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123 Days PF And I Think I know Why (Read 446818 times)
Peter510
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Re: 123 Days PF And I Think I know Why
Reply #2125 - Jan 19th, 2015 at 11:14am
 
Hi folks,
Update: day 10, first pain free 24 hours in almost two years.. Amazing feeling, long may it continue!!!!!!
No blood results yet. But should have that at the end of the week.

Note to: getoutofmyhead. There are better guys than me on here who can explain the dosage, but Thierry sent this to me regarding where you can buy. Multimedia File Viewing and Clickable Links are available for Registered Members only!!  You need to Login or Register
Hope this helps.
Peter.
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Re: 123 Days PF And I Think I know Why
Reply #2126 - Jan 19th, 2015 at 1:53pm
 
Hey Littlee,

Sorry I missed your question... Go ahead and take the 50,000 IU loading dose now. 

The metrics of this regimen are 600,000 IU vitamin D3 over 4 weeks.  You can compress the schedule and do 600,000 IU vitamin D3 in two or three weeks then drop back to a maintenance dose of 10,000 IU/day.  Try to get another lab test for you 25(OH)D and PTH at that time.

Take care and please keep us posted.

V/R, Batch
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Re: 123 Days PF And I Think I know Why
Reply #2127 - Jan 19th, 2015 at 2:07pm
 
Getoutofmyhead,

Try to see you PCP or neurologist for a lab test of your 25(OH)D.  If that looks like it's going to take more than a few days, go ahead and start the anti-inflammatory regimen but be sure to get tested after taking it for a month.

The normal reference range of 25(OH)D is 30 to 100 ng/mL.  However, most physicians will interpret 31 ng/mL as normal.  While that may be true and a high enough concentration to prevent rickets... it's far too low to prevent CH.  CH'ers need to have their 25(OH)D up in a range between 60 to 110 ng/mL (The target 25(OH)D serum concentration is 80 ng/mL).

Over the last four years at least 600 cluster headache sufferers (CH'ers) have started the anti-inflammatory regimen of vitamins and minerals with at least 10,000 IU/day vitamin D3. 

83% of them have experienced a significant reduction in the frequency, severity and duration of their CH.  75% experienced multiple 24-hour pain free periods and 60% remain essentially pain free.  This regimen is equally effective for episodic and chronic CH'ers.  This regimen is also effective for Migraineurs in preventing their headaches.

The "Go To" link with info on all the anti-inflammatory supplements, their doses, drug interactions and contraindications follows:

Multimedia File Viewing and Clickable Links are available for Registered Members only!!  You need to Login or Register

The following table represents the latest list of anti-inflammatory regimen supplements and doses:

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I've found the following supplements shown by brand in the photo below are formulated with most of the supplements we need.  I buy them at Costco, but you should be able to find similar formulations at most Vitamin Shoppes, supermarkets, Wall-Mart or over the Internet:

Multimedia File Viewing and Clickable Links are available for Registered Members only!!  You need to Login or Register

The vitamin B 50 is not shown.  You’ll need a 3-month course of vitamin B 50 to handle any deficiencies among the seven B vitamins. 

If you can’t get to a Costco outlet, Thierry, a CH’er in Ireland, has posted a source for all the needed supplements at iherb.com.  See his post at the following link for details on how to order them over the Internet:

Multimedia File Viewing and Clickable Links are available for Registered Members only!!  You need to Login or Register

Although the Super K with vitamin K2 complex isn't essential in preventing CH, it is needed to handle the increased serum calcium made available by taking vitamin D3 at the doses we take.

There are a growing number of studies finding the super K2 complex helps direct calcium away from soft tissues and arteries directing it instead to bones and teeth improving overall bone mineral density.

There are also a number of studies that have addressed the optimum ratio of calcium-magnesium supplements.  The general consensus is to keep these two supplements at a 2:1 ratio.  Many have found 400 mg/day sufficient.

Most CH'ers who have started this regimen over the last year and had their 25(OH)D results come back below 30 ng/mL, have used the accelerated vitamin D3 dosing schedule and found it got them pain free faster than taking the maintenance dose of vitamin D3 at 10,000 IU/day...  The accelerated vitamin D3 dosing schedule follows:

On day one, take the entire regimen with 10,000 IU/day vitamin D3 and two of the Omega-3 Fish Oil liquid softgel capsules along with one each of the remaining supplements the first day.

If there's no allergic reaction to these supplements (very rare), take 20,000 IU/day vitamin D3 for the next two weeks along with the rest of the regimen.

In addition, for the first two weeks take a 50,000 IU loading dose (ten of the 5,000 IU vitamin D3 softgels) once a week on top of the daily dose for two weeks.  The day of the loading dose you'll be taking a total of 70,000 IU vitamin D3.

After two weeks on above vitamin D3 dosing schedule, stop taking the once a week loading dose and lower your daily vitamin D3 intake to 15,000 IU/day. Continue at this dose for another two weeks then lower the vitamin D3 intake to a maintenance dose of 10,000 IU/day.  At that point see your PCP for another lab test for 25(OH)D.

If you total the vitamin D3 doses you'll be taking 600,000 IU vitamin D3 over the 4 week period.  This should elevate your 25(OH)D serum concentration by 60 ng/mL, (150 nmol/L) above your starting level.  Assuming that starting level was less than 30 ng/mL, (75 nmol/L), your serum concentration should be around 85 ng/mL, (212 nmol/L).

If you're like most of the other CH'ers who start this regimen, you'll experience a favorable response within the first week to ten days.  Migraineurs sail through their usual cycle times with nary a twinge...

Regarding the safety of this regimen.  Long term dosing with 10,000 IU/day vitamin D3 is very safe.  Depending on skin type, our skin can make 15,000 IU of vitamin D3 in as little as 10 minutes if exposed to the UV-B in direct mid-day sunlight clad in a bathing suit without any sun block. 

There haven’t been any posts or reports of vitamin D3 intoxication or any adverse reactions requiring medical attention since I started posing about  this regimen in December of 2010. 

If you have questions please sing out.

Again, the above regimen of vitamins and minerals is called the anti-inflammatory regimen.  At 30 to 45 cents a day, depending on where you buy your supplements, this is the most cost effective and safest CH preventative available to us. You can read all about it at the following links:

Multimedia File Viewing and Clickable Links are available for Registered Members only!!  You need to Login or Register.

Multimedia File Viewing and Clickable Links are available for Registered Members only!!  You need to Login or Register

Multimedia File Viewing and Clickable Links are available for Registered Members only!!  You need to Login or Register

Take care and please keep us posted.

V/R, Batch.

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« Last Edit: Jan 19th, 2015 at 2:08pm by Batch »  

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thierry
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Re: 123 Days PF And I Think I know Why
Reply #2128 - Jan 20th, 2015 at 7:20am
 
Hi Peter, I am so delighted for you after reading your last post. Being PF is something we could only have dreamt of.... until we read this thread and Batch's regimen.
Next we can look at where to get your regimen's supplements at a more affordable price.
I am sure your a savouring your PF life.
All the best.
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« Last Edit: Jan 20th, 2015 at 3:11pm by thierry »  
 
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Peter510
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Re: 123 Days PF And I Think I know Why
Reply #2129 - Jan 20th, 2015 at 9:50am
 
Thierry,

Spoke a little too soon. Got one hit at 3:30 this morning. 7/8 which lasted about 20 minutes. Nothing since, so its definitely an imorovement, but I got a bit excited yesterday when I posted.
I'll exercise a bit more caution and continue taking the Vits.
Cheers,
peter.
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Re: 123 Days PF And I Think I know Why
Reply #2130 - Jan 20th, 2015 at 10:26am
 
Peter, it will get better. Wise to continue the loading doses so that you achieve 600000 iu D3 in the first month as stated above by Batch.
All the best
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Peter510
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Re: 123 Days PF And I Think I know Why
Reply #2131 - Jan 24th, 2015 at 10:05am
 
Hey folks,
Update on D3 programme two weeks in. Some small change in severity and frequency, but nothing I could say is momentous. Got the blood results and my D3 level was 33. That was after 5 days into the regimen.
So on we go. It will be interesting to see how the next two weeks go and how the blood level increases.
Keep well,
Peter
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Re: 123 Days PF And I Think I know Why
Reply #2132 - Jan 24th, 2015 at 4:23pm
 
Peter, 33 nm/ol is very low, the therpeutic level of D3 is around 200 nm/ol for us CH'ers.
Did you try Zomig? you GP can prescribe it, it works, you could take that when you get a bad attack until your D3 levels are up.
all the best
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Re: 123 Days PF And I Think I know Why
Reply #2133 - Jan 24th, 2015 at 6:59pm
 
Peter,

Check your PM inbox at the top left corner of this screen.  I've sent you a suggested vitamin D3 loading schedule you'll need to discuss with your PCP or neurologist.

Shoot me a PM if you have questions.

Take care,

V/R, Batch
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Re: 123 Days PF And I Think I know Why
Reply #2134 - Jan 24th, 2015 at 7:52pm
 
Below from vitamindcouncil.org (not the first bit that's mine)

Thanks to my headaches I have been spending what should have been sleep time researching and I can tell you what I have come up with is curing headaches is a Black Art.

Most meds have been developed for other purposes many psychiatric drugs, anti fitting and even weirder stuff, the rule seems to be if it works for one then try it on someone else.

Some developed for headache meds list headaches as a side effect, some meds work completely differently in different people and oral meds can be neutralised in some peoples stomach's.

Blood pressure meds compete with the brain's requirements, BP meds can work to relax the blood vessels and expand them whilst the brain wants then kept constricted.

Then you get onto the clever chemistry and stuff about emitters and receptors and the cheery admission by the experts  that they don't know how they work and if they don't they don't no why either.

The brain is billions of times more complicated than the cleverest computers so its not surprising that a definitive solution to a specific problem is often only arrived at by trial and error.

We know people get addicted to some meds that do their headaches no goog whatsoever but those who have witnessed first hand the impossible to describe agony of the cluster / cluster type headache are fully sympathetic to someone who tries anything just to make the pain go away.

Which brings me to Batch;'s Regimen, it has obviously worked for some, apparenty a vast majority of those who have tried it but here's the thing; is it safe? what is the science behind it and what are the chemical / neurotransmitter responses on specific cells and receptors, what conflicts are set up.

Don't get me wrong the traditional and licensed meds don't offer the answers to these questions and as I say if it works who gives a damn.

I'm tempted to put a paper together on some of the stranger things my research has taught me but until then here is the Vitamin D Councils offering on too much vit D

Am I getting too much vitamin D?

Although most people take vitamin D supplements without any problems, it’s possible to take too much. This is called vitamin D toxicity. Vitamin D toxicity, where vitamin D can be harmful, usually happens if you take 40,000 IU per day for a couple of months or longer, or take a very large one-time dose.

Vitamin D is fat-soluble, which means your body has a hard time getting rid of it if you take too much. When you take large amounts of vitamin D, your liver produces too much of a chemical called 25(OH)D.

When your 25(OH)D levels are too high, this can cause high levels of calcium to develop in your blood. High blood calcium is a condition called hypercalcemia.

The symptoms of hypercalcemia include:

    feeling sick or being sick
    poor appetite or loss of appetite
    feeling very thirsty
    passing urine often
    constipation or diarrhea
    abdominal pain
    muscle weakness or pain
    feeling confused
    feeling tired

In some rare diseases, you may be at risk of hypercalcemia even if you have low vitamin D levels and haven’t taken much vitamin D. These diseases include primary hyperparathyroidism, sarcoidosis and a few other rare diseases. See our Hypersensitivity page page for more information.
How do I know if I have taken too much?

A blood test to measure your 25(OH)D levels can tell you whether you have too high of vitamin D levels. If your 25(OH)D levels are above 150 ng/ml this is considered potentially toxic and potentially harmful to your health. You know if your 25(OH)D levels are toxic by a blood test to measure calcium. If calcium is high and 25(OH)D is high, then you are getting too much vitamin D.

Very high levels of 25(OH)D can develop if you:

    take more than 10,000 IU/day (but not equal to) everyday for 3 months or more. However, vitamin D toxicity is more likely to develop if you take 40,000 IU/day everyday for 3 months or more.
    take more than 300,000 IU in a 24 hour period.

If you have taken this much vitamin D, seek medical attention. Your health providers will get your calcium and 25(OH)D levels tested.

The current recommended daily allowances for vitamin D set by the Food and Nutrition Board are conservative, so you don’t need to feel worried about toxicity if you take more than their recommended daily allowance. You can find out more about daily vitamin D supplementation on our page, How do I get the vitamin D my body needs?
What should I do if I think I have taken too much vitamin D?

Have you taken more than 300,000 IU in the past 24 hours OR have you been taking more than 10,000 IU/day for the past three months or longer?

    If yes, check to see if you have symptoms of toxicity (listed above); symptoms like feeling sick, feeling thirsty, constipation or diarrhea, poor appetite and feeling confused. If so, you may have hypercalcemia and need medical attention.
        If you do not have any symptoms, you likely do not have hypercalcemia. However, you should get a blood test for 25(OH)D and make sure that you do not have a level above 150 ng/ml. Consider lowering your vitamin D dose. See our page How do I get the vitamin D my body needs? for more information.
    If no, you likely do not have hypercalcemia and are not toxic. If you are still concerned, you may choose to get a blood test to measure 25(OH)D to see what your levels are. See our Testing page for more information.
        If you have symptoms of toxicity but have not taken more than 300,000 IU in 24 hours or more than 10,000 IU/day for the past three months, you may have a very rare condition that is sensitive to vitamin D. Please see our Hypersensitivity page for more information.

What about children?

The more you weigh, the more vitamin D your body can handle; the less you weigh, the less vitamin D your body can handle. The above cutoffs of 300,000 IU in 24 hours or more than 10,000 IU/day for three or more months apply to average adult weight (125-200 lbs).

So, how do you know if your child has gotten too much vitamin D?

    For children that weigh 25 lbs or less, more than 50,000 IU in 24 hours or 2,000 IU/day for over three months is too much and potentially toxic.
    For children that weigh between 25 and 50 lbs, more than 100,000 IU in 24 hours or 4,000 IU/day for over three months is too much and potentially toxic.
    For children that weigh between 50 and 75 lbs, more than 150,000 IU in 24 hours or 6,000 IU/day for over three months is too much and potentially toxic.
    For children that weigh between 75 lbs and 100 lbs, more than 200,000 IU in 24 hours or 8,000 IU/day for over three months is too much and potentially toxic.

If your child has taken too much vitamin D, seek medical attention.
I already tested my 25(OH)D. Is my level too high?

If your level is greater than 150 ng/ml, this is considered too high and potentially toxic. Seek medical attention if you have symptoms of hypercalcemia (listed above). If you do not have symptoms, consider lowering your level. Please see our pages on 25(OH)D reference ranges and our page on how to get the right amount of vitamin D:

    Testing for vitamin D
    How do I get the vitamin D my body needs?

If your level is not greater than 150 ng/ml, then you are not potentially toxic in vitamin D. Please read our pages on vitamin D levels and how to interpret your results:

    I tested my vitamin D level. What do my results mean?
    How do I get the vitamin D my body needs?

References

    Cusano NE, Thys-Jacobs S and Bilezikian JP. “Hypercalcemia Due to Vitamin D Toxicity.” In Vitamin D, Third Edition, by Feldman D, Pike JW and Adams JS. Elsevier Academic Press, 2011.
    Vieth, R. Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety. American Journal of Nutrition, 1999.
 

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Re: 123 Days PF And I Think I know Why
Reply #2135 - Jan 24th, 2015 at 9:02pm
 
This is good its not too tecky and helps put the importance of Vit D into perspective,how it metabolises, its influence on DNA and also the bodies self limiting and self producing mechanisms. A truely remarkable substance that clearly has an impact on CH in some sufferers.
Unfortunately the science is not that well understood outside a few experts and then they are always learning.
One more post on synthetic non steroidal anti inflammatories which goes to emphasise that man can create all kind of drugs and not know how the hell they work


Vitamin D: a natural wonder drug we’re all avoiding?

Anna K Coussens

If you were told that there was one very cheap pill you could take every day that would help prevent cancer, diabetes, mental health problems, and multiple sclerosis while dramatically boosting your immune system, most of us would waste little time in popping out to the nearest pharmacy. In recent years, vitamin D has been shown to have a protective role in all of these diseases, yet at the same time the worldwide incidence of vitamin D deficiency is on the increase. You may have heard in the news that the incidence of rickets in children is on the increase, but did you realise that this is due to severe vitamin D deficiency and that a third of British children are thought to be vitamin D deficient? You may also remember the cases of ‘shaken baby syndrome’ where parents were accused of killing their children, but it turned out it was caused by weak bones due to vitamin D deficiency.

If you are unaware of the beneficial effects of vitamin D, you’re not the only one and it probably isn’t your fault as a recent study has shown that more than 50% of healthcare workers are also unaware of the benefits of vitamin D. In an attempt to combat this general lack of awareness clinicians and scientists have been pushing governments and advisory bodies to promote the benefits of vitamin D and increase their daily intake guidelines. In reply, the Chief Medical Officer for England, Dame Sally Davies, has recently advised that some groups, particularly pregnant women and the under-fives, should take a daily vitamin D supplement.

We all know that calcium is essential for bone growth, but fewer know that we need vitamin D for calcium adsorption. In fact, vitamin D is also essential for bone growth. However, vitamin D is not only essential for controlling calcium and phosphate levels, to maintain healthy bones. There is also growing scientific evidence that vitamin D is responsible for a whole host of other health benefits, including maintaining a healthy heart and brain, preventing cancer and diabetes and boosting your immune system.

One reason for its wide-ranging effects is that, unlike other vitamins, the major product of vitamin D, commonly called calcitriol, is actually a hormone. Whereas other vitamins, like vitamin C, need to be obtained from food and act as antioxidants or co-factors in enzymatic reactions, being a hormone means calcitriol is produced by specific cells to act as a messenger to tell other cells what to do. Calcitriol works by binding to the vitamin D receptor made by a certain cell, in the same way that a key fits its lock. Together they form a molecule which can help to turn on and turn off more than 900 genes in that cell. These genes control a diverse range of functions and it is therefore by acting as a key for this lock that the product of vitamin D, calcitriol, has an important role in maintaining a properly functioning body.
Figure 1.
Figure 1.

Click image to view at full-size

Vitamin D is obtained in two forms D2 (plant–derived) and D3 (UV/ animal-derived). Vitamin D is converted by cytochrome P450 (CYP) enzymes into calcidiol and calcitriol. Calcitriol controls the levels of CYP enzymes to make sure too much calcitriol isn’t produced. The blue line indicates inhibition, the red lines indicate activation.

It used to be thought that vitamin D was converted into calcitriol by two specific enzymatic reactions (Figure 1). The first step, occurring in the liver, produces calcidiol. This is the major form of vitamin D found in the blood and is what is measured to determine if someone is vitamin D deficient. The second step occurs in the kidney to convert calcidiol into calcitriol, through the action of the enzyme cytochrome 27B1 (CYP27B1). Low levels of calcium cause the parathyroid gland to increase production of the parathyroid hormone and this increases CYP27B1 production by the kidney, thereby increasing calcitriol levels. To make sure that too much calcitriol is not produced, calcitriol decreases parathyroid hormone production in order to limit CYP27B1 and its own synthesis.

In 1981, however, it was discovered that CYP27B1 and calcitriol could also be produced by a particular kind of immune cell, called macrophages. These cells act as the body’s rubbish collectors, ingesting and disposing of things the body doesn’t want, such as bacteria during an infection, debris from dying cells, or cancer cells. This was the first evidence that during an infection cells require high levels of calcitriol for optimum functionality. When macrophages sense bacteria they produce their own CYP27B1 so that they can make calcitriol, potentially at higher levels than they can get from the blood. This helps them turn on the genes they need to fight the infection. However, in order that the body doesn’t make too much calcitriol, calcitriol also activates the gene that makes another enzyme (called CYP24A1) which begins to degrade calcitriol. It is now known that many cell types will produce CYP27B1 in response to a range of stimuli. Consequently, vitamin D is now recognised to regulate numerous aspects of cell function, including cell growth, development, activation and death.
If it’s so good, how do we get it?

Vitamin D exists in two forms: vitamin D3 (cholecalciferol) and vitamin D2 (ergocalciferol) (Figure 1). Vitamin D3 is the predominant form in humans and is primarily obtained through skin exposure to UV irradiation from the sun. This converts a substance in the skin (which comes from lanolin) into vitamin D3. It is generally thought that between 5–30 minutes of midday sun exposure (10am-3pm) at least twice a week to the face, arms, legs, or back, without sunscreen, is required to maintain sufficient levels of vitamin D. You get the same amount of vitamin D whether you have 30 minutes exposure or 8 hours, as the heat generated in the skin by the UV will degrade any excess vitamin D produced. A very specific wavelength of UV (UVB) is required for vitamin D production. How close to the equator you live, the season, time of day, cloud cover and smog can all affect the wavelength you are exposed to. Skin colour (determined by the amount of the pigment melanin in your skin) and sunscreen use can also affect the amount of UV radiation that your skin cells receive. Therefore, if you have darker skin you need longer exposure to the sun in order to make the same about of vitamin D3 as someone who has pale skin. Vitamin D3 can also be obtained from dietary sources such as oily fish and eggs and their derived products like cod liver oil. Vitamin D2 is obtained from plant sources, primarily fungus and yeast exposed to UV irradiation, or from nutritional supplements (see historical note).

Where you live is one of the major factors that influences how much vitamin D you get. Equatorial countries, which are sunnier, have a greater steady state of vitamin D than countries at northern or southern latitudes, where seasonal variation in daylight hours is greatest. Even within the UK, if you live in Scotland you are three times more likely to be vitamin D deficient than someone in the southeast of England, as Scotland has a lot less daylight throughout the year (Figure 2). There is growing evidence for associations between geographical vitamin D levels and neurological conditions such as multiple sclerosis (MS), depression and brain development. There is an association between the season during which a pregnant woman has her third trimester and the neurological development of her baby, summer being optimal to maximise vitamin D levels. The severity of MS symptoms can also vary by season.

Older adults are particularly at risk of developing vitamin D deficiency because as they age, their skin cannot synthesize as much vitamin D. Other populations at risk include those who cover their entire body in clothing, indoor dwellers, night workers and people with inadequate intake of vitamin D rich foods, particularly fatty fish. This latter point is of particular note for expectant mothers who are advised to avoid certain seafoods during pregnancy, but total seafood avoidance will increase their risk of vitamin D deficiency. Furthermore, as vitamin D is a fat soluble molecule, calcidiol is stored in fat and its release into circulation is altered by excess stores of body fat. Consequently, obesity is another risk factor for vitamin D deficiency.
Figure 2.
Figure 2.

Click image to view at full-size

UK average annual sunlight duration per day varies according to latitude and corresponds to the gradient of vitamin D deficiency throughout the country.

The ability to tan has been shown to be inversely proportional to vitamin D synthesis. This is because the skin pigment (melanin) blocks UV from penetrating deep within the skin. Many researchers now worry that excessive use of sunscreen, which was encouraged to prevent UV-induced DNA damage and skin cancer, is leading to an epidemic of vitamin D deficiency - particularly in a country like the UK, where UV exposure is moderate in comparison to Australia where the recommendations for sunscreen originated. In support of this idea, reports are emerging from sunny countries that the risk of a second primary cancer after having a non-melanoma skin cancer (the less aggressive form) is lower for nearly all cancers investigated. This is because non-melanoma skin cancers reflect cumulative sun exposure, whereas melanoma (the most aggressive form) is more related to sunburn. Consequently, extended sun exposure, without burning has been shown to prevent melanoma.
How does vitamin D affect so many functions of the body?

We now know that outside the kidney, calcitriol can be made by a range of other cell types including lung, skin, colon, pancreatic, brain, breast and various immune cells (Figure 3). For a cell to respond to calcitriol it needs to make a vitamin D receptor. However, to be an active receptor the vitamin D receptor must also bind to the vitamin A receptor. Binding of calcitriol to these two receptors forms an active molecule called a transcription factor which can bind to a gene’s specific DNA sequence and cause it to be turned on. By controlling the activation of genes, calcitriol affects a wide range of processes within a cell. However, vitamin D metabolites are not the sole activators of the two receptors. Retinoic acid (a form of vitamin A) in combination with calcitriol has been shown to regulate genes in macrophages which help them to kill intracellular bacteria and inhibit their ability to ingest bacteria. This suggests that maintaining physiological levels of both vitamin D and vitamin A may be important for correct functioning of the receptor complex.

The main function of vitamin D is to maintain healthy bones by controlling blood calcium levels. However, calcium is also required for muscle function and deficiency can lead to low muscle strength, again which can be associated with falls and secondary fractures. Conversely, excess calcitriol causes high calcium levels, which can lead to kidney stones, kidney failure and cardiac failure. Luckily this can be prevented if detected early enough.

One of the ways calcitriol helps the body’s immune system to fight infection is by turning on genes which make small proteins called antimicrobial peptides, particularly one called cathelicidin. This small protein has been shown to kill many different pathogens, including bacteria such as M. tuberculosis, Staphylococcus aureus and E. coli, fungi such as Candida albicansand viruses such as herpes simplex virus type 1, influenza and human immunodeficiency virus type 1 (HIV-1). The mechanisms of killing are not completely understood, but it is known that cathelicidin kills bacteria by punching holes in their cell wall. So far we know that cells in the skin, lung, eye, colon, as well as many immune cells all make cathelicidin when sufficient vitamin D is available.
Figure 3.
Figure 3.

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Calcitriol, the active form of vitamin D, affects the function of many organs in the body.

Paradoxically, despite its ability to induce antimicrobial activity, calcitriol also inhibits many pro-inflammatory signalling molecules (called cytokines and chemokines) which activate and recruit other immune cells and induce anti-inflammatory signals from various immune cells. In general, immune cells make pro-inflammatory cytokines to help activate the immune response during an infection. Recruiting and activating other cells at the site of disease results in the inflammation and raised temperature we all associate with being sick. In many chronic infections, however, excess inflammation can lead to tissue damage. It is believed that calcitriol limits the inflammatory immune response to prevent excess tissue damage at the same time as having direct antimicrobial activity to kill the invading pathogen.

It is via its anti-inflammatory effects that vitamin D is also thought to help in various autoimmune diseases which develop due to inappropriate chronic inflammation, including type 1 diabetes, inflammatory bowel disease (ulcerative colitis and Crohn’s disease), rheumatoid arthritis and asthma. Excess inflammation is also thought to be a damaging factor in neurological conditions where the degree of inflammation is proportional to the severity of symptoms, as occurs in MS. Vitamin D has been shown to reduce inflammation caused by repeated trauma to peripheral nerves in chronic regional pain syndrome and reduce the risk of vascular dementia. However, this link to dementia may also be due to the beneficial effects of vitamin D on the cardiovascular system. As vitamin D limits inflammation and tissue destruction, it also has a positive effect on preventing the thickening of arterial walls which is the main cause of cardiovascular disease and stroke. Vitamin D deficiency is associated with increased blood pressure and severely deficient newborns can have heart failure.

Another way vitamin D can limit tissue damage is by controlling the expression of matrix metalloproteinases (MMPs): enzymes which are capable of degrading all components of the tissue within which cells live. MMPs are generally produced by cells to help repair damaged tissue. Long term MMP activity can cause tissue destruction in chronic inflammatory conditions, such as tuberculosis TB, psoriasis, eczema and asthma, while it also allows cellular migration in metastatic cancers. In work carried out at NIMR, it has been shown that the levels of various MMPs are increased in the blood of tuberculosis (TB) patients and that supplementation with vitamin D during anti-TB therapy significantly reduces the levels of MMPs along with many other pro-inflammatory signals. This is interpreted as good evidence that vitamin D helps to resolve the pathological inflammation which destroys the lung during TB. Lung destruction is what causes TB patients to cough up blood, an image forever linked with the consumption epidemics of the 17th and 19th centuries.

While vitamin D can play a role in limiting cancer metastasis through limiting tissue destruction, it may also control cancer by stopping cell growth, as has been shown for breast cancer cells. However, the majority of evidence for a role of vitamin D in cancer comes from studies showing that vitamin D deficiency and low sun exposure are associated with increased risk of cancer incidence and mortality. Cancers linked to vitamin D deficiency include breast, colon, ovarian, pancreatic, prostate, oesophageal, gall bladder, gastric, rectal, renal and vulvar cancer, melanoma and Hodgkin’s and non-Hodgkin’s lymphoma. In the UK, prostate cancer risk is inversely proportional to the extent of UV exposure, skin colour and sunbathing on holiday. Contrary to links between UV exposure and cancer, childhood sunburn was found to be protective against prostate cancer in UK males. There are also many studies which show no correlation between UV exposure and cancer. The difficulty in finding conclusive evidence for the role of vitamin D in cancer is complicated by the multiple environmental and genetic factors involved (including diet, geographical location, skin colour and genetic predisposition) and the length of time over which cancer develops.

Vitamin D also plays a vital role in maternal health during pregnancy and lactation, particularly during the second and third trimesters. Children born in spring have been shown to have the highest rates of mental disorders (such as depression and schizophrenia) and autoimmune diseases (such as type 1 diabetes and asthma) and expectant mothers are at highest risk of vitamin D deficiency during this time. Higher doses of vitamin D supplementation during pregnancy have been shown to reduce infections and the risk of preeclampsia in mothers, and to increase the bone and muscle strength of their children. Vitamin D deficiency is also associated with the severity of polycystic ovary syndrome symptoms and fertility rates can be enhanced by vitamin D supplementation.
How much vitamin D do we really need?

So if that’s what we currently know about the benefits of vitamin D and the risks of vitamin D deficiency, are we giving people the right advice about vitamin D intake? Because circulating calcidiol levels may not always be indicative of what is occurring within a cell, determining adequate vitamin D levels based solely on blood calcidiol is difficult. The level you choose to define 'deficiency' will depend on what physiological process you are trying to maintain. An individual’s requirement will also depend on how well they can actually metabolise vitamin D, transport it to where it is required and how active their vitamin D receptor is. All of these factors can vary between individuals due to their genetic variation. The highest levels of vitamin D are required to maintain optimal functionality of all processes which vitamin D is thought to be involved in. Lower levels will only maintain the vital roles of vitamin D in controlling calcium and bone health.

Determining recommended daily intakes (RDI) also depends on an individual’s sun exposure, sun screen use, ability to tan and skin colour. Therefore, determining an RDI that suits everyone is difficult. The fact that sunlight can provide a huge burst in vitamin D levels suggests that supplementation can be carried out at higher levels than currently recommended and still remain safe. There is more evidence pointing to the health benefits from higher concentrations of vitamin D than to deleterious effects. Two internationally recognised bodies have recently published revised supplementation guidelines. A panel of clinicians from the USA Institute of Medicine (IOM) published one report, and a group of scientists and clinicians from the Endocrine Society published a reply to that report. The conclusions of the two studies are conflicting, with regard to RDI for optimal health outcome. The first is cautionary, underplaying the evidence, the second is realistic in recommending levels not greater than can be obtained naturally from the sun. The major difference was the definition of vitamin D deficiency categorised by the two studies: the IOM specified 20 mg/L as the level based predominantly on benefits to bone health, while the second study categorised people between 20-30 mg/L as being insufficient and more than 30 mg/L as sufficient. However, the later study also suggested that 40-50 mg/L will promote optimal health benefits, with regard to non-bone related functions.While you may not understand what these numbers represent, the fact that the second study recommended double the amount of vitamin D for optimal health, highlights the present conservatism of some advisory bodies. The IOM set their RDI at 600 units per day, while the Endocrine Society paper recommended at least 600 units per day to prevent deficiency and 1500-2000 units per day for optimal health. Higher levels were also recommended for the elderly and obese people in both studies. The upper limit set by the two studies was 4,000 units per day and 10,000 units per day, respectively.

So why was the IOM so cautious in their recommendations? What’s bad about too much vitamin D? Historically, dangerously high levels were prescribed, inducing extremely high levels of calcium which in some cases resulted in kidney failure and cardiac failure. This made clinicians cautious in overprescribing supplements. However, these original studies used extraordinarily high doses, hundreds of times higher than the upper levels which are in dispute by these two studies. Moreover, no toxic effects have been associated with levels of 10,000 units/day, even in patients with an illness. Moreover, when an adult wearing a bathing suit is exposed to the amount of UV which will result in a slight pinkness in the skin, the amount of vitamin D produced is equivalent to ingesting between 10,000 and 25,000 units.

I am Australian and I love the sun. However, being of British heritage means I am blessed with pale, sunburn-prone skin and as such I am cautious when it comes to sun exposure. Despite this, I spent my first summer after moving to London making sure I got out in the sun on the weekends as much as possible, while ensuring I did not get sunburnt. Towards the end of summer, I had my vitamin D measured and was happily surprised to find I had a calcidiol level of 43.6 mg/L - the optimal level recommended by the Endocrine Society. Thus even in an English summer, with only intermittent sun exposure I had reached a level more than double what the IOM has now classified as sufficient. So, if you can naturally make more than 40 mg/L in an English summer, is this level really bad for you? With growing evidence suggesting there are multiple beneficial effects of having calcidiol levels more than 40 mg/L and few negative effects, perhaps we should encourage higher levels in order to promote greater health benefits and a preventative health care policy, rather than recommending levels at the bottom end of healthy, based predominantly on one physiological system (i.e. maintaining healthy bones)? I, for one, trust nature to deliver what I need. If regular sun exposure can give me 43.6 mg/L in summer, then I will take supplements to give me that level when I have limited sun exposure in winter. I wait in anticipation for the revised NICE guidelines for vitamin D. I hope you look out for them too!
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Re: 123 Days PF And I Think I know Why
Reply #2136 - Jan 24th, 2015 at 9:10pm
 
Sorry if these are long but the devil is unfortunately in the detail, this post if fleshed out could make the basis for a phd thesis by detailing the molecular makeup, the dna interactions, the receptor thingies, the efficacy for original purpose and the spread of application the drugs have now and of course cost and the social impact availability vs prevalence of complaints (treatable by said drugs) in economically challenged populations / regions

from emedexpert.com (for purpose of review only)

Non-Steroidal Anti-Inflammatory Drugs Comparison

    Uses
    Types
    Mechanism of action
    Differences between NSAIDs
    Side effects
    Contraindications
    Cost
    Conclusions

Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most commonly prescribed medications worldwide. They relieve pain and inflammation in many disorders.

Nonsteroidal anti-inflammatory drugs have anti-inflammatory, analgesic, and antipyretic effects and inhibit thrombocyte aggregation. NSAIDs are used primarily to treat inflammation, mild-to-moderate pain, and fever. NSAIDs also are included in many cold and allergy preparations.

NSAIDs block the Cox enzymes and reduce prostaglandins throughout the body. As a consequence, ongoing inflammation, pain, and fever are reduced. Since the prostaglandins that protect the stomach and support the platelets and blood clotting also are reduced, NSAIDs can cause ulcers in the stomach and promote bleeding.

Uses

NSAIDs are usually indicated for the treatment of acute or chronic conditions where pain and inflammation are present. Nonsteroidal anti-inflammatory drugs are powerful analgesics, especially for nociceptive pain. NSAIDs also are effective in some neuropathic pain syndromes when used with other analgesics.

NSAIDs are indicated for the symptomatic treatment of the following conditions:

    Rheumatoid arthritis. NSAIDs are particularly useful in the inflammatory forms of arthritis (such as rheumatoid arthritis) and, sometimes, in the more severe forms of osteoarthritis.
    Osteoarthritis
    Acute gout
    Inflammatory arthropathies: ankylosing spondylitis, psoriatic arthritis, Reiter's syndrome
    Dysmenorrhoea (painful menstruation), menstrual cramps
    Headache and migraine
    Postoperative pain
    Mild-to-moderate pain due to inflammation and tissue injury
    Back pain and sciatica
    Sports injuries, sprains, and strains
    Dental pain
    Pain from kidney stones (renal colic)
    Reduction of fever
    Prevention of blood clotting (Aspirin only)

Note: NSAIDs do not cure the diseases or injuries.

Types of NSAIDs

There are many different types of NSAIDs, which are categorized according to their chemical structures:

Salicylates:

    aspirin (Ascriptin, Bayer, Ecotrin)
    diflunisal (Dolobid, Diflunisal)
    salsalate (Argesic SA, Disalcid, Salflex, Salsitab, Mono Gesic)

Arylalkanoic acids:

    diclofenac sodium (Voltaren)
    diclofenac potassium (Cataflam)
    indomethacin (Indocin)
    etodolac (Lodine)
    sulindac (Clinoril)
    tolmetin (Tolectin)

Pyrroles:

    ketorolac (Toradol)

Arylpropionic acids (profens):

    ibuprofen (Motrin, Advil)
    ketoprofen (Orudis, Oruvail)
    dexketoprofen ()
    naproxen (Naprosyn, Alleve)
    fenoprofen (Nalfon)
    flurbiprofen (Ansaid)
    oxaprozin (Daypro)

Enolic acids (oxicams):

    piroxicam (Feldene)
    meloxicam (Mobic)
    lornoxicam
    tenoxicam (Mobiflex)

Fenamates:

    mefenamic acid (Ponstel)
    meclofenamate (Meclomen)
    niflumic acid
    tolfenamic acid
    flufenamic acid

Pyrazolones:

    metamizole (dipyrone)
    phenazone (antipyrine)
    aminopyrine (aminophenazone)
    propyphenazone
    phenylbutazone

Sulphonanilides:

    nimesulide

Napthylalkanones:

    nabumetone (Relafen)

COX-2 Inhibitors:

    celecoxib (Celebrex)
    etoricoxib (Arcoxia)
    parecoxib (Dynastat)

Acetaminophen, ibuprofen, naproxen, and ketoprofen are available over-the-counter in the United States.

Mechanism of action

NSAIDs work by suppressing the production of prostaglandins. Prostaglandins are chemical messengers that mediate inflammation, fever and the sensation of pain. NSAIDs block the production of prostaglandins by inhibiting the action of an enzyme, cyclooxygenase (COX). This enzyme is responsible for converting precursor acids into prostaglandins.

Prostaglandins formed via COX-1 activity control renal perfusion, promote platelet aggregation and provide gastroprotection by regulating mucous secretion. Prostaglandins formed via COX-2 activity mediate pain, inflammation, fever and inhibit platelet aggregation.

In the periphery NSAIDs work by decreasing the sensitivity of the nociceptor to painful stimuli induced by heat, trauma, or inflammation. In the central nervous system, they are thought to function as antihyperalgesics and block the increased transmission of repetitive incoming signals to higher centers. In effect, they modulate perception of pain caused by repetitive stimulation from the periphery. Since they function by modulation of the perception of pain, they may be useful when given in the preoperative period and may reduce the need for postoperative analgesia.

The anti-inflammatory activity of NSADs in descending order:
indomethacin > diclofenac > piroxicam > ketoprofen > lornoxicam > ibuprofen > ketorolac > acetylsalicylic acid

NSAIDs that inhibit both COX-1 and COX-2 enzymes are named non-selective NSAIDs. NSAIDs that mainly inhibit COX-2 enzymes are named COX-2 inhibitors (Coxibs).

Classification of NSADs by selectivity to cyclooxygenase (according to “Drugs Therapy Perspectives”, 2000):
Pronounced selectivity towards COX-1      Aspirin
Indomethacin
Ketoprofen
Piroxicam
Sulindac
Moderate selectivity towards COX-1      Diclofenac
Ibuprofen
Naproxen
Equal inhibition of COX-1 and COX-2      Etodolac
Meloxicam
Nimesulide
Nabumetone
Pronounced selectivity towards COX-2      Celecoxib

Differences between NSAIDs

The principal differences among NSAIDs lie in the time to onset and duration of action. Also, these drugs vary in their potency and how they are eliminated from the body.

Another important difference is their ability to cause ulcers and promote bleeding. The more an NSAID blocks COX-1, the greater is its tendency to cause ulcers and promote bleeding.

Aspirin is a unique NSAID but because it is the only NSAID that is able to inhibit the clotting of blood for a prolonged period (4 to 7 days). This prolonged effect of aspirin makes it an ideal drug for preventing the blood clots that cause heart attacks and strokes. Most other NSAIDs inhibit the clotting of blood for only a few hours.

Bromfenac was recently approved by the FDA for the treatment of postoperative inflammation and reduction of ocular pain in patients who have undergone cataract extraction. Earlier bromfenac was removed from the market because of reports liver damage associated with its use.

Celecoxib has a sulfonamide structure and is contraindicated for patients with known sulfa allergy.

Dexketoprofen is available as the tromethamine salt -- dexketoprofen trometamol. Dexketoprofen is the S(+) enantiomer of the racemic compound ketoprofen. Clinical studies showed that dexketoprofen has good analgesic and safety profiles, comparable to those of other NSAIDs7.

Diclofenac is relatively long acting (6 to 8 hours) but it has a relatively very short half-life. Diclofenac is also a unique member of the NSAIDs. There is some evidence that diclofenac inhibits the lipoxygenase pathways, thus reducing formation of the leukotrienes (also pro-inflammatory autacoids). There is also speculation that diclofenac may inhibit phospholipase A2. These additional actions may explain the high potency of diclofenac - it is one the most potent NSAIDs.

As an analgesic, diclofenac is 6 times more potent than indomethacin and 40 times as potent as aspirin in the phenyl benzoquinone-induced writhing assay in mice.

Diclofenac use increases the risk of heart attack and stroke.

Etodolac, with regard to its anti-inflammatoryproperties, is approximately 50 times more active than aspirin, three times more potent than sulindac, and one-third as active as indomethacin. Although etodolac is no more potent than many other NSAIDs, a low incidence of GI side effects is an important therapeutic advantage.

Fenoprofen has less potent in anti-inflammatory action than ibuprofen, indomethacin, ketoprofen, or naproxen.

Flurbiprofen was found to be 536-fold more potent than aspirin and 100-fold more potent than phenylbutazone. Oral flurbiprofen is half as potent as methylprednisolone. Flurbiprofen is 26 times more potent than ibuprofen as an antinociceptive.

Ibuprofen has the lowest risk of causing GI bleeding.

Indomethacin, a very potent COX inhibitor, besides its high cardiovascular risk, has a significant GI toxicity and many central nervous system side effects. Indomethacin should not be used by children <14 years and during pregnancy.

Indomethacin is still one of the most potent NSAIDs in use. It is also a more potent antipyretic than either aspirin or acetaminophen, and it has about 10 times the analgesic potency of aspirin. However, its beneficial analgesic effect is definitely overshadowed by pronounced side effects.

Ketoprofen, unlike many NSAIDs, inhibits the synthesis of leukotrienes and leukocyte migration into inflamed joints in addition to inhibiting the biosynthesis of prostaglandins. Ketoprofen stabilizes the lysosomal membrane during inflammation, resulting in decreased tissue destruction. Although it is less potent than indomethacin, its gastrotoxicity is about the same. Ketoprofen may cause photosensitivity.

Ketorolac is the most potent and most effective NSAID analgesic, with efficacy comparable to opioids4. The analgesic effect of 30 mg of ketorolac is similar to 10 mg of morphine. Anti-inflammatory activity is achieved only at doses higher than those needed for analgesia. Ketorolac has the highest incidence of side effects, and is, therefore, not used for more than five days.

Lornoxicam is unique among the enolic acid derivatives in that it has a rapid onset of action and a relatively short half-life (3 to 5 hours).

Meloxicam was initially introduced as a selective COX-2 inhibitor. However, it is less selective for COX-2 than is celecoxib. Meloxicam causes fewer GI complications than piroxicam.

Metamizol is a potent and promptly acting analgesic and antipyretic. Its anti-inflammatory activity is poor. Metamizol was banned in the USA and some European countries due to several reported cases of agranulocytosis. It has been extensively used in India and other European countries. Moreover adverse effects data collected over 4 decades shows that risk of toxicity with metamizol is lower than with aspirin.

Nabumetone represents a new class of nonacidic prodrugs. Nabumetone offers distinct advantages over other NSAIDs with regard to low incidence of GI side effects, ulcers and bleeds. Based on available data, nabumetone does not appear to be associated with increased cardiovascular risk5. Nabumetone may cause photosensitivity.

Naproxen provides effective relief in acute traumatic injury and for acute pain associated with migraine, tension headache, postoperative pain, postpartum pain, pain consequent to various gynecologic procedures, and the pain of dysmenorrhea. Naproxen has a lowest risk of provoking heart attack. It may cause photosensitivity.

Oxaprozin has a rapid onset of action and a prolonged duration of action (half-life ranges from 26 to 92 hours). It is mainly used as an anti-inflammatory agent. It also has uricosuric properties and is used in the treatment of gout. Oxaprozin may cause rash and mild photosensitivity.

Piroxicam has a long plasma half-life (38 hours), which permits a single daily dosing. Piroxicam is indicated for long-term use in rheumatoid arthritis and osteoarthritis. Its gastrotoxicity is relatively high.

Sulindac, an analog of indomethacin, is unique among the NSAIDs in not inhibiting prostaglandin synthesis in the kidneys 6. So, it may be one of the safest drugs for treating osteoarthrosis in older people. Sulindac may cause increased liver enzymes.
Comparative efficacy: which NSAID is the best?

It is a common misconception that all NSAIDs are therapeutically equally efficacious and any one of them could be used for the given condition. For example, ankylosing spondylitis responds better to a particular NSAID like indomethacin. It is probably related to its stronger inhibition of prostaglandin synthesis.

Oxaprozin, aspirin, ibuprofen, indomethacin, naproxen, and sulindac have comparable efficacy in the treatment of rheumatoid arthritis.

Oxaprozin, aspirin, naproxen, and piroxicam have comparable efficacy in osteoarthritis.

The analgesic effect of 10 anti-inflammatory drugs was compared using a single-blind method in 90 patients with rheumatoid arthritis. Each patient received two different drugs, for three days each and each drug was evaluated in 18 patients. After the trial, the patients considered which of the drugs they preferred. The greatest relief from pain was achieved by diclofenac, indomethacin, naproxen and tolfenamic acid, each of these being preferred by the majority of patients and being significantly better than the least effective drugs ketoprofen and proquazone. Acetylsalicylic acid, azapropazone, carprofen and ibuprofen were considered intermediate in efficacy.

Side Effects

NSAIDs are associated with a number of side effects. The two main adverse reactions, associated with NSAIDs relate to gastrointestinal effects and renal effects. These effects are dose-dependent, and in many cases severe enough to pose the risk of ulcer perforation, upper gastrointestinal bleeding, and death, limiting the use of NSAID therapy.

Cardiovascular side effects

Diclofenac has a cardiovascular risk very similar to rofecoxib, which was withdrawn from worldwide markets owing to cardiovascular toxicity2.
Naproxen does not appear to increase cardiovascular risk suggesting that it is the safest NSAID with respect to cardiovascular toxicity.

NSAIDs rated by relative risk for cardiovascular events (in ascending order) 2:

Naproxen < Celecoxib < Piroxicam < Ibuprofen < Meloxicam < Indomethacin < Diclofenac < Rofecoxib (at doses more than 25 mg)

Gastrointestinal adverse effects

The main of NSAIDs is that they can cause ulcers and other problems in the esophagus, stomach, or small intestine. Common gastrointestinal side effects include: nausea, vomiting, dyspepsia, peptic ulcers, perforations of the upper gastrointestinal tract, and gastrointestinal bleeding.

Relative risks of gastrointestinal complications 3:

    Low Risk: ibuprofen, aceclofenac, nimesulide, fenoprofen, aspirin, diclofenac, sulindac, nabumetone etodolac
    Medium Risk: diflunisal, naproxen, indomethacin, tolmetin, meloxicam
    High Risk: piroxicam, ketoprofen, azapropazone, flurbiprofen, ketorolac

Risk of ulceration increases with duration of therapy, and with higher doses. In attempting to minimize gastrointestinal side effects, it is prudent to use the lowest effective dose for the shortest period of time. To help protect the stomach, NSAIDs should always be taken with food or directly after a meal.

Hypertension (High blood pressure)

NSAIDs have potentially adverse effects on blood pressure. All NSAID users experience some degree of salt and water retention, and hypertension occurs in less than 10% of users.

NSAIDs-induced hypertension is due to the renal effects of these drugs. Specifically, NSAIDs cause dose-related increases in sodium and water retention. In addition, NSAID use may reduce the effect of antihypertensive drugs except calcium channel blockers.

Kidney damage (nephrotoxicity)

NSAIDs reduce the blood flow to the kidneys, which makes them work more slowly. This is due to the inhibition of production of the vasodilatory renal prostaglandins. When the kidneys are not working well, fluid builds up in the body leading to edema. The more fluid in the bloodstream -- the higher blood pressure. The reduced blood flow can permanently damage the kidneys. It can eventually lead to kidney failure and require dialysis.

Renal impairment is especially a risk if a patient concomitantly takes an ACE inhibitor, a diuretic, or other nephrotoxic agent.

NSAIDs are cleared from the blood stream by the kidney, so it is very important that patients over 65 years of age or patients with kidney disease consult a physician prior to taking them. If patients take an NSAID for an extended period of time (six months or more), a blood test needs to be performed to check for early signs of kidney damage.

Most people with chronic kidney disease are advised to avoid all types of NSAIDs.

Allergic reactions

NSAIDs can also cause extreme allergy. People with asthma are at a higher risk for experiencing serious allergic reaction. Many specialists recommend that people who have asthma stay away from any NSAID, especially if they have sinus problems or nasal polyps. Individuals with a serious allergy to one NSAID are likely to experience a similar reaction to a different NSAID.

Use of aspirin in children and teenagers with chicken pox or influenza has been associated with the development of Reyes's syndrome. Therefore, aspirin and nonaspirin salicylates (e.g. salsalate) should not be used in children and teenagers with suspected or confirmed chicken pox or influenza.

NSAIDs do not cause bleeding, but they make bleeding worse, for example, when there is a cut.

A meta-analysis of 11 case-control studies and one cohort study found that ibuprofen was significantly less toxic than other NSAID.

Serious side effects are especially likely with one nonsteroidal anti-inflammatory drug, phenylbutazone. Patients of age 40 and over are especially at risk of side effects from phenylbutazone, and the likelihood of serious side effects increases with age. Because of these potential problems, it is especially important to check with a physician before taking this medicine. Never take it for anything other than the condition for which it was prescribed, and never share it with another person.

Contraindications

NSAIDs cannot be used (are contraindicated) in the following cases:

    Allergy to aspirin or any NSAID
    Aspirin should not be used under the age of 16 years
    During pregnancy
    During breast feeding
    On blood thinning agents (anticoagulants)
    Suffering from a defect of the blood clotting system (coagulation)
    Active peptic ulcer

Cost

Numerous NSAIDs are available as generics and include: diclofenac, etodolac, fenoprofen, flurbiprofen, ibuprofen, indomethacin, ketoprofen, meclofenamate, naproxen, piroxicam, sulindac, and tolmetin. Only meloxicam (Mobic), nabumetone (Relafen), and oxaprozin (Daypro) are available by brand name only. Generics may be an equally effective and less expensive option.

Conclusions

All NSAIDs are similarly effective. The choice of which NSAID to try first is usually empiric. If one doesn't provide adequate pain control, try switching to another. All NSAIDs when used chronically can contribute to the development of ulcers. Differences in adverse effects seem to exist between different NSAIDs. Follow with your doctor closely and watch for signs or symptoms of gastrointestinal bleeding such as stomach pain and blood in the stools. Some NSAIDs are available in extended-release formulations that require less frequent dosing.
References & Resources

    1. The Merck Manual of Medical Information. Mark H. Beers et al., eds. 2nd Home Edition. Whitehouse Station, NJ: Merck; 2003.
    2. McGettigan P, Henry D. Use of non-steroidal anti-inflammatory drugs that elevate cardiovascular risk. PLoS Med. 2013;10(2):e1001388.
    3. Castellsague J, Pisa F, Rosolen V, Drigo D, Riera-Guardia N, Giangreco M, Clagnan E, Tosolini F, Zanier L, Barbone F, Perez-Gutthann S. Risk of upper gastrointestinal complications in a cohort of users of nimesulide and other nonsteroidal anti-inflammatory drugs. Pharmacoepidemiol Drug Saf. 2013 Apr;22(4):365-75.
    4. Gora-Harper ML, Record KE, Darkow T, Tibbs PA. Opioid analgesics versus ketorolac in spine and joint procedures: impact on healthcare resources. Ann Pharmacother. 2001 Nov;35(11):1320-6.
    5. Bannwarth B. Safety of the nonselective NSAID nabumetone : focus on gastrointestinal tolerability. Drug Saf. 2008;31(6):485-503.
    6. Dunn MJ, Patrono C, Cinotti GA: Prostaglandins and the Kidney: Biochemistry, Physiology and Clinical Applications. New York, Plenum Publishing Corp., 1983.
    7. Zippel H, Wagenitz A. A multicentre, randomised, double-blind study comparing the efficacy and tolerability of intramuscular dexketoprofen versus diclofenac in the symptomatic treatment of acute low back pain. Clin Drug Investig. 2007;27(8):533-43. PubMed

Published: May 05, 2007
Last updated: August 07, 2014
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Re: 123 Days PF And I Think I know Why
Reply #2137 - Jan 24th, 2015 at 10:44pm
 
All too much to absorb, but yes, their are no drugs as of
yet to treat CH's, they are all cross over drugs, that's what
makes it so hard to find drug to suit a particular individual
that works for him/her. We clusterheads are all different.

Hoppy.

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Re: 123 Days PF And I Think I know Why
Reply #2138 - Jan 25th, 2015 at 1:50am
 
Thanks Hoppy,

Lancashire Lad was obviously on a roll posting two large data dumps on vitamin D3 and one on NSAIDs.

I've only a couple of comments.  The first responds to "Is vitamin D3 safe?"

You bet it is !!! And with the exception of oxygen therapy which is also very safe CH abortive, vitamin D3 it's far safer and more healthy as a CH preventative than any of the standards of care preventative medications typically prescribed for CH.

I know safety of nutrients like vitamin D3 can be a concern for some so here are a few factoids... 

In the history of the FDA's adverse reaction database that's been running for 11 years, there hasn't been a single death attributed to vitamin D3.  In the four year's I've been posting about this regimen at CH.com with over 600 CH'ers taking this regimen, there hasn't been a single report of an adverse reaction or vitamin D3 intoxication.

Can you take too much vitamin D3? Yes... but get real, at the sustained doses discussed in this thread, vitamin D3 is very safe...  Drinking too much water can be fatal.

If you want a real scare, click on the following link. It will open up to Naproxen, (Aleve).

Multimedia File Viewing and Clickable Links are available for Registered Members only!!  You need to Login or Register

When it comes up, be sure to click on the "show more" hot link under the first set of bar graphs then scroll down to see the number of deaths...  Then enter vitamin D3 and do the same...

After that, enter any of the over-the-counter medications in your kitchen or bathroom cabinet in the search window.  When you're done with the OTCs enter any of the Rx meds you've had prescribed to treat your CH.

Lancashire Lad, if you want to do some real heavy reading before your next post, try GrassrootsHealth and Mercola... Both sites have a wealth of information about vitamin D3. 

If you want to see the mother load of information on vitamin D3, go to Vitamin D Wiki.  Henry Lahore is the prime mover behind this website.  He has multiple web crawlers running 7 X 24 picking up all things vitamin D including hundreds of results from RCTs involving vitamin D3 as the primary method of intervention.  You can spend weeks reading through this website.

Henry also provides an assessment and commentary on most of the RCTs.  He correctly points out when the dose of vitamin D3 is too low, when there are no vitamin D3 cofactors included, and when it appears there's an obvious bias in the conclusions...  In other words, Henry is always very objective in his analysis of articles and studies on vitamin D3.

This is a practice all of us should follow.

Remember, Big Pharma doesn't want people to know how effective vitamin D3 at therapeutic doses (costing 12 cents a day) can be in preventing and treating a wide range of medical conditions...  What was the actual cost of that last injection of sumatriptan succinate (Imitrex)? 

Take care,

V/R, Batch
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« Last Edit: Jan 25th, 2015 at 1:53am by Batch »  

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Re: 123 Days PF And I Think I know Why
Reply #2139 - Jan 25th, 2015 at 3:54am
 
Yes Hoppy too much I agree, and Batch my intention was to draw attention to the fact that by and large we are all victims of a "suck it and see" approach to alleviating the the worst of the worst headaches.

I wasn't having a pop at  your Vit D therapeutic regime, why should I, it works for some?

You mention the safeness of oxygen, you better than most know the toxic and deleterious effects of oxygen at raised and reduced pressure, there are also issues that can be met with over therapeutic use of oxygen at normal atmospheric pressure (note ozone is incredibility lethal, but that is obviously a different molecule to the one we are talking about.

Oxygen is an even more complex subject than Vit D when it comes to interaction with humans.

What I think is important (and it isn't to everyone) is trying to understand the pharmacological effects of natural and synthetic drugs on head pain and their secondary influences on the rest of the body.

I don't medicate well at all, propranalol, at normal doses it knocks me for six as do other Beta and other inhibitors. Yes it can be said its safe but not for me I'm afraid (I'm not talking about causing discomfort propranalol at an accepted normal dose nearly killed me once.

People die from eating nuts and being stung by bees, we are not all the same and do not react the same to so called safe substances. Most people tolerate cannabis some it sends daft. One mans "safe" is another man's poison.

Its not possible to understand all the interactions and  outcomes of drug use for extreme (even moderate) headaches, the subject is too complex which often leaves the experts stumped.

So we have to rely on statistics and empiric data to reach individual solutions And this is, I suppose where I coming from. It has ever been thus. Our forefathers learned which herbs and botanical substances treated various ailments along with the early mushroom pickers; if it didn't kill them and created a desired outcome then try it again and if it works suggest it to someone else and if they die exercise caution in recommending it to anyone else.

Progress is never made by accepting perceived wisdom. To push forward the alleviation of head pain its only by testing, experimenting, analysing and studying that true progress is made. They're still needlessly pulling teeth out in the UK to relieve head pain but occasionally it works that doesn't mean we should all go and have our teeth pulled out. But if I was told by an expert that there was a good chance that I would never have the ultimate headache ever again, I'm not sure I would go along with it but I am confident some would.

"Pharmacology" is derived from the words for the study of poison in classic Greek, in modern Greek it means study of drugs.
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« Last Edit: Jan 25th, 2015 at 4:16am by lancashire Lad »  
 
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Re: 123 Days PF And I Think I know Why
Reply #2140 - Jan 25th, 2015 at 7:05am
 
Hi Thierry,
I was on Zomig some years ago, but can't say it worked. It's so long ago now I can't remember the dose, but I'm due back with the Doc in two weeks, so I'll talk to him about it.
I use gammaCore which works up to a 7/8 or if you get it early.
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Expensive, but if the D3 works, well, I won't need to use it very often, or ever, please God.
Keep well,
Peter.
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Re: 123 Days PF And I Think I know Why
Reply #2141 - Jan 25th, 2015 at 5:47pm
 
G'day Lancashire lad, and Batch,
I noticed in your post the part about vitamin D that you
are an Aussie now living in the UK, and grabbing as much
sun as possible during the summer months, not an easy
thing to do at the best of times, being an ex pat myself
now living in the land down under lol, but all jokes aside,
I remember going to my GP a few years ago now, long
before my wife found this website bless her cotton socks
for my annual check up, and when my results came back
he said my vitamin D level was on the low side, and to
pop into the pharmacy on my way home to get some
vitamin D3 tablets, so even being exposed to the sun
wearing shorts and a tea shirt most days of the year
I still wasn't getting enough vitamin D to sustain a healthy
bone structure, but thanks to the vitamin D regime I now
have strong bones, and no CH's.

Cheers, Hoppy.


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Re: 123 Days PF And I Think I know Why
Reply #2142 - Jan 25th, 2015 at 9:03pm
 
G'day Hoppy

I have been politely asked to sod off this thread because I have been deemed not very helpful. It's a sentiment that I can relate to and funnily enough one that I found refreshing from this forum. I had started to fear that I had wandered into a Stepford Wives world of headachers where everyone is calm, measured and polite if a little down in the dumps at times.

Me, I'm as angry as hell at the way the whole professional medical community has managed the problem of extreme headaches (there are obviously some great docs out there but many of them are pissing in the wind).

My background is in science and I was often called on to come up with explanations why things had failed (below water, above water, on land and at extreme pressure) but my approach was always that of an engineer rather than a scientist even if my reports read as scientific papers.

I owe you a debt Hoppy, you were kind enough to give me some pointers, I researched my particular problem and found a solutions that appears to be working for me. (whoopi me!)

But I have become v interested in the entire field of extreme headaches and have used my research style to map out markers of common experiences, diagnoses and outcomes. The work is at a very rudimentary level but some interesting interactions are appearing in a multidimensional matrix.

One very simplified (at the moment) area of interest that is flagging is the interactions of Vit D, Calcium, Calciium, Blockers (particularly Verapamil at this rudimentary stage) Blood Pressure, BP Meds., oxygen, Antagonist (eg Kinin), Atmospheric pressure and pressure changes and lifestyle / physical atributes of sufferers vs remission cases and a tiny few identical twin cases. This is not at DNA analysis level except where it cannot be ignored, and other stuff.

I like to work backward from the cause not forward from a serendipitously sent "solution".

I have no gripe with anyone who finds relief from a particular regime and has no interest in how it works, it just does and they are grateful as hell.

Me I like to know how and why things work.

As you are aware there in a ton of research out there, and a  myriad of personal experiences to make use of; the scale of  the task of making sense of the problem is immense

Its not acceptable for someone to suffer for 5 years or longer before their very real extreme misery is tackled by the medical profession even if the solution is gained through trial and error of various remedies. I live in the UK so that invariably means the lucky patient is trialled with the cheapest offering first and then moved up the economic burden scale until a satisfactory regime is identified.

As mentioned I'm butting out, not in a fit of pique but because I don't feel I have anything to offer this group I will send you my email, I would like to keep in touch with you but I don't envisage me coming up with any groundbreaking announcements in the near future. But I was able to identify my problem (with your help) get an MRI and explain to the doc what I thought the problem was quit all my meds; max daily dose of paracetamol, asprin, ibuprofen, codiene 120mg Tramadol 100mg, Amitryptoline 40mg and caffein 720mg. And get the drug that I guessed would work, it did, now I am virtually pain free and playing with the dosage of a single drug Indomethacin. After more than a year of constant headaches and daily v extreme and getiing worse, I think that was a result to achieve all that in less than 3 weeks.

No I'm not Mr Wonderful but when I put my mind to something I generally get results.

Cheers Hoppy and Good Luck to all other members, Luck is an important ingredient to gaining relief from this monster. 
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Re: 123 Days PF And I Think I know Why
Reply #2143 - Jan 25th, 2015 at 11:33pm
 
G'day Lancashire Lad,
Thanq for your kind words, and was pleased to read things
are working out for you now. Wishing you lots of PFD my
friend.

I find it strange that you are getting some flak from this
thread, nobody is putting a gun to there head that they
have to read it, I must say I found it very interesting after
spending a couple of days absorbing it all lol, and Batch's
input was very enlightening.

Cheers, Hoppy.




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Re: 123 Days PF And I Think I know Why
Reply #2144 - Feb 1st, 2015 at 4:12am
 
Hi,

I am a so called ICCH.  In other words, an Intractable chronic cluster head.

I do not respond to most of the standards of care meds / treatments recommended for CH.
At one point, out of desparation, I underwent a surgical procedure to implant electronic stimulators on my geater occipital nerves (GON) in the back of my head.  Although promising with some relief during the day, the GON stimulation ultimately faild to control my CH at night.  In retrospec, implantation of the GON stimulators was a very expensive gambit that didn't work.

What I can say now with a high degee of certainty is – I've tried all the stadards of care CH preventatives and abortives.  I've also tried experimental medical treatments, and even some of the alternative therapies.  At best, the results were mixed. Few of these treatments proved effective with any measure of lasting relief and most resulted in adverse reactions that made their continued use unacceptable. 

The two treatments that did work were oxygen therapy at flow rates that support hyperventilation as my CH abortive and the ANTI INFLAMMATORY REGIMEN TREATMENT (AIRT) as my CH preventative.

The primary goal that I as well as my doctors are working towards is:

Provide relive from pain, and provide (me) with the possibility of living a very normal life!

The ANTI INFLAMMATORY REGIMEN TREATMENT  (AIRT) allows me to meet that goal and more !

I have been under very close medical supervision and monitoring with frequent lab tests to check for the possible adverse effects while taking the AIRT.  My Neurologist, my Endocrinologist and my Pain specialist (Anaesthesiologist) team up to view the results of each exam and lab test to help me achieve this goal.
All of them seemed to be very apprehensive about this treatment in the beginning.  Now, after more than a year observing me and all my lab results
very closely, they are happy with the significant reduction in pain symptoms and the complete absense of any adverse effects associated with this regimen. The AIRT is not a cure for CH, but it does provide me with the exciting possibility of an exceptionally good quality of life.  In short, as long as I continue to take this regimen, I no longer suffer from the debilitating effects of CH!  Moreover, there are no adverse side effects !  I might add that the side effects I have experienced are all beneficial...  I feel better, sleep better, I have fewer colds and I have more strength.  I'm likely healthier now than before my CH started.

Another reward of taking this regimen is I enjoy all these benefits at a fraction of the cost of all the standards of care meds I used to take!

Everyone is happy  –  I'm Happy, my Medical insurance company is happy and so are my doctors. The hospital is also happy as I've become one less patient to “clutter” the "over cluttered” waiting room.

Michael
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Re: 123 Days PF And I Think I know Why
Reply #2145 - Feb 1st, 2015 at 1:41pm
 
I've now gone past the 3 years CH pain free milestone thanks to D3, so another success story for what this can do.
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Re: 123 Days PF And I Think I know Why
Reply #2146 - Feb 2nd, 2015 at 10:23pm
 
Hey Michael,

Your post says it all...  I'm thinking there are likely a few CH'ers still considering neurostimulation implants to control their CH... 

I hope they take your experience as a lesson learned that doesn't need to be repeated...

Take care and thanks for the great post.

V/R, Batch
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Re: 123 Days PF And I Think I know Why
Reply #2147 - Feb 3rd, 2015 at 7:17pm
 
Hi Batch and all the rest,

After nearly a month on the Anti-Inflammatory Regimen I can report fantastic results, five days in my CH were clearly diminishing and now I’m pain free for over two weeks!!!

This is even better than the day I found oxygen. Smiley

I had to slightly modify the regimen because I have “Gastroparesis” and can not tolerate fish oil. However I can tolerate krill oil, this is the only significant change I have made.

I had my blood tested a few day after I started to check my 25(OH)D unfortunately my neurologist requested the wrong tests.  Sad

PFDAN

Rick
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Re: 123 Days PF And I Think I know Why
Reply #2148 - Feb 4th, 2015 at 12:07am
 
Hey Reek,

Great news.  Thanks for the feedback on your experience with this regimen.  It's a great feeling isn't it?

Take care and please keep us posted.

V/R, Batch
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You love lots of things if you live around them. But there isn't any woman and there isn't any horse, that’s as lovely as a great airplane. If it's a beautiful fighter, your heart will be ever there
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Re: 123 Days PF And I Think I know Why
Reply #2149 - Feb 5th, 2015 at 2:53pm
 
Hey Batch,

I recently started a cycle after being pain-free for over 8 months on this regimen.

Got hit with multiple KIP 5-6 last night.

Currently I'm taking (with dinner):

Fish Oil - Kirkland 2 x 1200 mg (w/ 684 mg of Omega-3)
Magnesium Citrate - Vitamin Shoppe 2 x 200 mg
Centrum Silver
Zinc Oxide - Nature Made 15 mg
K2 - Life Extension Super K
Vitamin C - 4 x 1000 mg (one with dinner, the other 3 throughout the day)

D3 - Nature's Bounty 15,000 IU dissolved in mouth before bedtime

Melatonin - Natrol 10 mg slow release before bedtime

I also added B-50 Complex back into my regimen a few days ago.  The last time I took B-50 for 90 days was from 4/18/14-7/17/14. 

I'm going to start drinking a baking soda tonic 3 times/day to possibly get my arterial pH up a little.

I have an appointment to test my 25(OH)D levels next week.

Anything else you would recommend?  Is it ok that I started the 90-day B-50 dose again?
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