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        Cluster Headache Help and Support >> Medications, Treatments, Therapies >> Functional Hypoxia
        
(Message started by: floridian on Jan 18^th, 2007, 8:50pm)

Title: Functional Hypoxia
Post by floridian on Jan 18^th, 2007, 8:50pm

People here are savvy to the beneficial effects of 100% oxygen, and to the ability of low oxygen levels to trigger a cluster in many people (REM sleep, apnea, high altitude airplanes, etc).

Just came across the idea of functional hypoxia - where oxygen goes in through the lungs, is carried around the bodies, but is not used by the cells. Tissues are gasping for O2 when it is all around them.

This also crosses over with the research on mitochondria and energy deficits in people with CH and migraine - we know something is sluggish in our mitochondria, and that (at least in migraneurs) things like B-vitamins and CoQ10 can both reduce headaches and reduce the energy deficit.

Got me wondering how many people here have this functional hypoxia going on inside, and whether it is a major contributor to CH and a host of other conditions that seem to be common here.

If this idea interests you, check out a series of podcasts from the A4M (American Academy for Anti-Aging Medicine, a board certifying group for doctors). These podcasts are available on iTunes for free, and you don't need an iPod to download them - just the iTunes software (which is also free and runs on any Windows or Mac computer with a sound card).

Title: Re: Functional Hypoxia
Post by tanner on Jan 18^th, 2007, 10:10pm

My ex- boss Dr Robert Springborn, double PHDs from MIT & Penn etc. a very smart but hard to get along with type was very big on the enzyme that you mention Flo, but never told me exactly why.

I know that he belongs to and supports research groups on anti-ageing. Unfortunately like a lot of Mega rich people he never really listened to what any one else was saying unless it was about him so I never was able to pick his brain on the subject.

Oh and he also had the attitude that a "headache" was a sign of weakness and didn't even care to hear about Clusters! "Just do the job and quit whining or find something else to do for a living" Real sweetheart ::)

I would love to know more about what he seemed to think was a "fountain of youth" supplement from someone other then the folks marketing it.

Flo, your up ;)......Tim

Title: Re: Functional Hypoxia
Post by redhead on Jan 18^th, 2007, 10:18pm

Floridian, you truly are my hero. Am interested in your new test theory. Is there also a link here with hypoxia and the need for more water as well as O2?? I wonder because water seems to have some connection with getting O2 used in our bodies. What do you think??

Title: Re: Functional Hypoxia
Post by floridian on Jan 18^th, 2007, 10:35pm

I suspect that the water-water-water treatment probably flushes out chloride and other ions, which could make nerves less excitable. But not sure on that one.

With functional hypoxia, there is plenty of oxygen in the blood, even in most of the cells, but it doesn't get into the tiny mitochondria for some reason - probably related to transport proteins or cell membranes. Pure 100% oxygen could be boosting the levels in the blood enough to push it into the mitochondria in spite of the reduced transport. But oxygen may work (partially or wholly) through other ways - like vasoconstriction.

Title: Re: Functional Hypoxia
Post by georgej on Jan 19^th, 2007, 12:12am

Interesting.

on 01/18/07 at 20:50:15, floridian wrote:

This also crosses over with the research on mitochondria and energy deficits in people with CH and migraine - we know something is sluggish in our mitochondria, and that (at least in migraneurs) things like B-vitamins and CoQ10 can both reduce headaches and reduce the energy deficit.

Will be interested to look at the mitochondrial research--if there were something going on in the mitochondrial DNA, then CH that is inherited should come down through the female line. Anecdotally, at least, that doesn't seem to be the case, although it seems that CH may be weakly inherited from either parent. Perhaps there is something external to the mitochondria affecting its action, or perhaps there needs to be a combination of factors in place before an effect on the mitochondria is noticeable.

Jonathon, can you list a few citations on this so I can read them? Thank you.

Best wishes,

George

Title: Re: Functional Hypoxia
Post by floridian on Jan 19^th, 2007, 8:42am

George,

true that mitochondrial DNA is inherited in a mother-only fashion. But the total function of mitochondria can be affected by traditional XX/XY genetics, nutrition, etc.

Quote:

J Neurol Sci. 1997 Feb 27;146(1):73-80.

Quantitative analysis of skeletal muscle bioenergetics and proton efflux in migraine and cluster headache.

* Lodi R,
* Kemp GJ,
* Montagna P,
* Pierangeli G,
* Cortelli P,
* Iotti S,
* Radda GK,
* Barbiroli B.

Dipartimento di Medicina Clinica e Biotecnologia Applicata D. Campanacci, Universita di Bologna, Italy.

Phosphorus MR spectroscopy (31P-MRS) was used to quantify skeletal muscle bioenergetics and proton efflux in 63 patients with migraine (23 with migraine without aura, MwoA, 22 with migraine with aura, MwA, and 18 with prolonged aura or stroke, CM) and in 14 patients with cluster headache (CH), all in an attack-free period. At rest mitochondrial function was abnormal only in CM, as shown by a low phosphocreatine (PCr) concentration. At the end of a mixed glycolytic/aerobic exercise all three migraine groups showed a significantly smaller decrease of cytosolic pH compared to controls with a similar end-exercise PCr breakdown, while end-exercise pH was normal in cluster headache patients. The normal rate of proton efflux in all headache groups suggests that the reduced end-exercise acidification was due to a reduction of glycolytic flux in migraine patients. The maximum rate of mitochondrial ATP production (Qmax), calculated from the rate of post-exercise PCr recovery and the end-exercise [ADP], was low in cluster headache patients as well as in migraine patients except MwoA. In migraine the degree of the mitochondrial impairment, that apparently is associated with a reduced glycolytic flux, is related to the severity of the clinical phenotype.

PMID: 9077499 [PubMed - indexed for MEDLINE]

Quote:

Brain Res Bull. 2001 Mar 1;54(4):437-41.
Deficient energy metabolism is associated with low free magnesium in the brains of patients with migraine and cluster headache.

* Lodi R,
* Iotti S,
* Cortelli P,
* Pierangeli G,
* Cevoli S,
* Clementi V,
* Soriani S,
* Montagna P,
* Barbiroli B.

Dipartimento di Medicina Clinica e Biotecnologia Applicata D. Campanacci, Universita di Bologna, Bologna, Italy. lodi@med.unibo.it

We used phosphorus magnetic resonance spectroscopy to assess in vivo the brain cytosolic free magnesium concentration and the free energy released by the reaction of adenosine triphosphate (ATP) hydrolysis (DeltaG(ATPhyd)), the latter being an index of the cell's bioenergetics condition. We studied 78 patients with migraine in attack-free periods (7 with migraine stroke, 13 with migraine with prolonged aura, 37 with migraine with typical aura or basilar migraine, and 21 with migraine without aura), and 13 patients with cluster headache. In the occipital lobes of all subgroups of migraine and in cluster headache patients cytosolic free [Mg(2+)] as well as the free energy released by the reaction of ATP hydrolysis were significantly reduced. Among migraine patients, the level of free energy released by the reaction of ATP hydrolysis and the cytosolic free [Mg(2+)] showed a trend in keeping with the severity of clinical phenotype, both showing the lowest values in patients with migraine stroke and the highest in patients with migraine without aura. These results support our current hypothesis that the reduction in free [Mg(2+)] in tissues with mitochondrial dysfunction is secondary to the bioenergetics deficit, and are against a primary role of low brain cytosolic free [Mg(2+)] in causing the bioenergetics deficit in headache.

PMID: 11306197 [PubMed - indexed for MEDLINE]

Quote:

Neurology. 1997 Jan;48(1):113-8. Links
Phosphorus magnetic resonance spectroscopy in cluster headache.

* Montagna P,
* Lodi R,
* Cortelli P,
* Pierangeli G,
* Iotti S,
* Cevoli S,
* Zaniol P,
* Barbiroli B.

Institute of Clinical Neurology, University of Bologna, Italy.

We performed in vivo MR spectroscopy phosphorus (31P-MRS) on the brain and skeletal muscles of 14 patients affected with cluster headache (CH). We examined patients in interictal periods, and also examined nine of them during the cluster period, although not during the attack. Brain 31P-MRS showed reduced phosphocreatine (PCr) levels, an increased ADP concentration (calculated from the creatine kinase equilibrium), a reduced phosphorylation potential, and a high relative rate of ATP biosynthesis (V/Vmax %). The inorganic phosphate (P(i)) content was increased during the cluster period. Ten of 13 patients also showed a slow rate of PCr recovery in muscle after the exercise. 31P-MRS in CH patients showed abnormalities of brain and skeletal muscle energy metabolism comparable with those seen in various types of migraine, thus leading us to suggest a similarity in biochemical pathogenic mechanisms between CH and migraine.

Title: Re: Functional Hypoxia
Post by floridian on Jan 19^th, 2007, 9:15am

Kudzu and the mitochondria? Sure. Can't tell if this is how its work vs. the serotonin thing, or if the two are linked and it is certain serotonin changes that affect the mitochondria.

Quote:

Neurosci Res. 2005 Oct;53(2):183-8.
Protection by puerarin {kudzu} against MPP+-induced neurotoxicity in PC12 cells mediated by inhibiting mitochondrial dysfunction and caspase-3-like activation.

* Bo J,
* Ming BY,
* Gang LZ,
* Lei C,
* Jia AL.

School of Environmental and Biological Science and Technology, Dalian University of Technology, Dalian 116024, China. bojiang0411@yahoo.com.cn

Puerarin, a main isoflavone glycoside distributed in {kudzu} Pueraria lobata (Willd.) Ohwi, showed inhibitory activity on H2O2-induced PC12 cells damage in our previous work. However, there is insufficient evidence in protective mechanism of puerarin, especially that relating to the mitochondrial function. In this study, when cells were pretreated with puerarin prior to 0.4 mM MPP+, protective roles were accompanied by a reduction of cell viability loss, morphological changes of apoptosis and apoptotic rate. To explore the protective mechanism of puerarin in MPP+-induced PC12 cells, mitochondrial function and caspase-3-like activity were measured. The results indicated that puerarin inhibited the release of mitochondrial cytochrome c to cytosol and the loss of mitochondrial membrane potentials. In addition, puerarin also reduced MPP+-induced caspase-3-like activation. Taken together, the above results suggest that pretreatment of PC12 cells with puerarin could block MPP+-mediated apoptosis by mitochondria-dependent caspase cascade.

PMID: 16112764 [PubMed - indexed for MEDLINE]

Title: Re: Functional Hypoxia
Post by BB on Jan 19^th, 2007, 10:29am

Very interesting Flo.

My question is, if the abnormality is at mitochondrial level, why doesnt the same functional hypoxia not triggering a CH hit when a person is out of cycle?

Annette

Title: Re: Functional Hypoxia
Post by floridian on Jan 19^th, 2007, 10:43am

on 01/19/07 at 10:29:51, BB wrote:

Very interesting Flo.

My question is, if the abnormality is at mitochondrial level, why doesnt the same functional hypoxia not triggering a CH hit when a person is out of cycle?

Annette

That is the $64,000 question - does it turn on or become worse in cycle, and why? Or is it always there, making us more susceptible, but something else triggers?

Title: Re: Functional Hypoxia
Post by BB on Jan 19^th, 2007, 11:09am

Another question is mitochondrial DNA and its functions deteriorate naturally with age, yet CH prevalence peaks at a young age ( most commonly starts before 30 ) and actually gets better with age. CH is rare after age 70 and tends to get less severe and less frequent with age instead of the other way round.

Functional hypoxia is also more common in an older person than a younger person, due to various respiratory diseases and with natural aging of body cells.

Therefore if the theory is correct that mitochondrial dysfunction and functional hypoxia is a major factor in triggering CH then shouldnt we see more CH and particularly worsening CH in older people?

[smiley=huh.gif] [smiley=huh.gif] [smiley=huh.gif]

Annette

Title: Re: Functional Hypoxia
Post by floridian on Jan 19^th, 2007, 12:41pm

Good questions - logical, and I don't know the answers.

Just thinking out loud ... while mitochondrial issues do tend to be more common with increasing age, could it be that they occur earlier in clusterheads and then plateau? And with age, something else burns out, and when that goes, the clusters are less likely?

Menopause might be another analogy that gives insight - hormone levels are high. Then at menopause they drop while sometimes fluctuating rapidly, and eventually stabilize at a lower level in post-menopause. During the drop, which can last several years or a decade, the neurovascular symptoms are at their worst (hot flashes, sudden emotional instability, depression etc). When the drop is over, the body eventually adjusts, and those symptoms tend to subside. So it isn't the absolute levels that cause the most visible symptoms, it is the fact that the levels are changing.

Of course, the low hormone levels of old age can increase the risk of problems from osteoporosis to alzheimers to heart disease. But hot flashes are less common in very old women, who have hormone levels even lower than menopausal women.

Title: Re: Functional Hypoxia
Post by nani on Jan 20^th, 2007, 10:26am

This is fascinating (and way over my head, LOL). It caught my attention because at the time of my emphysema diagnosis, the dr said I was hypoxic, and my lungs are really large because of it. My SATs were 98, though. The diagnosis took me by surprise since I really don't have symptoms. The only reason I got an x-ray was because I'm involved in a genetic lung cancer study and every 18 months I go in for blood work and breathing tests. Prior to the last one in Sept, I was still breathing better than people who've never smoked. I tanked on the last one. I have no clue whether this theory applies to me, LOL...but I thought I'd mention it.

Title: Re: Functional Hypoxia
Post by Charlotte on Jan 20^th, 2007, 12:45pm

on 01/19/07 at 11:09:52, BB wrote:

What are you quoting, where did you get this information? I don't want to discourage anyone, but I don't agree.

Charlotte

Title: Re: Functional Hypoxia
Post by kayarr on Jan 20^th, 2007, 11:01pm

What if the lack of oxygen is more critical in a younger person because of more activity? It may make one of the manifestations clusterheadache if there are other variables present.

always thinking;)

Title: Re: Functional Hypoxia
Post by floridian on Jan 21^st, 2007, 12:10am

on 01/20/07 at 12:45:48, Charlotte wrote:

What are you quoting, where did you get this information? I don't want to discourage anyone, but I don't agree.

Charlotte

It certainly is not an absolute truth, but there is a perception among some researchers that cluster headache is most common among young to middle-aged men. Of course, women get them, and not everyone has a reduction with age. But as a general pattern? Some evidence for that.

This Swedish study found that a significant group of patients had only one bout with the beast, and most people seem to have CH for only 3 years or less. Which shifts the statistics towards the idea that clusters get less common with age. Not reflective of what is said here - but it wouldn't be surprising if the regulars here are disprortionately those who get hit more.

Quote:

: Cephalalgia. 2000 Sep;20(7):653-7.

A follow-up study of 60 patients after an assumed first period of cluster headache.

* Sjostrand C,
* Waldenlind E,
* Ekbom K.

Department of Neurology, Huddinge University Hospital, Sweden. christina.sjostrand@neurotec.ki.se

During 1981-96 a series of 60 consecutive out-patients was examined in relation to an assumed first period of cluster headache (CH). On follow up in 1998 we found that six were deceased at a mean age of 56.5 years (range 45-74 years), of whom one had a definitive CH diagnosis and five had one documented headache period only. Six patients were lost to follow up because they could not be reached. In the final group for evaluation (n = 49) it was found that 13 (26.5%) patients had had one cluster period only during a mean observation time of 8.9 years. Out of 36 patients with a definitive CH diagnosis according to International Headache Society (IHS) criteria, 31 patients had episodic CH, four patients had primary chronic CH and one patient had secondary chronic CH. Of the patients with a definitive CH diagnosis, 83% on follow up had had a recurrence of a second period of CH within 3 years or continuous attacks (chronic/semichronic CH) from the onset. Evidently some patients may suffer from one cluster period only. In our patient material only 17% had a second cluster period after 3 years.

PMID: 11128823 [PubMed - indexed for MEDLINE]

Quote:

Cephalalgia. 2001 Apr;21(3):198-200.

New-onset cluster headache in middle-age and elderly women.

Cluster headache is usually considered to affect young men. We hereby report on new-onset cluster headache in middle-aged and elderly women.
...
Cluster headache is commonly considered to be a young-male disorder, but middle-aged and elderly women may also be affected. The characteristics of the pain and its manner of occurrence were similar in our cases to those reported in the young-male population.

PMID: 11442554 [PubMed - indexed for MEDLINE]

This article from Norway might suggest the opposite - if the median age is 47, then half the patients are under 47 and half are older. Which doesn't describe the shape of the curve (which would have to be adjusted to population numbers in each group).

Quote:

Tidsskr Nor Laegeforen. 2000 Nov 30;120(29):3510-2.
[Patients with cluster headache in a neurological department]

...
RESULTS: Median age was 47 years, range 22-78 years.
PMID: 11188375 [PubMed - indexed for MEDLINE]

And those wild and crazy Italians are trying to split CH into two separate subtypes, which have different ages of onset and durations.

Quote:

Cephalalgia. 2000 Nov;20(9):826-9.

Primary and secondary chronic cluster headache: two separate entities?

* Torelli P,
* Cologno D,
* Cademartiri C,
* Manzoni GC.

Headache Centre, Institute of Neurology, University of Parma, Italy. paolatorelli@libero.it

The International Headache Society (IHS) classification divides chronic cluster headache (CH) into two subtypes: chronic CH unremitting from onset (CCHU) and chronic CH evolved from episodic (CCHE).
...

Clinically, CCHE patients exhibited statistically significant differences from CCHU patients, i.e. earlier CH onset and duration of attacks varying more frequently between 120 and 180 min.
...
Based on clinical features, it seems reasonable to suppose that chronic CH may occur as two distinct entities.

PMID: 11167912 [PubMed - indexed for MEDLINE]

One article suggested that age of onset was rarely lower than 14 (hormones, any one?)

Title: Re: Functional Hypoxia
Post by BB on Jan 21^st, 2007, 1:52am

Hi Charlotte,

I am not sure I understand your question, what is it that you disagree with? is it the fact that mitochondrial DNA degenerates with age or that CH tends to decrease with age?

Annette

Title: Re: Functional Hypoxia
Post by Charlotte on Jan 21^st, 2007, 1:34pm

Thank you for the articles, Annette.

I disagree that ch decreases with age. Physically, it is worse.

Psychologically, it is better. I have words to describe what is happening, herbs and meds to lessen the intensity, and a fantastic support group.

Charlotte

Title: Re: Functional Hypoxia
Post by BB on Jan 21^st, 2007, 9:38pm

Hi Charlotte,

I guess we are talking about a different time frame here when we say "age".

By age, I mean older than 70.

It is common knowledge reading most general articles and text books on cluster headaches that the most common age for cluster to start is between 20 and 40. The frequency of the attacks and possibly the intensity of the attacks tend to decrease with age once the person is near the 70 years mark. This is a generalisation and of course there are people whose CH would behave differently. However, it is not common to see full blown active CH in people older than 70.

In general, DNA and mitochondrial DNA degenerate with age, especially from 50 years onwards.

Annette

Title: Re: Functional Hypoxia
Post by Pinkfloyd on Jan 22^nd, 2007, 1:47am

on 01/21/07 at 21:38:57, BB wrote:

However, it is not common to see full blown active CH in people older than 70.

Annette

A recent Norwegian study showed that 41% of male heavy smokers were dead by 70

In the US, the average male life span, is now about 75

Smoking takes off an average of 13 years. (you too ladies)

Maybe the reason it's not common to see people getting "full blown clusters" after the age of 70, is because it's not common to see a "cluster sufferer" LIVE past 70.

Bobw

Title: Re: Functional Hypoxia
Post by BB on Jan 22^nd, 2007, 2:29am

on 01/22/07 at 01:47:10, Pinkfloyd wrote:

OK, thats it everyone ! Stop smoking NOW ! :P 8)

First hurdle : convincing my own husband to stop the ciggy ... ::)

Annette

Title: Re: Functional Hypoxia
Post by floridian on Jan 22^nd, 2007, 8:19am

on 01/21/07 at 21:38:57, BB wrote:

In general, DNA and mitochondrial DNA degenerate with age, especially from 50 years onwards.

That traditionally has been true, for the population as a whole. But it may not describe people with all genetic constitutions, or what happens when diet and lifestyle/environmental factors change.

The 'adult onset' diabetes that used to kick in at age 50+ has shifted to a much younger population. An alarming number of children now have it.

Quote:

Type 2 diabetes, which was once called adult-onset diabetes because it rarely occurred before middle age, is affecting more and more children, some as young as six years.

Exact numbers are still being gathered, but many doctors say there is an epidemic of type 2 diabetes in youth. At the pediatric unit in one diabetes center, staff said they have seen a 10-fold rise in childhood Type 2 diabetes in the past decade.

In type 2 diabetes, which typically occurs beyond age 50 or 60, the body can still make insulin, just not enough.

Title: Re: Functional Hypoxia
Post by georgej on Jan 22^nd, 2007, 8:42am

on 01/22/07 at 08:19:58, floridian wrote:

The 'adult onset' diabetes that used to kick in at age 50+ has shifted to a much younger population. An alarming number of children now have it.

An entirely different, but very interesting topic as well (I'm really getting off topic, I'm afraid)--the changes in disease patterns over time for reasons that are not immediately clear. For example, the incidence of rheumatoid arthritis is generally declining in all age groups--drastically. I haven't read a well-defined idea why that might be.

Best,

George

Title: Re: Functional Hypoxia
Post by floridian on Jan 22^nd, 2007, 9:32am

Speaking of decreasing incidence, how bout them Minnesotans?? An 80% reduction in CH over a 10 year period??

Quote:

Headache. 2005 Mar;45(3):220-3.

Decreasing incidence of cluster headache: a population-based study in Olmsted County, Minnesota.

* Black DF,
* Swanson JW,
* Stang PE.

Department of Neurology, Mayo Clinic of Medicine, Rochester, Minnesota 55905, USA.

The incidence of medically recognized cluster headache within Olmsted County, Minnesota, from 1989 through 1990, was determined by using modified International Headache Society criteria. The results were compared with previously published incidence data from 1979 through 1981. The overall age- and sex-adjusted incidence decreased from 9.8/100,000 person-years in 1979-1981 to 2.07/100,000 person-years in 1989-1990.

PMID: 15836596 [PubMed - indexed for MEDLINE]

Title: Re: Functional Hypoxia
Post by bejeeber on Jan 23^rd, 2007, 12:48am

on 01/21/07 at 13:34:32, Charlotte wrote:

I disagree that ch decreases with age.

Charlotte

Well in my case, after 25 years or so, it has decreased with age. The cycles have decreased in frequency absolutely. Looking forward to complete burnout.

ALthough as far as severity... yeah that got worse, but I'm thinking that's probably courtesy of the meds.....

Title: Re: Functional Hypoxia
Post by mcf69 on Jan 25^th, 2007, 4:29pm

Very interesting stuff Flo, I've studied functional hypoxia a little bit in A&P class, but have forgot most of it. I'll have to study back up on it and get back to you.....