a look at the summary descriptions of our approach on the website http://Live120Plus.com which will eventually hold all the regimens of recommendations, reasoning behind our recommendations, journal references for all recommendations, and client individualized regimen data, test results, etc. Note that "registration" is not yet implemented, but that all top left menu pages are publicly accessible. The details of these summary regimen descriptions are being researched, organized and written on a development private wiki (LERDIT.org) and will be transferred to Live120Plus when sufficiently complete to attract and benefit subscription clients.

[albedo]

What are each of the mechanisms of aging and what supplements/drugs best address each directly?
Like (and I may be wrong, if so please enlighten)
Advanced Glycation Endproducts (AGEs) - pyridoxamine, r-ALA, berberine, metformin
Methylation Dysfucntion - SAMe, Creatine, Betaine, 5-MTHF, Methylcobalamin, P5P, etc.
Oxidation - Spin Traps, Antioxidants, etc.
Mitochondrial Dysfunction - CoQ10, PQQ, etc.

Though Aubrey has refused to advocate preventative measures in the shared quest of making negligible the mechanisms-of-aging-as-we-know-it, his brilliant engineering project nevertheless aids the prevention-minded.........

Thank you Jackemeier. I bookmarked your site, interesting. However, I am curious to know what makes you saying Aubrey is not advocating preventative measures. At least as far as health span is concerned (vs life span and max longevity). It is just a question if you dare to point to where Aubrey tell us that. I do not think he can claim against good nutrition, exercise etc .. I understand the point Michael Rae makes on lack of support for almost all supplementation we look at tough while scientific support is important on CR etc... Can you be more precise?

[maximum411]

I would focus mainly on compounds that reduce DNA damage, as a number of plant polyphenols have been shown to do, as well as compounds that reduce the buildup of harmful protein and lipid aggregates (as centrophenoxine has for lipofuscin). Honestly, though, I think a results-based approach is better than a mechanism-based approach, as any proposed mechanism for aging is pretty much theoretical. Which substances have actually extended lifespan in mammalian model organisms? Off the top of my head, I can think of deprenyl, melatonin, and metformin, and I am sure there are many more. The reason I think DNA damage and mutation are important no matter what is that cancer is a part of the aging process, and we clearly know cancer to be caused by genomic damage. If you want to live long, you will need to keep your DNA from accumulating mutations and lesions, because if you have enough mutations you will inevitably get cancer.


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[Dorian Grey]

DNA protection/repair? IP6 to the rescue again!
http://www.ncbi.nlm....pubmed/11030616

Binding of inositol phosphate to DNA-PK and stimulation of double-strand break repair

"In mammalian cells, double-strand breaks in DNA can be repaired by nonhomologous end-joining (NHEJ), a process dependent upon Ku70/80"

"we identify this factor as inositol hexakisphosphate (IP6). Purified IP6 is bound by DNA-PK and specifically stimulates DNA-PK-dependent end-joining in vitro"

Edited by synesthesia, 29 March 2014 - 04:34 PM.

[Kevnzworld]

DNA protection/repair? IP6 to the rescue again!
http://www.ncbi.nlm....pubmed/11030616

Binding of inositol phosphate to DNA-PK and stimulation of double-strand break repair

"In mammalian cells, double-strand breaks in DNA can be repaired by nonhomologous end-joining (NHEJ), a process dependent upon Ku70/80"

"we identify this factor as inositol hexakisphosphate (IP6). Purified IP6 is bound by DNA-PK and specifically stimulates DNA-PK-dependent end-joining in vitro"

Ok, you've convinced me, I'm especially interested in IP6 as a method to remove excess iron to reduce lipofuscin.

[Dorian Grey]

The relatively minor risk of transient micro-mineral depletion compared to the potential rewards of controlling age related over-mineralization are compelling to me also... Effective DNA maintenance is the icing on the cake.

The more I read about the role of iron (and copper) in age related disease, the more convinced I become controlling accumulations of these metals may be a major player in longevity. The fact that there really is no known benefit to carrying around excesses of these metals makes the rationale for keeping them low even more logical.

The ocean of evidence compiled by HEALTHeIRON http://www.healtheir...science-library is absolutely astounding. Spend a couple of hours surfing this site when you can.

Edited by synesthesia, 29 March 2014 - 05:55 PM.

[Ehvam]

Wow, this thread has lead to so much information and learning for me as far as longevity is concerned! I've never given longevity much thought since I come from a family that regularly lives well into the 90s-100s and remains active throughout. I always assumed it was simple genetics. But the family that migrated to the USA has not as much luck.

I've supplemented as a way to maintain health- quality fo life is so much more important to me than length.. yet the two are related so I've been thinking about it and deicded to look into improving my odds, so to speak.

This thread has lead to alot of information and I am convinced, I started IP6 this morning to remove iron stores i have always had exceedingly high iron and hematocrit levels, almost to the point of concern for doctors and have added PQQ as well as carnosine to my regimen.
As I learn more I may add to the list... epithalon looks really interesting,as well as astralugus...


I just really wanted to thank all of you for sharing your knowledge.

[Dorian Grey]

Thanks for the feedback Ehvam. I'm interested in hearing what you think of IP6 once you've tried it.

IP6 only chelates serum iron, which is the most dangerous kind due to its highly reactive nature. When serum iron is low, the body responds by breaking down ferritin (stored iron) to maintain red blood cell formation. Thus, IP6 "cures" elevated serum iron almost instantly, while ferritin will fall much more slowly.

A sharp drop in serum iron (when it is elevated) should produce dramatic and swift results if you are experiencing any symptoms of oxidative stress. Remember to take IP6 on a very empty stomach with at least 6 oz of plain water; and as always... Moderation in all things (including IP6)!

Let us know how things go for you with this new supp.

[nowayout]

Exercise outperforms pretty much any known supplements and drugs by orders of magnitude as far as healthy biomarkers are concerned, so it should be at the top of the list before any supplements are even considered. Exercise should include weight training and some form of cardiovascular exercise (though perhaps not steady-state cardio).

[Kevnzworld]

Exercise outperforms pretty much any known supplements and drugs by orders of magnitude as far as healthy biomarkers are concerned, so it should be at the top of the list before any supplements are even considered. Exercise should include weight training and some form of cardiovascular exercise (though perhaps not steady-state cardio).

I agree that exercise ( and a healthy diet ) are important aspects of any anti aging regimen.
It won't however necessarily effect many of the " biomarkers " that plague an aging body in a significant way.
It may support better hormone levels, but won't raise age related declining ones significantly ( DHEA, testosterone, melatonin etc )
It won't lower inflammation ( CRP, sedimentation rate ) age related or otherwise.
It won't improve methylation ( homocysteine )
It will support lower fasting blood glucose levels, but not inhibit glycation ( HbA1C )
It will support better lipid patterns, but not significantly adjust higher LDL 's in a person of normal weight.
It won't lower levels of oxidation, in fact it is pro oxidant.
It won't improve mineral/ nutrient status and make up for dietary deficiencies.
It supports a heathy lifespan, but won't potentiate a longer lifespan in a significant way as substances discussed like C60oo, MitoQ, nicotinamide riboside + resveratrol , PQQ, and others may...

That being said, I will reiterate that resistance / weight training and CV exercise, 45 minutes 4-5 days a week are a critical part of an overall longevity program.
An intelligent, targeted supplement ( drug ) regimen is complementary to an exercise and diet program, not a replacement for one.

[nowayout]

It won't lower inflammation ( CRP, sedimentation rate ) age related or otherwise.
It won't lower levels of oxidation, in fact it is pro oxidant.

I think these two statements are incorrect. It has been discussed in these forums before, and at the moment I don't have the time to cite sources, but exercise certainly lowers chronic inflammation, and while briefly pro-oxidant, exercise hormetically upregulates antioxidant mechanisms greatly so that the net baseline effect is significantly antioxidant (except maybe steady-state cardio, which I avoid).

Edited by nowayout, 30 March 2014 - 12:56 AM.

[albedo]

.....
The more I read about the role of iron (and copper) in age related disease, the more convinced I become controlling accumulations of these metals may be a major player in longevity....

Yes and this is a recent study on the role of copper which looks reinforcing the growth of tumors (bold is mine)

"...This paper describes the mechanism by which copper mediates the interplay between the two energy-producing pathways, respiration and glycolysis. Many tumors produce increased levels of lactate, even when oxygen abounds, reflecting aerobic glycolysis (“Warburg effect”), whereas most normal tissues solely use respiration. We demonstrate that reducing systemic copper with a chelating drug impaired mitochondrial energy metabolism and decreased ATP levels despite induction of glycolysis. We propose that the metabolic phenotype of tumors is modulated in part by variable levels of copper in tumor microenvironment. Our work identifies copper as a tumor promoter by demonstrating that chronic exposure to elevated levels of copper in drinking water—to the maximum allowed in public water supplies—accelerates tumor growth in mice. ..."

http://www.pnas.org/...431110.abstract

Thank you for the pointer to HealteIron. Massive information!

Edited by albedo, 30 March 2014 - 10:59 AM.

[niner]

.....
The more I read about the role of iron (and copper) in age related disease, the more convinced I become controlling accumulations of these metals may be a major player in longevity....

Yes and this is a recent study on the role of copper which looks reinforcing the growth of tumors (bold is mine)

"...This paper describes the mechanism by which copper mediates the interplay between the two energy-producing pathways, respiration and glycolysis. Many tumors produce increased levels of lactate, even when oxygen abounds, reflecting aerobic glycolysis (“Warburg effect”), whereas most normal tissues solely use respiration. We demonstrate that reducing systemic copper with a chelating drug impaired mitochondrial energy metabolism and decreased ATP levels despite induction of glycolysis. We propose that the metabolic phenotype of tumors is modulated in part by variable levels of copper in tumor microenvironment. Our work identifies copper as a tumor promoter by demonstrating that chronic exposure to elevated levels of copper in drinking water—to the maximum allowed in public water supplies—accelerates tumor growth in mice. ..."

Copper is absolutely on my 'toxic crap to be avoided' list. Liver and mollusks have massive quantities, but it's also in soy products, sesame seeds, cocoa/chocolate, and various nuts and beans in non-trivial amounts. It is very common to find copper plumbing in American homes, institutions and businesses, and yes, it leaches into the water. Unless your dietary and living situations are pretty unusual, I think supplementing copper is a distinctly bad idea. Even if you take zinc, unless you're going nuts with it.

[mikey]

Creatine appears to reduce lipofuscin accumulation in rodents. So does ALCAR.

MK-7 may reduce or even reverse vascular calcification.

Reducing, yes. Reversing ?

MK-4 reversed arterial plaque in rats 37% in six weeks, but I don't know of any publication that confirms that MK-7 also reverses it.

I take both, because they may have beneficial effects that are unique and not shared.

Does anyone know of publication confirming that MK7 reverses plaque?

[mikey]

.....
The more I read about the role of iron (and copper) in age related disease, the more convinced I become controlling accumulations of these metals may be a major player in longevity....

Yes and this is a recent study on the role of copper which looks reinforcing the growth of tumors (bold is mine)

"...This paper describes the mechanism by which copper mediates the interplay between the two energy-producing pathways, respiration and glycolysis. Many tumors produce increased levels of lactate, even when oxygen abounds, reflecting aerobic glycolysis (“Warburg effect”), whereas most normal tissues solely use respiration. We demonstrate that reducing systemic copper with a chelating drug impaired mitochondrial energy metabolism and decreased ATP levels despite induction of glycolysis. We propose that the metabolic phenotype of tumors is modulated in part by variable levels of copper in tumor microenvironment. Our work identifies copper as a tumor promoter by demonstrating that chronic exposure to elevated levels of copper in drinking water—to the maximum allowed in public water supplies—accelerates tumor growth in mice. ..."

Copper is absolutely on my 'toxic crap to be avoided' list. Liver and mollusks have massive quantities, but it's also in soy products, sesame seeds, cocoa/chocolate, and various nuts and beans in non-trivial amounts. It is very common to find copper plumbing in American homes, institutions and businesses, and yes, it leaches into the water. Unless your dietary and living situations are pretty unusual, I think supplementing copper is a distinctly bad idea. Even if you take zinc, unless you're going nuts with it.

Odd. The vilification of an essential mineral. "Essential" meaning that we must have some intake of it or we will die.

Copper, like iron has a narrow safety range. There is an intake range where it provides important health-supporting effects, such as its role in copper-zinc super-oxide dismutase and a range where there is too little - deficiency - and a range where there is too much, resulting in toxicity.

Rather than say that nutrients that have narrow safety ranges, such as copper, iron and vitamin A are toxic or to be completely avoided, isn't it more accurate to identify copper's safety range?

Certainly, if one is deficient in copper, one is more likely to lose hair, or experience premature graying of hair, suffer immune dysfunction, skin problems, arryhthmia and a host of other health problems.

[nowayout]

Does anyone know of publication confirming that MK7 reverses plaque?

It is not yet definite, but a talk on unpublished data discussed at this link suggests that it may.

http://www.knowguff....elasticity.html

In the study, 244 healthy postmenopausal women received 180 µg of MK-7 daily, or placebo, for 3 years. The clinical endpoints included bone mineral density, bone strength, and vascular characteristics measured by ultrasound and pulse-wave velocity (PWV, which evaluates age-related stiffening of blood vessels).

...

With respect to the cardiovascular benefits, the study showed substantial benefits in preventing age-related stiffening of arteries in the MK-7 group, while the placebo group saw an increase in the PWV.

However, the most amazing finding was that "nutritional doses" of MK-7 not only prevented stiffening, it also resulted in an unprecedented statistically significant improvement of blood vessel elasticity both measured with ultrasound and PWV. Of course, based on the mechanism of vitamin K's activity, this implies that pre-existing calcification in the arteries was reversed (although it would have been icing on the cake, if the study actually measured the calcium content in the blood vessels).

...

Previously, the benefits of vitamin K on bone and vascular health had been demonstrated with "pharmacological doses" of synthetic forms of vitamin K (as MK-4) of up to 45 mg daily (note 1 mg = 1000 µg). Remarkably, the effects of MK-7 at 180 µg/day were even more pronounced than those in trials using a high dose of one of the synthetic forms of vitamin K.

Edited by nowayout, 31 March 2014 - 12:26 AM.

[Dorian Grey]

The friendly folks at acu-cell (hair mineral analysis) have a page on the likelihood of copper deficiency that has stuck in my mind...
http://www.acu-cell.com/crcu.html
"Chromium (Cr) and Copper (Cu) are associated trace elements, and considered essential to human health.
Next to calcium and magnesium, chromium and copper are important nutrients for their anti-inflammatory
properties. While neither one - with few exceptions - is generally found to be very deficient level-wise,
chromium is on average always lower than copper, with virtually no exceptions. Copper on the other hand is
elevated in the majority of patients, which creates a chronic copper / chromium conflict ratio-wise in these
individuals.
Of thousands of patients tested since the mid 1970s from different
continents around the world, nearly 90% exhibited a chemical profile
that in addition to their own unique chemistry, contained an under-
lying pattern that reflected the impact of elevated copper levels"

Edited by synesthesia, 31 March 2014 - 12:38 AM.

[mikey]

Does anyone know of publication confirming that MK7 reverses plaque?

It is not yet definite, but a talk on unpublished data discussed at this link suggests that it may.

http://www.knowguff....elasticity.html

In the study, 244 healthy postmenopausal women received 180 µg of MK-7 daily, or placebo, for 3 years. The clinical endpoints included bone mineral density, bone strength, and vascular characteristics measured by ultrasound and pulse-wave velocity (PWV, which evaluates age-related stiffening of blood vessels).

...

With respect to the cardiovascular benefits, the study showed substantial benefits in preventing age-related stiffening of arteries in the MK-7 group, while the placebo group saw an increase in the PWV.

However, the most amazing finding was that "nutritional doses" of MK-7 not only prevented stiffening, it also resulted in an unprecedented statistically significant improvement of blood vessel elasticity both measured with ultrasound and PWV. Of course, based on the mechanism of vitamin K's activity, this implies that pre-existing calcification in the arteries was reversed (although it would have been icing on the cake, if the study actually measured the calcium content in the blood vessels).

...

Previously, the benefits of vitamin K on bone and vascular health had been demonstrated with "pharmacological doses" of synthetic forms of vitamin K (as MK-4) of up to 45 mg daily (note 1 mg = 1000 µg). Remarkably, the effects of MK-7 at 180 µg/day were even more pronounced than those in trials using a high dose of one of the synthetic forms of vitamin K.

Thank you. Great data. Studying the effect MK-7 has in activating matrix-GLA protein one would think that it could reverse arterial calcification, which is the main reason I take it. It also lasts about 3 days in the body, so it's "easier" to work with than MK4, which has a 1-2 hour half life and so requires dosing three times a day.

I had a coronary scan that surprised me by showing plaque, when I would assume, based on a scan 14 years ago and my careful diet and supplementation, that I would have none. Researching how to reverse plaque I saw the MK4 study so I started taking 15 mg of MK4 t.i.d. and 300 mcg of MK7 daily - about three months ago.

My blood pressure had also been rising - very scary, which predicts eventual stroke or heart attack. But it indicates arterial wall stiffening.

Today my blood pressure measured 118/76. It has dropped considerably. I am also having acupuncture that has noticeably reduced my blood pressure, so I can't say the MK4 and 7 have done this wonder alone, but the combination of all that I am doing have reversed what was looking like I was moving towards an early death and that is NOT the goal.

.