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Migraine is complex.

At least migraine seems complex – because we don’t know what causes it.

But we’re making progress. There is an emerging consensus about what’s important in migraine – and what’s not important. So in this brief summary we’ll stick to what most experts think are the important parts.

Though migraine is complex – we’ll keep it simple – adding only those details required for a basic understanding – keeping in mind that the goal is getting better, not just getting smarter.

Migraine is simple.

At the most basic level, having migraine means having a sensitive neurovascular system. I don’t have migraine (my wife does) but if my brain was sufficiently ’stressed’ (challenged by things it does not like), a migraine attack would eventually ensue – it’s just that quite a bit of stress would be required to make that happen. The level of stress required to trigger an attack is what defines migraine disease – and the severity of migraine disease.

Migraine is triggered by nerve signals that cause the release of inflammation causing substances. Odd as it might seem, nerve impulses release these inflammation causing substances all the time – in everyone – in moderation. Migraine means that something’s not quite right. It might be that too many nerve signals are being generated – or too much of the ’substance’ is being released – or that there is an excessive reaction to that substance – or some other thing/combination that results in excess sensitivity.

The inflammation that’s caused by nerve activity is called neurogenic inflammation. In the case of migraine, it’s the blood vessels of the brain that become inflamed – and probably the nerve itself . We’ll look at that nerve in a moment. It’s a big one – the trigeminal – with a central portion located in the brainstem and numerous branches – some of which go to the face – others of which go to the blood vessels of the brain.

Once nerve signals trigger the initial inflammation of the brain’s blood vessels, that inflammation irritates and inflames other, nearby nerves. That causes those nerves (which are very close by) to send return signals that ’something is wrong’ (e.g. pain signals.) Unfortunately, those signals only make things worse, because they cause more inflammation back at the site where the first signal originated.

That original site (sometimes called the “migraine generator”) ends up being more ‘excited’ (and inflamed) than it was to begin with – so it starts sending even more inflammation-causing signals back up to the blood vessels of the brain. It’s a vicious cycle – one that ultimately leads to a full-blown migraine attack.

The most likely structure responsible for initiating and perpetuating that vicious cycle of neurogenic inflammation is the trigeminal nerve and its associated structures.

Without going into detail, the trigeminal nerve is a very large nerve – actually more like a big bundle of nerves. The trigeminal nerve ‘bundle’ has branches that go to the face. It also has branches that go to the blood vessels of the brain.

The various ‘bundles’ of the trigeminal nerve come together in the brainstem in a big clump. Different parts of the big clump can be referred to as a “ganglion” or a “nucleus”. It’s all part of one big interconnected nerve bundle, so we’ll just refer to all of it as the trigeminal or, sometimes, the “trigemino-vascular” system (to emphasize the fact that it connects with, affects, and is affected by the blood vessels in the brain.)

When the trigeminal becomes inflamed, that inflammation can affect other parts of the brainstem, which could explain the nausea, vomiting and certain other symptoms common to migraine. Plus, there’s some ‘inter-mingling’ of trigeminal nerve fibers with those of the seventh cranial nerve, which might explain why migraine can cause symptoms like tearing, bloodshot eyes and stuffy nose – because stimulation of the seventh cranial nerve can have those effects.

So there’s a number of reasons to believe that the “migraine generator” is in the brainstem – and that it might be the trigeminal itself.

In fact that’s one point on which there is emerging consensus – that the trigeminal is critical in migraine. To keep things simple, we’ll assume that migraine starts in the trigeminal and is perpetuated by the trigemino-vascular system.

Likewise, it’s pretty well accepted that inflammation plays a critical role in migraine – specifically neurogenic inflammation. What’s less certain are which chemical mediators of inflammation are most important in the neurogenic inflammation process. Molecules considered possibly important include calcitonin gene-related peptide (CGRP), nitric oxide (NO), substance P, glutamate, tumor necrosis factor (TNF), neurokinin A, serotonin – and quite a few others. Of those listed above, there is emerging consensus on the importance of at least two: CGRP and NO.

CGRP is known to be released, in excess, by the trigeminal during migraine. CGRP is associated with pain and inflammation. Migraine is relieved when CGRP receptors are blocked, and a new class of anti-migraine drugs is being developed which do just that – block CGRP receptors. In clinical trials, the CGRP receptor blockers have shown about the same effectiveness in treating migraine as triptans, but they may have fewer side effects. Speaking of triptans, at least part of their effectiveness may result from their ability to inhibit the release of CGRP. So there are many reasons to believe that CGRP is important in migraine.

NO is also known to be present, in excess, in association with migraine. Nitroglycerin (NTG) administration (generates NO in the body) causes a migraine headache, especially in those with migraine disease. NO stimulates the release of pro-inflammatory agents from the trigeminal, especially CGRP. In fact, the presence of excess NO might be required for CGRP release. Plus, NO is generated in the blood vessels of the brain in response to the excess serotonin released during a migraine attack. Finally, blocking NO has been shown to be effective in the treatment of migraine. So there are many reasons to believe that NO is important in migraine.

Here’s where it seems science is at – the present consensus on what’s important in migraine:

• Neurogenic inflammation is important.

• The trigeminal – or trigemino-vascular system – is important.

• CGRP is important.

• NO is important.

So going forward those things are about all we’ll talk about. Except that we’ll also talk about NF-kB, because NF-kB is the inflammation Master Switch, and because everything that’s important in migraine might relate back to NF-kB.

Migraine is a disease of inflammation.

According to the theory advanced on this site (in brief) every ‘disease of inflammation’:

1. Is caused by inflammation…
2. that results from over-activation of NF-kB…
3. that can be treated by administering NF-kB inhibitors – especially natural (plant derived) NF-kB inhibitors.

That’s a very simple theory. It might be wrong. It’s definitely incomplete. But at least it’s actionable.

If it’s right – or to the extent it’s right – then we can treat migraine by using a combination of natural NF-kB inhibitors. That might be quite advantageous because – in addition to helping a lot of people – such a product would be:

• Relatively inexpensive.

• Relatively free from side effects – and perhaps entirely free from serious side effects.

The brief outline that follows is a little more complicated than it might be (sorry) – but I want to stay consistent with the expert consensus on what’s important.

Evidence for each of the following – if found – would support (but not prove) the theory in regard to migraine:

• Migraine is associated with inflammation, and more specifically:
  • Migraine is associated with inflammation in the trigeminal, and/or;
  • Migraine is associated with inflammation of the blood vessels of the brain.

• Migraine is associated with excess NF-kB activation, and more specifically:
  • Migraine is associated with excess NF-kB activation in the trigeminal, and/or;
  • Migraine is associated with excess NF-kB activation in the blood vessels of the brain.

• Migraine is associated with a defect (especially genetic) or vulnerability that results in excess activation of NF-kB.

• Inhibiting NF-kB is beneficial in the treatment of migraine, and more specifically:
  • Inhibiting NF-kB in the trigeminal is beneficial, and/or;
  • Inhibiting NF-kB in the blood vessels of the brain is beneficial.

• Natural NF-kB inhibitors are beneficial in treating or preventing migraine, especially:
  • If they specifically act in the trigeminal, and/or;
  • If they specifically act in the blood vessels of the brain.

Hopefully that makes sense. Now we’ll go through the outline and check for evidence in support of each statement. Note that “true” means only that there is evidence in support of that contention.

Migraine is associated with inflammation – true.

• There is extensive evidence for the central role of inflammation in migraine.
• Inflammation in pediatric migraine is documented. Increased levels of IL-1 and TNF – both mediators of inflammation – have been documented.
• Inflammation results from cortical spreading depression (CST) – CST is associated with the aura in those who have aura. The inflammation resulting from CST was documented by a PET scan.

• Migraine is specifically associated with inflammation in the trigeminal – also true.
  • Increased levels of inflammatory mediators such as TNF, CGRP are seen in the trigeminal in association with migraine.
  • Neuronal inflammation in the trigeminal has been documented in migraine.
  • Inflammation of the trigemino-vascular system is documented. Inflammatory changes observed include mast cell degranulation, plasma protein extravasation and other changes characteristic of ‘typical’ inflammation.
• Migraine is specifically associated with inflammation of the blood vessels of the brain – seems to be true.
  • Migraine is consistently characterized by edematous, dialted cranial vasculature, presumably resulting from, or at least consistent with, cerebro-vascular inflammation.
  • The migraine induced inflammation of the trigemino-vascular system extends to the vessels of the brain.
  • Markers of inflammation are elevated in the blood during migraine.

Given all the above, it’s clear that migraine is a disease of inflammation. Next…

Migraine is associated with excess NF-kB activation – true.

• Elevated NF-kB is among the markers of inflammation found in the blood during an acute migraine attack.
• NF-kB is upregulated prior to the surge in iNOS (generates NO) expression associated with migraine.

• Migraine is specifically associated with NF-kB activation in the trigeminal – also true.
  • Nitroglycerin administration precipitates a migraine attack in vulnerable individuals – that attack is preceded by an increase in the level of activated NF-kB in the trigeminal.
  • Increased Inflammation has been shown to result in upregulation of trigeminal NMDA receptors essential for pain transmission in migraine – the upregulation in NMDA receptors is secondary to NF-kB activation in the trigeminal.
  • High levels of TNF, CGRP and activated NF-kB in the trigeminal characterize the acute migraine attack.

• Migraine is specifically associated with NF-kB activation in the blood vessels of the brain – also true.
  • During an acute migraine attack, blood drawn from the internal jugular vein showed excess activation of NF-kB. The authors even suggest that NF-kB inhibitors might be used in the successful treatment of migraine.

So it appears migraine is associated with a lot of NF-kB activation, both in the trigeminal and in the blood vessels of the brain.

Migraine is associated with a defect (especially genetic) or vulnerability that results in excess activation of NF-kB – no evidence.

• Migraine is clearly linked to genetic inheritance, but the basis for that linkage remains elusive – we can’t find the genes.
  
• Not what we’re looking for, but perhaps of interest: migraine is associated with a lack of responsiveness by vascular smooth muscle to NO. The researchers who investigated seemed to be looking for a way to explain the higher cardiovascular risk in migraine – and found that the vessels were not very responsive to NO – they had trouble dilating (getting bigger.) This is the opposite of what I would have guessed. I would have guessed that they became enlarged (as in migraine) very easily. Hmmm…
  • Could it be that migraine results (genetically) from some dysfunction in NO processing by the blood vessels?
  • Might the result of diminished vascular response to NO be some compensatory overproduction of NO – which might then lead to inflammation of the trigeminal?
    

Inhibiting NF-kB is beneficial in the treatment of migraine – true.

• A number of medications that prevent migraine inhibit NF-kB. I find this very interesting – most of the medications that prevent migraine also inhibit NF-kB. (Then why don’t they do a better job of preventing migraine? Probably because they are only weak inhibitors of NF-kB.)
• A possible triptan analog inhibits NF-kB – triptans might act, in part, through inhibition of NF-kB. This one is really quite a stretch – I looked long and hard for a study that investigated the effect of triptans on NF-kB and could not find one – this is the closest I could come – and it’s not all that close.
• NO is of central importance in migraine, and NF-kB inhibition has been shown to decrease NO.
• CGRP is of central importance in migraine, and NF-kB inhibition has been shown to inhibit CGRP release.
• A number of observations support NF-kB as a molecular target in migraine therapy.

• Specifically inhibiting NF-kB in the trigeminal is beneficial in the treatment of migraine – also true.
  • NF-kB inhibition in the trigeminal inhibits the upregulation of NMDA receptors there.
  • Nitroglycerin (NTG) can trigger a migraine. Parthenolide was shown to reduce the severity of the migraine resulting from NTG administration by blocking NF-kB activation in the trigeminal.

• Specifically inhibiting NF-kB in the blood vessels of the brain is beneficial in the treatment of migraine – no evidence. (But the finding of elevated NF-kB in the internal jugular, combined with the fact that NF-kB controls inflammation, and that inflammation of the vessels plays a role in migraine, strongly suggests this would be true.)

So far, so good – it looks like migraine is a disease of inflammation – that is associated with NF-kB activation – and that inhibiting NF-kB is helpful. Two publications go so far as to say that NF-kB would be a good target for a migraine drug. I agree. Let’s continue.

Natural NF-kB inhibitors are beneficial in treating or preventing migraine – true.

• Administration of feverfew and ginger, both natural inhibitors of NF-kB, was shown to be effective in the treatment of migraine.
• Aspirin – which is a natural product slightly altered – and which acts in part via inhibition of NF-kB, is at least somewhat effective in the treatment of migraine.
• Ginger – a natural NF-kB inhibitor – has been found effective at reducing platelet aggregation, suggesting it might be effective in the treatment of migraine.
• Parthenolide, the active ingredient in feverfew and a natural NF-kB inhibitor, was found to be effective as an inhibitor of NO, though apparently by some mechanism other than inhibition of NF-kB.
• An extract of feverfew, which is a natural NF-kB inhibitor, has been shown effective in the prevention of migraine.
• Traditional Chinese medications for migraine have been found to be inhibitors of NF-kB.

• Natural NF-kB inhibitors that specifically inhibit NF-kB in the trigeminal have been shown beneficial in migraine – true.
  • Feverfew has been shown to inhibit NF-kB in the trigeminal, resulting in decreased production of NO and a reduction in migraine following NTG administration to susceptible individuals.

• Natural NF-kB inhibitors have specifically been shown beneficial in migraine through the inhibition of NF-kB in the blood vessels of the brain – no evidence.

There is evidence that natural NF-kB inhibitors are effective in the treatment of migraine – specifically that parthenolide, the purported active ingredient in feverfew, is effective – and that it works by inhibiting NF-kB in the trigeminal.

One problem with feverfew is that it does not seem to be all that effective. A comprehensive review of feverfew use for the prevention of migraine concluded that feverfew might work – or it might not. There just wasn’t enough evidence (but the review did conclude that feverfew was safe.) Even if we look at the trial where feverfew seemed to perform best, it just wasn’t all that effective. The active product decreased the monthly number of migraine attacks from 4.8 to 2.9, a decrease of 1.9, but the placebo reduced attacks by 1.3 each month. And it took 2-3 months before the effect of feverfew extract kicked in.

Another problem is that we only have evidence for feverfew/parthenolide. There are many other natural NF-kB inhibitors – but it seems their use in the treatment of migraine has not been investigated.

One reason for that – the lack of investigation – is that once a molecule looks interesting, and has been shown to do something, it’s going to be further investigated. So if you go to the PubMed database and search for “parthenolide” you’ll find (as of 12-18-09) 353 citations (and 18 citations for parthenolide + migraine.) Search curcumin (an NF-kB inhibitor and the active ingredient in turmeric) and you’ll find 3,112 results – but zero results for curcumin + migraine. That’s because curcumin, unlike feverfew, has no history of use in migraine.

Which means curcumin does not work for treating migraine. At least not by itself. We would know if curcumin worked for migraine because millions of people use curcumin. If it worked, someone would have figured it out by now (”Hey, ever since I started taking curcumin I don’t get migraine headaches!”)

That doesn’t mean curcumin can’t act with other NF-kB inhibitors to enhance their efficacy.

We’ll get to that in a moment. But for now let’s forget about feverfew, or any specific plant, and instead focus on the principle. Natural NF-kB inhibitors may be effective. We have evidence for one. We have ignorance regarding many. We know that we need more effect than what feverfew alone can deliver.

But let’s keep going. This is fun, right?

CGRP vs. NO – which is more important?

Both calcitonin gene-related peptide (CGRP) and nitric oxide (NO) appear to play a critical role in the initiation and progression of a migraine attack – but is one more important than the other? If so, which one? (And does it matter?)

One way to view ‘importance’ is to look at which factor is dependent on, or ‘downstream’, from the other. Generally speaking we’re much better off targeting the ‘upstream’ factor – at least so far as efficacy is concerned.

NO controls CGRP – so NO is more important, and a better target for therapeutic intervention.

That appears to be the case, because:

• CGRP has no effect in the absence of NO.
  • When rats were given CGRP – they didn’t seem to mind at all.
  • When those rats were given NTG their cells generated a lot of CGRP – and they were soon in obvious pain.
• NO synthase inhibitors reduce the effects of CGRP – suggesting that CGRP production, release, and activity are dependent on NO.
• The fact that NO plays a key role in all headache suggests its primacy.

NO is upstream from CGRP – so it’s a better target than CGRP – but what’s upstream from NO?

NF-kB controls NO (and CGRP) – so NF-kB is more important, and a better target for therapeutic intervention.

• Nitric oxide production is under the control of NF-kB at every step.
• NF-kB inhibition blocks NO production.
• NF-kB inhibition also blocks CGRP production and release (as expected, since CGRP is downstream from NF-kB.)

Both NO and CGRP are important – and both are controlled by NF-kB.

Here’s the stream: NF-kB => NO => CGRP

First choice for an effective migraine medication would be to inhibit excess NF-kB, second choice would be to inhibit NO, third choice to inhibit CGRP.

Both triptans and CGRP receptor blockers work at the CGRP level, which is probably why their efficacy in migraine is ‘only’ about 60% at 2 hours.

Inhibiting excess NF-kB activation might produce far better results. And if we could inhibit NF-kB, then it wouldn’t really matter (to answer an earlier question) whether CGRP or NO is more important – since they are both downstream from, and under the control of, NF-kB.

NF-kB is the ultimate target in migraine because it’s not only the inflammation Master Switch – it’s also the migraine Master Switch.

So we really need to find a way to affect NF-kB – because we really want to get rid of migraine.

Returning to the principle – we have shown that a natural NF-kB inhibitor ’should’ work – or at least that it could work. We have one example of a natural NF-kB inhibitor that (probably) does work – feverfew and its active ingredient parthenolide. But we need more than what feverfew alone can deliver.

By expanding on what we know, it might be possible to achieve the desired effect.

The first step is to combine multiple NF-kB inhibitors. Specific natural NF-kB inhibitors have been selected, based on a rational process, with the intent of creating the most effective product while using the least possible amount of each individual extract. Each individual extract has a several thousand year history of safe use. None of the extracts would be effective (at all) if used alone.

The second step, equally important, is to deliver the extracts in such a way as to ensure maximum bio-availability. Specifically, by formulating the combination of natural NF-kB inhibitors as a lozenge, so that they can be absorbed through the mucous membranes of the mouth. That way the important molecules (whatever they might be) reach the bloodstream – and the brain (trigeminal) – without first being exposed to the very harsh environs of the stomach.

You may be familiar with the process by which natural plant extracts are separated from cellulose enclosures and presented to the mucosal membrane of the mouth for direct absorption into the bloodstream. It’s called “eating”. Assuming you chew your food, whenever you eat fruits and vegetables you’re absorbing natural NF-kB inhibitors through the mucous membranes in your mouth. There’s nothing odd or dangerous about it. What’s odd is that no one seems to think it’s important.

The end result – a combination of plant extracts in the form of a lozenge – is Banjo.

In theory it should work – and it does. No one to date has had a migraine while using Banjo – and the people who have used Banjo have had some pretty nasty migraine disease.

I’m sure I’ll need to change the above paragraph soon – and I’m not sure it should be included even now. I’m leaving it because it’s a way of letting people know what to expect. Banjo isn’t the sort of thing you use in hopes that your migraine attacks might decrease by 20% in three months. Banjo is supposed to make your migraine attacks stop – right away – entirely. That’s the goal.

Banjo can be used as an acute treatment for migraines. It works when used that way – but like all migraine medications, it works much better if taken early in the course of an attack.

The ideal use of Banjo is in the prevention of migraine attacks. There are about 2.5 million people in the US who experience acute migraine one or more days a week. Those are the people I would really like to see using Banjo – the people whose lives are most impacted by migraine – the ones for whom, it seems, nothing else works.If you know anyone like that, please send them here. I’ll be happy to send them whatever they need. For now at least, everything is free – nothing is for sale. (That will change at some point – sorry.)

One last note

The historical use of feverfew goes back thousands of years – but had somehow fallen out of favor until, sometime around 1950, a woman in England rediscovered feverfew for the prevention of migraine.

Of course she couldn’t go to the store and buy it. She simply found some feverfew and chewed on the leaves – which is probably how most herbal remedies were administered in the past. In any case, by chewing on the leaves she found that, over time, her migraines went away – or at least diminished in number.

Her discovery was eventually published in a local magazine. Word spread and soon hundreds, then thousands of people all across England began chewing on feverfew leaves. It must have worked – at least a little – because feverfew became quite popular. So popular in fact that ‘nutrition’ companies started making and selling a feverfew product. What did they sell? Well, dried up bits of feverfew leaf packed inside a gelatin capsule, of course.

Feverfew remains popular to this day, and you can buy it (the dried up bits of leaf inside a gelatin capsule) in any health food store. But you can’t buy the leaves. My guess is that those capsules don’t work so well. They might not work at all. I don’t know.

But I would guess that the woman who first rediscovered the usefulness of feverfew could set us straight. I imagine her saying “I told you to chew the leaves – chewing the leaves is what works!”

And I would add – on what basis have you come to believe that chewing a fresh leaf is the same as swallowing whole a ground up, dessicated product wrapped in gelatin?

Yes, chewing the leaf might be somewhat unpleasant and inconvenient. Then again, migraine disease tends to be rather unpleasant and inconvenient.

If you want to use feverfew for migraine, then I suggest you either purchase fresh leaf (I have no idea where) or grow your own. Why not? It’s an attractive plant that grows almost anywhere. I have some in my perennial garden (in Minnesota.) It resembles a daisy.

In the alternative you can use Banjo. It tastes better than feverfew leaf (in my opinion) and it’s quite a bit more effective.

Turmeric (curcumin) shown to improve multiple sclerosis, rheumatoid arthritis, psoriasis, and inflammatory bowel disease

Let’s take a look at a recent publication that briefly reviews curcumin for autoimmune disease.

We’ll see that curcumin (an active ingredient in turmeric,) is recognized as safe, and that it has recently been shown to be effective against several serious conditions in human and/or animal studies.

That sounds promising. But your doctor will never have a chance to prescribe it for you – and will probably never tell you about it. Why might that be?

Let’s start by taking a look at the abstract.

The history and likely future of curcumin (turmeric)

The list of disease conditions associated with “a breakdown” of the immune system is sobering. That these very serious, often debilitating and sometimes life threatening conditions collectively effect 5% of the world population should emphasize the urgency with which this problem must be addressed.

The author next observes that dietary supplement use is on the rise. Hardly surprising given the assessment that they are “effective, inexpensive, and relatively safe.”

Next comes a list the conditions for which curcumin (a component of turmeric) seems to be effective, followed by a brief explanation of how curcumin generally affects the immune system – by regulating inflammation.

Given all this, we must be well on our way to a new, effective treatment for these devastating conditions. Very exciting.

But no. Using higher doses for therapeutic treatment requires “extreme caution.” (Not just caution, mind you – “extreme” caution.) We can’t do anything, it seems, until we first have a precise understanding of the effective dose, safe regiment, and mechanism of action. (Not just an understanding – a “precise” understanding.)

I don’t want to seem as if I’m picking on this author. I’m not. I very much appreciate the review.

And I don’t disagree regarding the need for caution, especially when one component of a plant (in this case curcumin) is given in concentrated form. I think the full-spectrum extract of turmeric (e.g. as used in Banjo) is a better, more effective, safer alternative. And I happen to believe “higher doses” of curcumin are not required. But if you want concentrated curcumin you can purchase it in any health food store. Thousands do every day, and no significant side effects have been reported – ever. In fact a recent trial showed that up to 8 grams (8,000 mg) of pure curcumin taken daily for 4 months was safe.

What I object to is that natural products are viewed with such suspicion. Rather than expressing excitement over what might be an effective treatment for conditions that currently devastate the lives of millions – and for which there are few if any good treatments – only “extreme caution” is recommended. Yes, let’s be cautious – always. But let’s also recognize that curcumin has been in a real world ‘clinical trial’ for thousands of years and that it has performed well. Let’s not throw up artificial, unrealistic barriers to its use, such as the need to “precisely understand” its mechanism of action.

Here are the number of prescription pharmaceuticals for which we “precisely understand” the mechanism of action: 0.

OK, there might be a few where our understanding could be called “precise” – but there are far more where the mechanism of action is entirely unknown. The FDA does not need to know the precise (or any) mechanism of action before approving a new drug. A new drug need only be shown “safe and effective.”

Curcumin (turmeric) has a long history of safe use and is reported by thousands (millions?) to be effective. Additionally, as the author notes, a number of recent studies in animals and humans have shown it to be effective.

Given all this, it seems not much additional work should be required to determine the best dose at which curcumin can be safely and effectively used – either for autoimmune disease or the other numerous conditions it helps with.

Not much work, relatively speaking – but there is a problem. No one is doing that work.

So it’s not just that you’ll have to wait a long time for your prescription for curcumin. It will never arrive.

That might be (should be) very distressing to you. But it should not lead you to believe what is not true. No, the drug companies do not want to keep you sick. No, there is not a conspiracy among doctors to hide the cure for cancer, or warts, or any other condition. Your doctor genuinely wants you to get well and the pharmaceutical companies genuinely want to offer new, effective drugs. Yes, the pharmaceutical company wants and needs profit – just like your doctor – just like me – just like you.

And that is the problem – or a large part of the problem. There is no economic model that supports development of prescription curcumin. The clinical trials required to satisfy the FDA would cost at least (I’m guessing) $30 million? $50 million? Far more, actually, because in addition to out of pocket expenses the FDA process would require substantial time and effort on the part of many pharmaceutical employees. Other projects would have to be deferred. And since curcumin cannot be patented, their investment would amount to a donation. Anyone could sell it. Walgreen’s would have it on the end cap in all their stores. Sales at GNC would be going gangbusters.

Given that curcumin might be the greatest new drug in the last 50 years, maybe you think some generous pharmaceutical company ’should’ make this donation – just for the good of the world. But you cannot believe they are malicious for not doing so.  That just wouldn’t be fair.

So while it’s probably true that no pharmaceutical company is working on curcumin, it’s also true that many are probably working with curcumin – trying to alter it so it becomes patentable. Maybe they can do that without diminishing its efficacy – and without creating a product that has serious side effects. Or maybe they can’t.

I guess we’ll just have to wait and see.

While we’re waiting, there’s turmeric (or curcumin.)  Use it as you see fit – but realize you’re on your own.

Very few doctors are well-informed on turmeric (or any natural product) and fewer still will advocate using anything not approved by the FDA. You will not see television commercials for turmeric. Your insurance company will not pay for it.

You’re on your own. Is this a good thing? No, but it is what it is. You and I can rail against the system, or we can spend our efforts looking for what works – trying to get better.

Should you be cautious, educate yourself and act prudently? Of course. As much or more with this issue as with any other. And yes, there is some dangerous stuff out there. And yes, people do foolish things.

But don’t let anyone tell you that it’s wrong, or dangerous, or foolish to look for what works. Don’t let anyone tell you that you should suffer silently or that you should wait patiently for a drug that might never arrive – or might not arrive in time. That just wouldn’t be fair.

Scurvy

You probably know, or at least once knew, that “scurvy” is the name given to the disease caused by vitamin C deficiency.  You might even have heard the story of how a ship’s surgeon performed “the first clinical trial” as a means of discovering that, yes, scurvy results from a lack of fresh fruits – and we’ll get to that in a moment. But before we do, I need to convince you just how bad – how really, really bad scurvy was.

That’s a challenge, because I’m not sure I can imagine myself how bad it was. And I’m not just talking about the disease – which was pretty bad. First you’re tired, then your muscles ache, then you start bleeding in various places where you’re not supposed to bleed – under your fingernails, out your nose, through your legs, etc. Your skin becomes paper thin, your hair falls out, then your teeth fall out, and soon after that you die an exquisitely painful death. Yes, scurvy is, or was, a very nasty disease.

It was also common.  So common that millions are estimated to have perished from scurvy between 1500 and 1900. And not just sailors – landlubbers contracted scurvy as well – though our best records are the logs of ship captains. Here are just a few highlights:

In 1498, Vasco da Gama lost no fewer than 100 of his original crew of 160 to scurvy.

During Magellan’s expedition to the Philippines (1519) he lost 200 of his original crew of 218 to scurvy.

When Commodore George Anson’s flagship sailed from Plymouth in 1741 there were 2,000 men in the fleet. By the time they returned to Britain one year later only 200 living remained: scurvy.

The point is (yes, there is a point) there was a tremendous incentive to discover a means of curing or preventing scurvy. Granted, most of those who died of scurvy were from the lower class, while the decisions were made by the upper class. Still, those were the days when a nation’s strength was defined by its naval power – and naval power required lots of people – living ones. The security of the nation required keeping sailors alive. If for no other reason, you’d think leadership would be desperately searching for a cure and willing to try anything – anything at all. You would be wrong.

So who finally discovered the cure?

James Lind, MD, is often credited with both the discovery of a cure for scurvy and as having performed the first clinical trial. On board ship in 1747 he divided 12 men with scurvy into six groups and administered a different treatment to each group. He noted in his journal that the group receiving lemon juice made “a remarkable and very speedy recovery.” Pretty small trial – but he knew.

Lind published his “Treatise on the Scurvy” in 1753 in which he recommended using lemons and limes as treatment – though he couldn’t explain why. The influential physicians of the day therefore discounted Lind, and the British Admiralty was reluctant to waste money on fruit.

As it turns out, the cure for scurvy had actually been ‘discovered’ several hundred years earlier.

In the winter of 1535 the French explorer Jacques Cartier was stranded with his crew – frozen in the ice off the St. Lawrence River. Scurvy began to afflict the men and it seemed all would perish. But a friendly native showed them a simple remedy. Tree bark and needles from the white pine (both rich in vitamin C) when added to hot water made a tasty beverage that quickly eliminated scurvy.  Upon his safe return, Cartier reported his findings to the leading physicians, but his advice was dismissed. Why would enlightened physicians take advice from “savages.”

The ’science’ of their day prevented them from accepting a very simple solution to an extremely serious problem. Really, all they had to do was try it for themselves to find out. It wasn’t hard. It wasn’t dangerous. Make a tea of pine needles – or have a lemonade. Why wouldn’t they do that? I suppose it must have seemed to them ‘impossible’ that something so simple could alleviate such a horrific problem. How could a lemon save a man from that hideous fate known as scurvy. Bah – it can’t be! So another hundred thousand or so die…

But getting back to the British, and the kingdom

It wasn’t until 1780 that the British finally realized that Lind may have been on to something. And then it was only because his lemonade proposal came from one of greater influence. Gilbert Blane was the personal physician to Admiral Sir George Rodney. War was afoot and the Royal Navy had almost 100,000 sailors at sea. Many of them were slowly dying. Blane studied Lind’s book and quickly realized the importance of that early experiment on two subjects.

Dr. Blane implemented changes (one teaspoon of lemon juice per day, per sailor)  on every ship under his supervision and immediately reduced the death toll from one in seven to one in 20. (Still a rough life at sea.) By 1793, when  France declared war on Britain, Blane had convinced the admiralty to issue lemon juice as a daily ration aboard all ships. Healthy crews led to victory at sea.

The horrific disease known as scurvy – and Napoleon – were both defeated.

By a lemon.