75 replies to this topic

[nowayout]

Here is my current regimen. It is very minimal compared to that of some others here. My philosophy on this is explained below.

These are all daily doses:

• AOR multi basics 3: 1/3 dose
• Vitamin D3 400 IU (for a total of 733 IU with the AOR above)
• Exercise (as the best antioxidant there is)
• Omega 3 (fish oil) 1g
• ALCAR 250 mg
• Glucosamine sulfate 500mg + Chondroitin sulfate 300mg + MSM 75 mg
• 20 g Vegan protein supplement daily (bean/hemp-based)
• 2 ml Minoxidil topical
• 1/60 mg Finasteride topical (maximum topical dosage that does not affect systemic DHT)
• Tretinoin 0.05% topical on face/neck nightly
• Amitriptylene 10mg

Notes:

• My diet is already sufficient or even excessive in most vitamins and minerals, except for maybe one or two depending on the day, according to the Cron-ometer (I do not practice CR, though). I therefore only take 1/3 dose of the multi as an insurance strategy.
• I do not take megadoses of antioxidants due to their potential blocking effect on the hormetic adaptations induced by exercise. Exercise seems by far the best antioxidant there is and I don't want to interfere with it.
• The Amitriptylene is by prescription for long-term chronic rhomboid spasm and is a short-term addition (six months at most, I hope).
• I am using the ALCAR for anti-aging purposes, but I titrated the dosage according to the effect I feel on the chronic rhomboid injury, given its usefulness for neuropathic pain. I find that 250mg makes it feel much better, while 500mg makes it feel worse.
• I am taking the Vegan protein supplement because my digestive system cannot handle whey products for some reason.

I train with weights most days and do cardio every second day.

I eat a varied diet but most days with no refined sugar or refined carbs, my main carb intake being via oatmeal and some fruit. I eat lots of vegetables and two servings of meat (mostly pork, chicken, or fish) daily, along with nuts, berries and plain organic probiotic yoghurt and kefir. I use olive oil and like avocados. I like having a glass of red wine most days and a little dark chocolate. I like espresso coffee and rooibos tea.

I would like to gain some muscle mass but have always had a difficult time keeping any additional weight on any diet. My body seems to have a set point and any temporary increase in mass causes loss of appetite and aversion to food until I'm back to my starting point. What options do I have here besides cannabis?

My philosophy is to base any additions on solid research, and to first do no harm. For that reason, I have over the past couple of years subtracted or reduced the dosage of many supplements that I had been taking on the basis of negative published research, even when the jury might still be out overall on a given supplement. Reduced or eliminated substances because of negative information or personal experience include but are not limited to ALA, CoQ10, all antioxidant megadosing, glucosamine, omega-3, arginine, ornithine, zinc, resveratrol, oral finasteride, dutasteride. I feel bad throwing stuff out so my fridge is a mess, unfortunately.

I am aware that the regimen may be overly conservative. Any comments are welcome.

Edited by andre, 28 January 2009 - 12:32 AM.

[pycnogenol]

Do you have any side effects taking Amitriptyline? I was taking amitriptyline for a time but switched to Pamelor.

Edited by pycnogenol, 28 January 2009 - 12:37 AM.

[nameless]

If you are getting most of your daily vits/minerals from diet, it looks good to me. I'm somewhat conservative regarding supplements too, although I take several things you aren't due to health reasons.

Things to consider:

A K2 supplement may not be a bad idea, as the K2 in Multi-Basics is somewhat skimpy. I take a half-dose of Multi-Basics myself, which is 60mcg of MK-4 (I think), so you are getting 40mcg at 1 cap/daily. Which is decent if the Rotterdam study is accurate... but it wouldn't hurt to throw in some MK-7 twice a week or so. Unless you enjoy eating Natto, which from what I've read, is kinda rare.

A little extra magnesium may not be bad either.

And your D3 may be too low. Have you had your D levels tested? You can't go by the RDA for D, as the RDA isn't accurate -- it varies too much person to person.

[nowayout]

Do you have any side effects taking Amitriptyline? I was taking amitriptyline for a time but switched to Pamelor.

No side effects that I notice at this dosage, which is very low compared to the dosage used for on-label purposes.

[nowayout]

A K2 supplement may not be a bad idea, as the K2 in Multi-Basics is somewhat skimpy. I take a half-dose of Multi-Basics myself, which is 60mcg of MK-4 (I think), so you are getting 40mcg at 1 cap/daily. Which is decent if the Rotterdam study is accurate... but it wouldn't hurt to throw in some MK-7 twice a week or so. Unless you enjoy eating Natto, which from what I've read, is kinda rare.

A little extra magnesium may not be bad either.

And your D3 may be too low. Have you had your D levels tested? You can't go by the RDA for D, as the RDA isn't accurate -- it varies too much person to person.

Thank you for the comments. I do seem to be getting more than the RDA of K and Magnesium from my diet already. Do you have any reasons in mind for taking more than that? I am not familiar with the Rotterdam study.

AS for D3, I should probably get tested. Until I can, a little moderation does not hurt, I guess. I'm old enough to remember (and to have participated in) the beta-carotene craze of the nineties. Once burned...

Edited by andre, 28 January 2009 - 12:51 PM.

[kismet]

• Glucosamine sulfate 500mg + Chondroitin sulfate 300mg + MSM 75 mg

So you are ingesting a substance at a dose with exactly zero positive data on it? 1500mg or 0mg glucosamine, there is no compromise which makes sense.
I don't think you should "probably" test vitamin D, you must test vitamin D if you want to find out whether your supplementation does any good (which it probably does not, because it's way too low for winter). If you don't test your blood levels it will just serve as an excuse to underdose vitamin D in the long term, which won't benefit anyone.

Thank you for the comments. I do seem to be getting more than the RDA of K and Magnesium from my diet already. Do you have any reasons in mind for taking more than that? I am not familiar with the Rotterdam study.

Does the CRONOmeter tell you which form of vitamin K you get? Phylloquinone is rather worthless as per the Rotterdam study (IIRC).

You could include cocoa and green tea as food supplements. The research I've seen so far is convincing.

Edited by kismet, 28 January 2009 - 01:25 PM.

[pycnogenol]

Andre,

Definitely get a vitamin D blood test. I get it done every 4 months so I can "dial in" the correct amount daily. I take 5,400 IU of D-3 per day.

[JLL]

I thought exercise was a pro-oxidant? Isn't that how hormesis works?

[nowayout]

• Glucosamine sulfate 500mg + Chondroitin sulfate 300mg + MSM 75 mg

So you are ingesting a substance at a dose with exactly zero positive data on it? 1500mg or 0mg glucosamine, there is no compromise which makes sense.

Well, yeah. You are probably right, but I have seen conflicting claims on this one. This is the one supplement I still take just in case it helps, at a dosage that is unlikely to do harm (to insulin metabolism).

I don't think you should "probably" test vitamin D, you must test vitamin D if you want to find out whether your supplementation does any good (which it probably does not, because it's way too low for winter).

Actually, it is not winter here, and I probably get enough sun exposure not to even need extra D.

Thank you for the comments. I do seem to be getting more than the RDA of K and Magnesium from my diet already. Do you have any reasons in mind for taking more than that? I am not familiar with the Rotterdam study.

Does the CRONOmeter tell you which form of vitamin K you get? Phylloquinone is rather worthless as per the Rotterdam study (IIRC).

No, it does not. I guess I'll have to research this some more.

You could include cocoa and green tea as food supplements. The research I've seen so far is convincing.

I do eat dark chocolate at the amounts that were found beneficial in a couple of studies I read, and I do drink various teas, including green and black tea. I did not include these as supplements since I consider them part of my regular diet. Are you talking about megadosing green tea extract? I remember looking into that but I had some concern about claims regarding its effect on androgen metabolism (for example, DHT inhibition, which I want to avoid).

[kismet]

I thought exercise was a pro-oxidant? Isn't that how hormesis works?

Hormesis, mh, isn't it thought to generally upregulate antioxidant defenses through oxidative/damaging (short term) processes? That's my simplistic understanding of the issue.

[nowayout]

I thought exercise was a pro-oxidant? Isn't that how hormesis works?

There is an increasing literature on this, and the fact that supplementing with too much antioxdants can block beneficial exercise adaptations. See for example pubmed 18191748. This is just one example I found by googling before I have to run, and there are studies in humans as well. You can also search imminst for some discussion of exercise and antioxidants.

Moderate exercise is an antioxidant: upregulation of antioxidant genes by training.
Gomez-Cabrera MC, Domenech E, Viña J.Department of Physiology, Faculty of Medicine, University of Valencia, Blasco Ibañez, 15, 46010 Valencia, Spain.

Exercise causes oxidative stress only when exhaustive. Strenuous exercise causes oxidation of glutathione, release of cytosolic enzymes, and other signs of cell damage. However, there is increasing evidence that reactive oxygen species (ROS) not only are toxic but also play an important role in cell signaling and in the regulation of gene expression. Xanthine oxidase is involved in the generation of superoxide associated with exhaustive exercise. Allopurinol (an inhibitor of this enzyme) prevents muscle damage after exhaustive exercise, but also modifies cell signaling pathways associated with both moderate and exhaustive exercise in rats and humans. In gastrocnemius muscle from rats, exercise caused an activation of MAP kinases. This in turn activated the NF-kappaB pathway and consequently the expression of important enzymes associated with defense against ROS (superoxide dismutase) and adaptation to exercise (eNOS and iNOS). All these changes were abolished when ROS production was prevented by allopurinol. Thus ROS act as signals in exercise because decreasing their formation prevents activation of important signaling pathways that cause useful adaptations in cells. Because these signals result in an upregulation of powerful antioxidant enzymes, exercise itself can be considered an antioxidant. We have found that interfering with free radical metabolism with antioxidants may hamper useful adaptations to training.

Edited by andre, 28 January 2009 - 06:59 PM.

[niner]

I don't think you should "probably" test vitamin D, you must test vitamin D if you want to find out whether your supplementation does any good (which it probably does not, because it's way too low for winter).

Actually, it is not winter here, and I probably get enough sun exposure not to even need extra D.

In that case, you should be using a good sunscreen, in which case you'll need the D anyway... I agree with everyone else; get tested. It's not very expensive, and it's too important to leave to chance. I would also consider 1000 IU to be a conservative dose, regardless of the season, without testing. It should be in an oil-based gelcap formulation. The dry formulations are not well absorbed.

[nameless]

Thank you for the comments. I do seem to be getting more than the RDA of K and Magnesium from my diet already. Do you have any reasons in mind for taking more than that? I am not familiar with the Rotterdam study.

AS for D3, I should probably get tested. Until I can, a little moderation does not hurt, I guess. I'm old enough to remember (and to have participated in) the beta-carotene craze of the nineties. Once burned...

Here is a link to the Rotterdam study for you:
http://jn.nutrition....ull/134/11/3100

K1, which is probably what you are mostly getting, doesn't convert to K2 so well in most people. If you are eating fancy cheeses or natto, you may be getting enough K2 already. But if getting K1 from greens, you might want to consider a little K2. Being conservative, a MK-7 supplement twice a week might be helpful. If not so conservative, take one daily, or a higher dose of MK-4 (in the gram range).

I suggest you do get your vitamin D levels checked, at least before winter comes. Although I'm not sure seasons matter as much as you think. During the summer I still tested deficient.

Other things to consider:

Pomegranate extract or juice may be a good idea, so long as you aren't taking any prescription medications that possibly could be affected by it.

Grapeseed and/or Pycnogenol have good data behind them too.

EGCG/green tea, if you don't drink it daily. I don't mean megadoses, just the equivalent of 3-4 cups daily. Although I can't take this advice myself, it seems, as I recently started a green tea extract and my stomach isn't cooperating so well. I think I'll have to stop it before my stomach slowly burns away...

[kismet]

• Glucosamine sulfate 500mg + Chondroitin sulfate 300mg + MSM 75 mg

So you are ingesting a substance at a dose with exactly zero positive data on it? 1500mg or 0mg glucosamine, there is no compromise which makes sense.

Well, yeah. You are probably right, but I have seen conflicting claims on this one. This is the one supplement I still take just in case it helps, at a dosage that is unlikely to do harm (to insulin metabolism).

I have only taken a short glance at the studies some time ago, but there is no conclusive evidence for any harm to insulin sensitivity/metabolism. I'd assume if there is any, it would be a linear response which means you are still doing damage, but at a dose which has never been demonstrated to help joint health whatsoever.
I think it's a waste of money more so than a health risk. Why do you take the chondroitin and MSM at such incredibly low doses too, which, I guess, never have been proven to do anything for joint health? Actually I'm convinced that the data on any dose of chondroitin is even bleaker than the data on high dose glucosamine (1500mg), which is already discouraging. I think you are wasting money.

I don't think you should "probably" test vitamin D, you must test vitamin D if you want to find out whether your supplementation does any good (which it probably does not, because it's way too low for winter).

Actually, it is not winter here, and I probably get enough sun exposure not to even need extra D.

I assumed that you live in a country where there are seasons, so even if it isn't winter now, I'm pretty sure winter will come. So try to keep the vitamin D in mind for the future. Although, I'd like to second niner, get a good sunscreen or do you know of any positive data on "plenty sunexposure" (a carcinogen as defined by the most conservative health bodies), which we have missed? It is even more important when using a retinoid.

If you are from the "pro-sun camp" I'd like to see some papers, because the position is rather rare these days and I'm interested to see any type of evidence.

You could include cocoa and green tea as food supplements. The research I've seen so far is convincing.

I do eat dark chocolate at the amounts that were found beneficial in a couple of studies I read, and I do drink various teas, including green and black tea. I did not include these as supplements since I consider them part of my regular diet. Are you talking about megadosing green tea extract? I remember looking into that but I had some concern about claims regarding its effect on androgen metabolism (for example, DHT inhibition, which I want to avoid).

No, with green tea I think it's good to stick to amounts supported by epidemiologic data (if megadosing, liver toxicity is possible in certain individuals, take care). "Megadosing" cocoa, though, is worth exploring in my opinion, but I haven't looked into any studies in enough detail (but I want to note that a recent life span study, with rather short lived rats, though, showed promising results for cocoa extracts).

I like your cautious approach, sounds like you have done a good job of researching your supplementation!

Edited by Michael, 18 May 2009 - 08:45 PM.

[nowayout]

Pomegranate extract or juice may be a good idea, so long as you aren't taking any prescription medications that possibly could be affected by it.

I have considered Pomegranate, but have not been able to figure out one way or another from the literature whether Pomegranate is in fact estrogenic or not. I have been avoiding it so far for this reason until I could find the time to research it again.

[davidd]

I don't think you should "probably" test vitamin D, you must test vitamin D if you want to find out whether your supplementation does any good (which it probably does not, because it's way too low for winter).

Actually, it is not winter here, and I probably get enough sun exposure not to even need extra D.

I assumed that you live in a country where there are seasons, so even if it isn't winter, I'm pretty sure winter will come. So try to keep the vitamin D in mind for the future. Although, I'd like to second niner, get a good sunscreen or do you know of any positive data on "plenty sunexposure" (a carcinogen as defined by the most conservative health bodies), which we have missed? It is even more important when using a retinoid.

If you are from the "pro-sun camp" I'd like to see some papers, because the position is rather rare these days and I'm interested to see any type of evidence.

I'm not in the "pro-sun camp" (if that means lots of sun exposure without sunscreen), and I haven't studied it to the Nth degree (since I am doing some other tests and won't be changing regimens for several months), but from what I did read, my understanding was that it only takes 5-10 minutes of sun exposure, of about 10% of your body, a few days per week, for most, non-obese caucasians to get in the "good" range of the vitamin D metabolite in their blood. People with darker skin would require longer exposures. The more fat you have, if I understand correctly, the longer exposure you would need and/or the more ingestion it would take of vitamin D to get to the "good" range, since the fat takes it out of the blood. I believe I also read that the vitamin D stored in fat could sustain the average person for a few months of reduced sun exposure. I'm not sure if that meant you could expect minimal levels, or if it would keep you in the "good" range. I'm also not sure if "average person" truly means average, which would mean people with a more than healthy amount of fat.

What I took out of this, for myself, was that I might be in the "good" range of serum levels in the summer in Minnesota, but would need supplementation (or artificial exposure) during the long winters (5-6 months of reduced exposure). I'm not overly fat, so I'm guessing I have less of an ability to store it up and use it later when sun exposure is reduced.

If I were to try to perfect my health, I would probably put on sunscreen after the 5-10 minutes of exposure. I don't have my lifestyle perfected to that degree, but I do often wear long pants and a shirt (short sleeves) and a hat, when I'm out in the garden in the summer (which is my main long-term sun exposure activity).

With all the variables that can affect the serum levels (where you live, air quality, what you wear, how long you are outside, skin pigmentation, fat levels, diet, time of year, etc.), my other take away is that the only way to truly know is to get tested periodically. That and that I need to determine what the "good" range truly is, since recommendations vary widely on this topic.

Ponderings... I wonder what effect the obese issue will have on the general population as it relates to vitamin D? I mean, how much will this aspect alone contribute to health issues of the obese?

David

[nowayout]

I assumed that you live in a country where there are seasons, so even if it isn't winter now, I'm pretty sure winter will come. So try to keep the vitamin D in mind for the future. Although, I'd like to second niner, get a good sunscreen or do you know of any positive data on "plenty sunexposure" (a carcinogen as defined by the most conservative health bodies), which we have missed? It is even more important when using a retinoid.

No evidence here except subjective experience. First, I am as keen to avoid sun-damage as everyone else here. Obviously I avoid all sun exposure on my face and neck (where I use the retinoid). Then, there is obviously a big difference in degree of damage between getting a lot of exposure on a small area (on which some of the recommendations for vitamin D production I have read were based) and getting just a little exposure on a large area. I do at most five to ten minutes every week or two each side over the whole torso and legs. This is causes no visible burning or tanning and seems to bring health benefits beyond what I can straightforwardly explain by vitamin D production. These benefits include dramatically better mood, less anxiety, probably lower blood pressure, and better libido, and they last at least a week. I have yet to hear people reporting these kinds of dramatic effects from vitamin D supplementation. I therefore do not think we know all there is to know about the physiological effects of sun exposure.

I do spend part of my year in the New England winter, where I have been known to use (gasp!) a sunbed in an emergency. Again, I go for about three minutes to avoid too much damage. In my case this is a life-extending intervention, since it stops me from killing myself.

I am also keen to avoid the problem of my grandmother and my father, who have avoided sun exposure all their lives, as a result of which they have developed an allergic reaction (hives, itching) from any incidental exposure.

[kismet]

I'm not in the "pro-sun camp" (if that means lots of sun exposure without sunscreen), and I haven't studied it to the Nth degree (since I am doing some other tests and won't be changing regimens for several months), but from what I did read, my understanding was that it only takes 5-10 minutes of sun exposure, of about 10% of your body, a few days per week, for most, non-obese caucasians to get in the "good" range of the vitamin D metabolite in their blood.

With some limitations as you will see when you read Holick's paper [1]. Most importantly the ability of vitamin D synthesis declines with age.

People with darker skin would require longer exposures. The more fat you have, if I understand correctly, the longer exposure you would need and/or the more ingestion it would take of vitamin D to get to the "good" range, since the fat takes it out of the blood. I believe I also read that the vitamin D stored in fat could sustain the average person for a few months of reduced sun exposure. I'm not sure if that meant you could expect minimal levels, or if it would keep you in the "good" range. I'm also not sure if "average person" truly means average, which would mean people with a more than healthy amount of fat.

Vitamin D is only stored if it reaches 40-50ng/L according to Dr. Cannel from the vitamin D council website.

What I took out of this, for myself, was that I might be in the "good" range of serum levels in the summer in Minnesota, but would need supplementation (or artificial exposure) during the long winters (5-6 months of reduced exposure). I'm not overly fat, so I'm guessing I have less of an ability to store it up and use it later when sun exposure is reduced.

If I were to try to perfect my health, I would probably put on sunscreen after the 5-10 minutes of exposure. I don't have my lifestyle perfected to that degree, but I do often wear long pants and a shirt (short sleeves) and a hat, when I'm out in the garden in the summer (which is my main long-term sun exposure activity).

That's strange, you were bothered by the inconclusive data on glucosamine and insulin metabolism, but the more conclusive data on sun and cancer does not bother you? From reading your regimen I thought you are perfectionist.

With all the variables that can affect the serum levels (where you live, air quality, what you wear, how long you are outside, skin pigmentation, fat levels, diet, time of year, etc.), my other take away is that the only way to truly know is to get tested periodically. That and that I need to determine what the "good" range truly is, since recommendations vary widely on this topic.

Ponderings... I wonder what effect the obese issue will have on the general population as it relates to vitamin D? I mean, how much will this aspect alone contribute to health issues of the obese?

David

53.4-71.2ng/mL vs <17.8ng/mL reduces all-cause mortality. [2]
Other (mostly retrospective) studies have shown consistently better outcomes with higher levels of vitamin D too. At the very, very least you should aim for >30ng or maybe even more like >50ng/mL, basically every sane vitamin D expert proposes at least 30-60ng/mL (e.g. Cannel, Holick, Zitterman).
You should read Holick's paper [1] and/or the vitamin D council's page on toxicity. As of now there's no reason to worry about overdosing, whereas the risk of deficiency is real.

I assumed that you live in a country where there are seasons, so even if it isn't winter now, I'm pretty sure winter will come. So try to keep the vitamin D in mind for the future. Although, I'd like to second niner, get a good sunscreen or do you know of any positive data on "plenty sunexposure" (a carcinogen as defined by the most conservative health bodies), which we have missed? It is even more important when using a retinoid.

No evidence here except subjective experience. First, I am as keen to avoid sun-damage as everyone else here. Obviously I avoid all sun exposure on my face and neck (where I use the retinoid). Then, there is obviously a big difference in degree of damage between getting a lot of exposure on a small area (on which some of the recommendations for vitamin D production I have read were based) and getting just a little exposure on a large area.

No, not according to the accepted linear no-threshold model (LNT), which says that any radiation is damaging and the response is linear. But maybe only radiation hormesis correctly explains low dose exposure (still debated). It should be worth looking into, if you like to get some sun exposure.

I do at most five to ten minutes every week or two each side over the whole torso and legs. This is causes no visible burning or tanning and seems to bring health benefits beyond what I can straightforwardly explain by vitamin D production. These benefits include dramatically better mood, less anxiety, probably lower blood pressure, and better libido, and they last at least a week. I have yet to hear people reporting these kinds of dramatic effects from vitamin D supplementation. I therefore do not think we know all there is to know about the physiological effects of sun exposure.

I think you are talking about seasonal affective disorder (SAD) or something similar? As far as I know the treatments are dependant on brightness and not damaging UV rays.
Besides it is known that sun exposure prompts a release of endorphins, which might explain your results too, but there exist other ways to get an endorphin release.
Those are the two known vitamin D independent aspects of sun exposure. Interestingly Holick himself is a proponent of minimal sun exposure, he even published a book "The UV Advantage". On the other hand one can argue that it's easier to sell a book about sun exposure, than to sell supplementation and blood testing.

[1]Sunlight and vitamin D for bone health and prevention of autoimmune diseases, cancers, and cardiovascular disease.
Holick MF.
"Vitamin D deficiency is an unrecognized epidemic among both children and adults in the United States."
http://www.ajcn.org/...full/80/6/1678S
[2]Arch Intern Med. 2008 Aug 11;168(15):1629-37.
25-hydroxyvitamin D levels and the risk of mortality in the general population.
Melamed ML, Michos ED, Post W, Astor B.
Am J Clin Nutr. 2004 Dec;80(6 Suppl):1678S-88S.

Edited by kismet, 01 February 2009 - 01:23 PM.

[nowayout]

...

Thank you. That is some good information.

[davidd]

With all the variables that can affect the serum levels (where you live, air quality, what you wear, how long you are outside, skin pigmentation, fat levels, diet, time of year, etc.), my other take away is that the only way to truly know is to get tested periodically. That and that I need to determine what the "good" range truly is, since recommendations vary widely on this topic.

Ponderings... I wonder what effect the obese issue will have on the general population as it relates to vitamin D? I mean, how much will this aspect alone contribute to health issues of the obese?

David

53.4-71.2ng/mL vs <17.8ng/mL reduces all-cause mortality. [2]
Other (mostly retrospective) studies have shown consistently better outcomes with higher levels of vitamin D too. At the very, very least you should aim for >30ng or maybe even more like >50ng/mL, basically every sane vitamin D expert proposes at least 30-60ng/mL (e.g. Cannel, Holick, Zitterman).
You should read Holick's paper [1] and/or the vitamin D council's page on toxicity. As of now there's no reason to worry about overdosing, whereas the risk of deficiency is real.

Your numbers jive with what my brain remembers from when I looked into Vitamin D. I did read a lot on the Vitamin D council's website in the past. I think may have post about that in another thread on imminst -- probably related to William's and/or Larry's cancer regimens. I am thinking my past researched showed that you'd want to keep the level to under 100 ng/mL, for reasons of toxicity. Of course, that allows for quite a range and as you show above, even the experts propose a range that varies by 100% from the low to the top end.

I remember seeing a graph that showed that all cause mortality started increasing again after 40 ng/ml. Not as great as lower than 30, but still something to keep in mind if it is true.

The other missing pieces for me are how much magnesium and calcium should be taken when vitamin D levels are increased. Do you have any research to share on that topic?

Thanks,
David

Edited by Michael, 18 May 2009 - 08:47 PM.
Redundant discussion of corrected confusion

[kismet]

Your numbers jive with what my brain remembers from when I looked into Vitamin D. I did read a lot on the Vitamin D council's website in the past. I think may have post about that in another thread on imminst -- probably related to William's and/or Larry's cancer regimens. I am thinking my past researched showed that you'd want to keep the level to under 100 ng/mL, for reasons of toxicity. Of course, that allows for quite a range and as you show above, even the experts propose a range that varies by 100% from the low to the top end.

I remember seeing a graph that showed that all cause mortality started increasing again after 40 ng/ml. Not as great as lower than 30, but still something to keep in mind if it is true.

The other missing pieces for me are how much magnesium and calcium should be taken when vitamin D levels are increased. Do you have any research to share on that topic?

Interesting, which study features this graph? Unfortunately, I can't access the epidemiologic study which I quoted, but it's the most recent/complete as far as I know. I did not research the connection between calcium vitamin D yet, but I may look into it in the future. Vitamin D increases calcium availability and I am not aware of any positive data on supraphysiologic doses of calcium, so maybe one should stick with moderate-high calcium intake -- I guess.

Edited by Michael, 18 May 2009 - 08:47 PM.

[davidd]

Your numbers jive with what my brain remembers from when I looked into Vitamin D. I did read a lot on the Vitamin D council's website in the past. I think may have post about that in another thread on imminst -- probably related to William's and/or Larry's cancer regimens. I am thinking my past researched showed that you'd want to keep the level to under 100 ng/mL, for reasons of toxicity. Of course, that allows for quite a range and as you show above, even the experts propose a range that varies by 100% from the low to the top end.

I remember seeing a graph that showed that all cause mortality started increasing again after 40 ng/ml. Not as great as lower than 30, but still something to keep in mind if it is true.

The other missing pieces for me are how much magnesium and calcium should be taken when vitamin D levels are increased. Do you have any research to share on that topic?

Thanks,
David

Interesting, which study features this graph? Unfortunately, I can't access the epidemiologic study which I quoted, but it's the most recent/complete as far as I know. I did not research the connection between calcium vitamin D yet, but I may look into it in the future. Vitamin D increases calcium availability and I am not aware of any positive data on supraphysiologic doses of calcium, so maybe one should stick with moderate-high calcium intake -- I guess.

I founy my post where I gave some links to some of my sources of information. That may be a starting point for the magnesium and calcium relationships. As I state in that post, I believe I read that more calcium is needed when taking high amounts of vitamin D, as the vitamin D is supposed to push the calcium into the bones, possibly not leaving as much in the blood. Same goes for suddenly stopping high vitamin D dosing, as it may pull too much calcium out of the bones too quickly. Feel free to double check my memory on this, however.

Lastly, the other thing I forgot to mention in our discourse is the vitamin A relationship. I think that warrants more study of the latest research.

Here is what I said in that post about calcium and magnesium:

...
One of those links I gave discussed taking 800-1200 mg of calcium and 400-600 mg of magnesium. But I think the amount would need to be adjusted based on how much Vitamin D you are taking. I don't know how to do this adjustment.
...

One of the things I worry about with dramatically increasing doses of some supplements is the effect is has on other chemicals that work synergistically/symbiotically.



I hunted a while to find that U-shaped graph showing mortality increasing at both ends of vitamin D dosing. Success! See the attachment and the link to the page where I found it:

http://courses.washi...hys/opvitD.html






Seems like the sweet spot is 30-40 range. Of course, it could also be that people higher than 40 ng/ml were not maintaining the proper balance of other things that tie in with Vitamin D. It could also be that those people had higher vitamin D due to a lot of sun exposure and died from related issues. I don't know...just pointing out the old, "correlation doesn't equal causality" concept. It is theoretically possible that if we countered a number of other issues through other means *and* kept our levels at 40-60, we could live longer than the people in the study. We just need to find what those other "issues" might be.

If we use the line that they fit to the distributed data, then I'd much rather be at the 60 end than the below 20 end, if I were to error one way or the other.

If I had to pick, right this moment, I'd personally go with a level of 40 ng/ml. Before I increase my vitamin D intake to achieve this (if testing shows it to be lower), I'll need to figure out the calcium, magnesium and vitamin A levels that should accompany it.

David

[kismet]

Wow, that's an interesting graph. It does not paint a nice picture for Cannell's >50ng/mL target, as the lowest mortality seems to be in the mid 30s. However, there might be some limitations to this study. If only <3% people reach higher than 50ng/mL as shown in a graph from another study, on the same site, it would weaken any such conclusions. And if people rarely reach that high levels, who does? If you tan skin cancer may offset the benfits of vitamin D, if you are sick you may supplement with high doses of vitamin D, which again leads us to the limitations of epidemiologic research.
I'm sure Cannell's >50ng/mL target is based on solid evidence, but all-cause mortality is probably still most interesting to life extensionists. Higher blood levels of vitamin D may require some trade-offs.
I'd like Krillin or some other "vitamin D expert" to comment...

[davidd]

Wow, that's an interesting graph. It does not paint a nice picture for Cannell's >50ng/mL target, as the lowest mortality seems to be in the mid 30s. However, there might be some limitations to this study. If only <3% people reach higher than 50ng/mL as shown in a graph from another study, on the same site, it would weaken any such conclusions. And if people rarely reach that high levels, who does? If you tan skin cancer may offset the benfits of vitamin D, if you are sick you may supplement with high doses of vitamin D, which again leads us to the limitations of epidemiologic research.
I'm sure Cannell's >50ng/mL target is based on solid evidence, but all-cause mortality is probably still most interesting to life extensionists. Higher blood levels of vitamin D may require some trade-offs.
I'd like Krillin or some other "vitamin D expert" to comment...

I don't remember where I read it (may have been in one of those links I gave), but they said that surfers were studied and they reached a maximum level of 60. I think that's where some of the higher levels (50-60) from the experts come from. They are relying on the fact that mother nature put in an automatic limiter at 60, for some reason. That does have some compelling logic behind it.

However, mother nature may not have cut us off *right* at the amount that allows for the longest lifespan. She might have cut us off at the limit that allowed us to live long enough to serve a certain purpose (or purposes). So, thinking of it that way and looking at that graph and assuming they do have enough people at the high end to make it statistically significant, I think I'm still near 40 for my best guess.

Yes, I'd love to hear anyone else's analysis of this.

David

[niner]

Wow, that's an interesting graph. It does not paint a nice picture for Cannell's >50ng/mL target, as the lowest mortality seems to be in the mid 30s. However, there might be some limitations to this study. If only <3% people reach higher than 50ng/mL as shown in a graph from another study, on the same site, it would weaken any such conclusions. And if people rarely reach that high levels, who does? If you tan skin cancer may offset the benfits of vitamin D, if you are sick you may supplement with high doses of vitamin D, which again leads us to the limitations of epidemiologic research.
I'm sure Cannell's >50ng/mL target is based on solid evidence, but all-cause mortality is probably still most interesting to life extensionists. Higher blood levels of vitamin D may require some trade-offs.
I'd like Krillin or some other "vitamin D expert" to comment...

I don't remember where I read it (may have been in one of those links I gave), but they said that surfers were studied and they reached a maximum level of 60. I think that's where some of the higher levels (50-60) from the experts come from. They are relying on the fact that mother nature put in an automatic limiter at 60, for some reason. That does have some compelling logic behind it.

If the mortality curve is based on surfers at the high end, that would pretty much explain it. I would want to see the "all-cause" broken down into sub-categories, because if at the high end of the D scale, it's overloaded with auto accidents, drowning, and alcohol overdose, then I'm not too worried about it.

[davidd]

Wow, that's an interesting graph. It does not paint a nice picture for Cannell's >50ng/mL target, as the lowest mortality seems to be in the mid 30s. However, there might be some limitations to this study. If only <3% people reach higher than 50ng/mL as shown in a graph from another study, on the same site, it would weaken any such conclusions. And if people rarely reach that high levels, who does? If you tan skin cancer may offset the benfits of vitamin D, if you are sick you may supplement with high doses of vitamin D, which again leads us to the limitations of epidemiologic research.
I'm sure Cannell's >50ng/mL target is based on solid evidence, but all-cause mortality is probably still most interesting to life extensionists. Higher blood levels of vitamin D may require some trade-offs.
I'd like Krillin or some other "vitamin D expert" to comment...

I don't remember where I read it (may have been in one of those links I gave), but they said that surfers were studied and they reached a maximum level of 60. I think that's where some of the higher levels (50-60) from the experts come from. They are relying on the fact that mother nature put in an automatic limiter at 60, for some reason. That does have some compelling logic behind it.

If the mortality curve is based on surfers at the high end, that would pretty much explain it. I would want to see the "all-cause" broken down into sub-categories, because if at the high end of the D scale, it's overloaded with auto accidents, drowning, and alcohol overdose, then I'm not too worried about it.

That particular curve was not related to the study on surfers. However, I agree about wanting to see the causes of death. They usually try to exclude the other types of death, or at least normalize for them. Although alcohol abuse may slip through the cracks and other things like that may be unknown. I think the best way to rule those out is to have plenty of people along the full length of the graph. This study had a lot of people in it, but we don't know the distribution. I think they would have put a disclaimer on the graph if it was heavily weighted on the left side, but since it was not pulled from the original study, I can't say for sure.

Now, if I look at your reply a different way, then good joke.

David

[niner]

Here is the original paper that was the source of the U-shaped all-cause mortality curve. I'm not sure exactly what to make of the fact that the CVD and cancer models weren't statistically significant. I presume the causes of death at the higher end of the curve are cancer and CVD given the data source, but would like to hear the author's interpretation of the role of vitamin D in those deaths. Anyone have access to the full text of the paper?

Arch Intern Med. 2008 Aug 11;168(15):1629-37. Link to Full Text, Not Free.
25-hydroxyvitamin D levels and the risk of mortality in the general population.

Melamed ML, Michos ED, Post W, Astor B.

Division of Nephrology, Department of Medicine, Albert Einstein College of Medicine, 1300 Morris Park Ave, Ullmann 615, Bronx, NY 10461, USA. mmelamed@aecom.yu.edu

BACKGROUND: In patients undergoing dialysis, therapy with calcitriol or paricalcitol or other vitamin D agents is associated with reduced mortality. Observational data suggests that low 25-hydroxyvitamin D levels (25[OH]D) are associated with diabetes mellitus, hypertension, and cancers. However, whether low serum 25(OH)D levels are associated with mortality in the general population is unknown. METHODS: We tested the association of low 25(OH)D levels with all-cause, cancer, and cardiovascular disease (CVD) mortality in 13 331 nationally representative adults 20 years or older from the Third National Health and Nutrition Examination Survey (NHANES III) linked mortality files. Participant vitamin D levels were collected from 1988 through 1994, and individuals were passively followed for mortality through 2000. RESULTS: In cross-sectional multivariate analyses, increasing age, female sex, nonwhite race/ethnicity, diabetes, current smoking, and higher body mass index were all independently associated with higher odds of 25(OH)D deficiency (lowest quartile of 25(OH)D level, <17.8 ng/mL [to convert to nanomoles per liter, multiply by 2.496]), while greater physical activity, vitamin D supplementation, and nonwinter season were inversely associated. During a median 8.7 years of follow-up, there were 1806 deaths, including 777 from CVD. In multivariate models (adjusted for baseline demographics, season, and traditional and novel CVD risk factors), compared with the highest quartile, being in the lowest quartile (25[OH]D levels <17.8 ng/mL) was associated with a 26% increased rate of all-cause mortality (mortality rate ratio, 1.26; 95% CI, 1.08-1.46) and a population attributable risk of 3.1%. The adjusted models of CVD and cancer mortality revealed a higher risk, which was not statistically significant. CONCLUSION: The lowest quartile of 25(OH)D level (<17.8 ng/mL) is independently associated with all-cause mortality in the general population.

PMID: 18695076

[kismet]

Anyone have access to the full text of the paper?

Yes, I want that paper too, it's the one I can't access. Davidd, Holick for instance notes that sunbathers and lifeguards reach not 60ng/mL, but up to 100ng/mL without evidence of toxicity and no hardwired limit at 60ng. Cannell emphasises that toxicity starts only at 150ng/mL (rarely there are reports of tox. at >=80ng/mL). Any issues with >50ng/mL must be subtle and I am wondering why Cannell's target is >50ng/mL and Holick's >30ng/mL? I can't find the paper where Cannell mentioned that ~50ng/mL are necessary for optimal bone health...

Edited by kismet, 02 February 2009 - 02:12 PM.

[kismet]

...
The other missing pieces for me are how much magnesium and calcium should be taken when vitamin D levels are increased. Do you have any research to share on that topic?

Thanks,
David

Other interesting notes, Vitamin A toxicity, possibly through Vitamin D antagonism (important if supplementing Vitamin A but not enough D, like with any cheap multi). http://www.vitamindc...-december.shtml

One of the studies trying to determine an optimal Vitamin D level, using a very interesting approach (Hollis is another top vitamin D researcher):

J Steroid Biochem Mol Biol. 2007 Mar;103(3-5):631-4. Epub 2007 Jan 10.
Circulating vitamin D3 and 25-hydroxyvitamin D in humans: An important tool to define adequate nutritional vitamin D status.
Hollis BW, Wagner CL, Drezner MK, Binkley NC.
http://www.pubmedcen...bmedid=17218096
"Optimal nutritional vitamin D status may occur when approaching equimolar concentrations of circulating vitamin D3 and 25(OH)D (>100 nmol). At this point, the Vmax of the enzyme appears to be achieved. It is important to note that as humans live today, the vitamin D-25-hydroxylase operates well below its Vmax because of chronic substrate (vitamin D) deficiency. Not a single other steroidal hormone system in the body is limited in this fashion since their starting point is cholesterol. When humans are sun- (or dietary-) replete, the vitamin D endocrine system will function in a fashion as do these other steroid synthetic pathways, not limited by substrate availability."

And I think Cannell has found some evidence for people needing up to 50ng/mL for optimal (muscular) performance. So I like to say "Vitamin D the strongest secosteroid known to man, even stronger than methyltrienolon (metribolon)!".. Maybe optimal performance leads to slightly increased mortality (still lower than with a deficiency)? Or maybe the epidemiologic research cannot be trusted in this regard?
One of the most impressive reviews by him, vitamin d and athletic performance.
EDIT: corrected URL to the athletic performance review

EDIT: another possible explanation for high levels being "bad", although I am not sure in how far it is supported by actual data and not just a mechanistic explanation:
"Vieth's [the first researcher to recognise "vitamin D toxicity" is blown out of proportion] explanation that high levels put one at risk because such patients do not maintain them throughout the year. Vitamin D levels fall precipitously in the autumn and winter, triggering even lower intracellular levels. It appears that falling levels may be as dangerous as low levels"

Edited by kismet, 04 February 2009 - 01:29 PM.

[kismet]

Interestingly Cannell is in the "sensible sun exposure" camp like Holick. He acknowledges the fact that sun exposure is unmistakeably correlated with skin aging and non-melanoma skin cancers, but probably not with melanoma (I am not sure what the current data says?), but he still advises sun exposure. I think he is wrongly assuming that science first needs to disprove the benefits of sun exposure until then we should recommend it, maybe because "our ancestors developed in the sun" (certainly a fallacy, if there is no supporting data). Personally I'm quite sure science needs to prove the vitamin D independent benefits of sun exposure first, not the other way round!

Yes, as already discussed in this thread there may be some benefits, but I believe they are limited to brightness regulating melatonin production and possible endorphin releases from sun exposure.

I am certainly not aware of all the data, but I'm pretty sure that sun avoidance and vitamin D supplementation are prudent - for most people. Maybe I really need to buy Holick's book and dig up some studies supporting their stance... I believe through evolution we have in part turned a liability - ionizing and in the long term damaging UVB radiation - into an asset i.e. vitamin D synthesis, so as not to waste any internal resources on vitamin D synthesis. Definitely a great plan for short lived paleo man, but what about us?

Cannell vs dermatology: http://www.vitamindc.../2006-feb.shtml

Edited by kismet, 02 February 2009 - 03:33 PM.