Vitamin D News--it boosts remyelination!

This just in today----

Vitamin D boosts remyelination
Researchers at the University of Cambridge set out to find what controls oligodendrocyte progenator cells (OPCs) ability to differentiate and create myelin--and discovered that it is Vitamin D which binds and activates vitamin D receptors and controls myelin sheath regeneration.  In fact, remyelination of axons is impaired when Vitamin D receptor (VDR) is blocked.  When Vitamin D was added to the brain's stem cells, production of OPCs increased 80%.
http://www.eurekalert.org/pub_releases/2015-12/rup-asf120115.php

In case we need even more proof that Vitamin D is an important part of MS recovery,   I'd like to round up the latest crop of papers, published in 2015,  linking higher Vitamin D levels with better health for people with MS.


Vitamin D prevents brain atrophy
Researchers at Yale University discovered that higher serum levels of Vitamin D is linked to higher levels of gray matter in the brain, and lower rates of tissue loss, or brain atrophy, in MS. They looked at 65 pwMS and measured brain volume on MRI.   The strongest correlation was between low Vitamin D levels and brain atrophy.
http://onlinelibrary.wiley.com/doi/10.1111/ene.12844/abstract

Vitamin D strengthens endothelial cells
A study from the University of Utah found that Vitamin D stabilizes the endothelium and strengthens the vasculature.  It acts directly on endothelial cells to inhibit vascular leak.  Since inflammation and "auto-immune" reactions are a function of plasmic particles leaking into tissue and setting off an immune reaction (in places like the gut or blood brain barrier)---finding ways to strengthen endothelial cells is vitally important.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4607301/pdf/pone.0140370.pdf

Higher Vitamin D levels means more time from RRMS to SPMS conversion
Researchers in the Netherlands found that there was an association of low Vitamin D levels at the start of diagnosis of MS which was linked to an early conversion to SPMS.  Those with higher Vitamin D levels took longer to convert to SPMS.
http://www.ncbi.nlm.nih.gov/pubmed/26598277

Higher levels of sun exposure decreases MS risk
Australian researchers find the UV ray exposure is associated with lower MS progression rates and disease activity, through both Vitamin D and non-Vitamin D pathways.  UV rays modify and regulate immune cells.
http://www.futuremedicine.com/doi/full/10.2217/nmt.15.33


Pretty impressive research!  But are the benefits of Vitamin D for those with MS simply recent news?  Not really.  Dr. Ashton Embry's Direct-MS site is where Dr. Terry Wahls and many of us first heard about the connection between Vitamin D and improved MS outcomes almost a decade ago.  In fact, Direct-MS funded two trials on Vitamin D, and both had very positive results published in 2009 and 2010.  Thanks to the Embry Family for funding and pushing this research!
http://www.direct-ms.org/plannedresearch.html

I've been writing about the therapeutic powers of vitamin D on the vascular endothelium since 2008.  I also included sunshine and UV rays.
 http://ccsvi.org/index.php/helping-myself/endothelial-health

Here's a blog post from 2010, where I explain how Vitamin D provides "vasculoprotection" and prevents brain atrophy.
http://ccsviinms.blogspot.com/2010/07/vitamin-d-provides-vasculoprotection.html

Here's some completely anecdotal evidence from our home:
Jeff's Vitamin D level has stayed around 70ng/mL since he began supplementing and getting rays, and he continues to do well, with no MS progression or disabilities.  His Vitamin D level was at 15ng/mL when diagnosed for MS in 2007.  We had to pay for his first D3 test, since it wasn't covered by insurance. Our doctor asked why we wanted his D3 levels tested, and I shared the Direct-MS site with her.  Since then, our insurance company has seen the light (pun intended!) and covers yearly testing of D3 levels.  As for me, I hadn't been taking any D3 supplements, but that's recently changed. This past spring, my level was 17ng/mL and I was put on a high dose (50,000IU) weekly dosage for 2 months.  My levels are now good at 65g/mL and I maintain that with 4,000IU daily. I have much less arthritis pain and more energy.  There's a link to optimizing Vitamin D levels for healthy people, too.

Also know that there are many environmental factors which can contribute to a lower Vitamin D status- including obesity, older age, living in a more northern latitude with less UV exposure, smoking, skin color and pigmentation, micronutrient and mineral deficiencies (especially magnesium and zinc) and genetic mutations on the Vitamin D receptor (VDR) gene---and all of these factors may influence your serum Vitamin D levels.

So, while this info on Vitamin D is not new or ground-breaking for most following MS research, it is further building on the foundation.  Let this be a shout out to all people with MS.  Find out what your Vitamin D levels are, and make sure you optimize them!  This doesn't always mean simply taking a supplement.  It might involve more sun exposure or phototherapy, quitting smoking, losing weight and eating a whole food diet.  Work with your healthcare provider to establish the best program for you, and get those numbers up!  And don't forget, it's not about one pill or supplement, it's about living a new life.

Be well,
Joan

Melatonin and MS

New research shows the connection between low levels of melatonin, known as the sleep hormone, and MS relapses.

Melatonin is the hormone which helps encourage our sleep state.   It is made by the pineal gland in our brains, and it needs the visual cue of darkness in order to begin production.  We naturally produce more melatonin in the fall and winter months, because darkness is more prevelant.  This is why we might find ourselves sleepier and more likely to want to hibernate during these darker months, because our brain is cranking out melatonin.

New research is linking this lower level of melatonin found in spring and summer to seasonal relapses in MS.
http://www.cell.com/cell/fulltext/S0092-8674(15)01038-7

It appears that in humans with MS, the lower levels of melatonin found in their blood during the sunnier months might be linked to MS progression and relapse rate.  That is, there is a correlation between seasonal low melatonin levels and clinical relapses.  (It's always important to make the distinction between correlation and causation---  the researchers are just noticing that in people with lower levels of melatonin, there were more frequent relapses...but, if you read this whole post, I hope I'll explain why this might be.)  Don't go out and buy melatonin just yet!

The researchers who are studying melatonin weren't quite sure why it is so helpful to people with MS.   So, they go to the EAE model of MS in mice and studying t-cell modulation.  ARGHHH!!!!   Why???

We don't need to look at EAE in mice---we already have a correlation of melatonin levels in brain health for HUMANS.

When we look at MS as a disease like stroke in humans, where hypoxic injury and reperfusion injury damage the endothelial layer of the brain's blood vessels....it all makes sense.

Because melatonin protects the brain's endothelial cells under hypoxic and oxidative stress conditions.
http://www.hindawi.com/journals/omcl/2014/639531/


Melatonin has a cellular protective effect in cerebrovascular and neurodegenerative diseases. Protection of brain endothelial cells against hypoxia and oxidative stress is important for treatment of central nervous system (CNS) diseases, since brain endothelial cells constitute the blood brain barrier (BBB). In the present study, we investigated the protective effect of melatonin against oxygen-glucose deprivation, followed by reperfusion- (OGD/R-) induced injury, in bEnd.3 cells. The effect of melatonin was examined by western blot analysis, cell viability assays, measurement of intracellular reactive oxygen species (ROS), and immunocytochemistry (ICC). Our results showed that treatment with melatonin prevents cell death and degradation of tight junction protein in the setting of OGD/R-induced injury. In response to OGD/R injury of bEnd.3 cells, melatonin activates Akt, which promotes cell survival, and attenuates phosphorylation of JNK, which triggers apoptosis. Thus, melatonin protects bEnd.3 cells against OGD/R-induced injury.

Now in plain English---melatonin protects the endothelial cells of the blood brain barrier, and keeps those endothelial cells alive during times of of low oxygen and low glucose delivery--- so they can protect the brain.  Melatonin is a known anti-oxidant.  Just like fruits and vegetables.  

Another connection could be that people with MS who have lower levels of melatonin just aren't getting enough good sleep---and that could be the connection to higher relapse rates.  Especially now that we understand how the brain's lymphatic cleansing system works only when we sleep.

To complicate and confuse matters---melatonin has an inverse relationship with vitamin D.  In research in people with MS, it was shown that people taking higher Vitamin D supplementation had lower levels of melatonin. 

http://www.ncbi.nlm.nih.gov/pubmed/23665342

But we also know that lower vitamin D rates are correlated with MS relapses.  So, what's a human with MS to do?  Take melatonin???  Bump up vitamin D?  Do both?  How much?  When?  How...?  Light?  Dark?  

Bottom line:  Both melatonin and vitamin D are hormones which are also anti-oxidants, decrease inflammation and address oxidative stress. 

Long-time readers of this blog will know that it's never about one pill or supplement, it's about living a complete lifestyle which encourages endothelial health.   It's all about balance. And there are many ways to accomplish this.  

It's difficult to double-blind and research a complete lifestyle----which is why researchers will pick one aspect at a time---like Vitamin D levels, or melatonin levels, or cholesterol levels.  You get the picture.  

Have your vitamin D levels tested.  If they are low, supplement and get some UV ray therapy.  If you have trouble sleeping, or are jet-lagged,  talk to your doctor about possibly adding melatonin to your regimen.  But remember to move, and eat whole and colorful foods, and laugh, and reduce stress, and get good sleep.  It's a complete lifestyle, and no one pill or supplement can replace that.

Be well!

Joan

Newly diagnosed are healthier today than a decade ago

Dr. Lawrence Steinman recently made a very interesting comment in an article on vitamin D levels in MS progression. (Dr. Steinman, MS researcher and inventor of Tysabri, is now behind the upcoming clinical trial of Lisinopril, an inexpensive generic blood pressure medication, as a treatment for MS.)
 http://ccsviinms.blogspot.com/2013/08/medications-for-ms-addressing-blood.html

Dr. Steinman noted that there has been a decrease in relapse rates in the placebo end of MS drug trials over the last decade.


"I might wonder if these data might explain the progressive decrease in relapse rate in the placebo arm of clinical trials of MS over the past decade. Maybe more and more individuals are aware of vitamin D, and that they are taking vitamin D supplements, thus lowering the relapse rate in placebo arms of trials."
http://www.medpagetoday.com/Neurology/MultipleSclerosis/43899

That's right.
People who are diagnosed with MS today are having less relapses than people diagnosed a decade ago---without being on a disease modifying drug.  These patients were in the placebo end of trials, and not getting the real medication.

What does this mean?  I believe it means the self-help, or "alternative" information is getting out there, thanks to the internet.  People with MS are sharing information, and getting healthier.

When Jeff was diagnosed seven years ago,  I asked his neurologist to test his Vitamin D3 levels.  I had been reading research on Dr. Ashton Embry's website, Direct MS, http://www.direct-ms.org  and wondered about the correlation.  His neurologist said it didn't matter.  Neither did diet or exercise.  MS was an immune-mediated degenerative disease, and there were no scientifically proven means, aside from disease modifying drugs, to slow disease progression.  Case closed.  Good luck.

We got Jeff's GP to order the test, although we had to pay for it, since our insurance didn't cover vitamin D testing.  Sure enough, his level was very low at 15ng/mL  He began to get more sunshine exposure, and take a D supplement w/magnesium and zinc, and the next time he was tested, six months later, his level was at 70ng/mL.  He felt better, too.

And today, we have research showing that Vitamin D levels really do make a difference.  So important, that it is now part of my insurance's paid complete blood testing.  This is new!

But I would submit that it's not just about Vitamin D.

We also have Dr. Terry Wahls, Dr. David Perlmutter, and Dr. George Jelinek sharing their knowledge about nutrition and the importance of a whole food diet and exercise with their large online communities. There are self help groups on websites like This Is MS and Facebook encouraging healthy lifestyles.  Information for newly diagnosed patients now includes nutrition, exercise, Vitamin D, smoking cessation, and stress reduction--and this advice sometimes even comes from the neurologist or the MS Societies.  I hope I've made a small contribution in discussing the endothelium and vascular connection to MS, and by bringing Dr. Zamboni's research to the states and connecting new doctors to the ISNVD.

What a change from only seven years ago!!

When Dr. Roy Swank first noted what he called "capillary fragility" in the 1950s and designed a diet and exercise program to deal with the hypercoagulated blood he found in his MS patients, he was decades ahead of the discovery of nitric oxide and endothelial health.  His patients had fewer relapses and slower MS disease progression in the era before the DMDs.  His contribution to helping MS patients was called "junk science" and he was labled a quack by neurologists.  Yet 60 years later, we see newly diagnosed RRMS patients incorporating whole food diets, vitamin D and exercise--and doing better.

I've said this before, I'll say it again.  Don't wait for your neurologist to tell you that the "science is finally in."  Take your life and health into your own hands today.  Move every day, eat well, get UV rays and supplement D3, laugh and find ways to reduce stress, don't smoke, get a good night's sleep, take care of yourself.

Because in seven years----it may well be a whole new world,
Joan

Vitamin D status and MS--a Five Year Study

A new study from Harvard School of Public Health followed pwMS for 5 years and found that those with increases of 50-nmol/L in average blood vitamin D levels within the first 12 months after diagnosis showed
57% lower risk of new active brain lesions, 
57% lower risk of relapse, 
25% lower yearly increase in T2 lesion volume and 0.41 percent lower yearly loss in brain volume from months 12 to 60.

http://www.eurekalert.org/pub_releases/2014-01/tjnj-vds011714.php

There were 465 patients enrolled in this study, which was originally designed to measure efficacy of beta interferon.   Fortunately, all had at least one measurement of their serum vitamin D status during the time they were followed with neurological exams and MRIs, up to 5 years in total.  The researchers were not supplementing vitamin D, they were simply measuring it, as part of the blood samples they were collecting.

This study is unique, in that it started out as simply a study of beta interferon--and ended up showing that vitamin D status was a very important factor in disease activity.  The researchers measured vitamin D status in pwMS who were a part of this study during their first year, and then followed these patients with MRI and neurological evaluations to see how their MS progressed.  

What can we learn from this study?  Serum vitamin D levels are obviously important in MS disease progression.  The higher blood levels are, the less disease progression, active lesions, brain atrophy, and relapses.

But does this mean that vitamin D supplementation is the only solution?  I would like to encourage more researchers to look at the work of Dr. Richard Weller, a scientist from the University of Edinburgh.  Dr. Weller is examining how vitamin D status serves as a marker of exposure to UV rays.  His research has shown that vitamin D status is closely related to latitude and exposure to sunshine.  Perhaps we need to consider this factor for pwMS.  UV rays release stores of nitric oxide from our tissues, improving endothelial health and the cardiovascular system.

Here is a wonderful TED talk from Dr. Weller on his research.
http://www.ted.com/talks/richard_weller_could_the_sun_be_good_for_your_heart.html


And also today, the results of a new study from Dr. Weller's team and Dr. Feelisch from the University of Southampton.


During the study, the skin of 24 healthy individuals was exposed to ultraviolet (UVA) light from tanning lamps for two sessions of 20 minutes each. In one session, the volunteers were exposed to both the UVA rays and the heat of the lamps. In another, the UV rays were blocked so that only the heat of the lamps affected the skin.

The results suggest that UVA exposure dilates blood vessels, significantly lowers blood pressure, and alters NO metabolite levels in the circulation. Further experiments indicate that pre-formed stores of NO in the upper skin layers are involved in mediating these effects. The data are consistent with the seasonal variation of blood pressure and cardiovascular risk at temperate latitudes.

Professor Feelisch adds: "These results are significant to the ongoing debate about potential health benefits of sunlight and the role of Vitamin D in this process. It may be an opportune time to reassess the risks and benefits of sunlight for human health and to take a fresh look at current public health advice. Avoiding excess sunlight exposure is critical to prevent skin cancer, but not being exposed to it at all, out of fear or as a result of a certain lifestyle, could increase the risk of cardiovascular disease. Perhaps with the exception of bone health, the effects of oral vitamin D supplementation have been disappointing.

"We believe that NO from the skin is an important, so far overlooked contributor to cardiovascular health. In future studies we intend to test whether the effects hold true in a more chronic setting and identify new nutritional strategies targeted at maximizing the skin's ability to store NO and deliver it to the circulation more efficiently."
http://www.sciencedaily.com/releases/2014/01/140117090139.htm



Here is a recent paper from BNAC which looked at vitamin D, sunlight exposure, and brain volume on MRI in people with MS.

Increased summer sun exposure was associated with increased grey matter volume (GMV, r(p)=0.16, p=0.019) and whole brain volume (WBV, r(p)=0.20, p=0.004) after correcting for Extended Disability Status Scale in the MS group. Inclusion of 25-hydroxy vitamin D3 levels did not substantially affect the positive associations of sun exposure with WBV (r(p)=0.18, p=0.003) and GMV (r(p)=0.14, p=0.026) in the MS group.

CONCLUSIONS:

Sun exposure may have direct effects on MRI measures of neurodegeneration in MS, independently of vitamin D.

http://www.ncbi.nlm.nih.gov/pubmed/23385850


I would suggest that worldwide deficiencies in Vitamin D may well be a biomarker of our modern lifestyle.  We spend less time outdoors, and the time we are in the sun, we are covered up with clothing or sunscreen, limiting the amount of UV rays that can penetrate our skin.  This would also further explain the correlation of latitude and MS rates around the globe.  

I've written to and connected Dr. Weller to the researchers at the ISNVD, and encouraged him to reach out to his colleague, Dr. Jim Wilson, who is currently looking at chronic illness in Scotland.  He replied that he is very interested in looking at UV rays in MS, and is currently writing grant applications to study this.  

Something to ponder,
Joan

Seasonal Affective Disorder (SAD) and MS

It's that time of year again!  

The days are shorter.  Sunlight is hard to find.  We bundle up against the cold.  We also put on the extra winter pounds, sleep more and move less.  For those who live in the northern latitudes, the shorter days of winter are a reality.  And this can affect our mood and general health.  As we exercise less, our blood flow slows down. We feel more fatigued, more hopeless. The risk of cardiovascular disease increases.

There is a syndrome doctors know about---called "seasonal affective disorder"  or SAD.  It is very prevelant in northern latitudes.  Most of the association is with mood, or levels of depression.  But it is also linked to cardiovascular disease.

link

What connection does this have with MS?  

MS is a disease linked to northern latitudes, lack of vitamin D and lack of ultraviolet rays.  And we are learning more about the vascular risk.

For 68 years latitude has been identified as an important risk factor in the occurrence of multiple sclerosis (MS), but not satisfactory explanation has been offered for this relationship. Epidemiological studies of MS, however, have failed to take into account the degree of change in the amount of ambient light over the course of the year, a variable which is closely related to photoperiod and latitude. Seasonal affective disorder (SAD), another illness for which latitude is a risk factor, appears to be related to the decrease in ambient light during the winter months, and offers some relevant insights into the geographical distribution of risk for developing MS. 

link

 There is a very strong correlation between UV rays, photorelaxation and cardiovascular disease.

Here's a small sampling on this research.

Dr. Furchgott and the Discovery of Photorelaxation

I've been reading up on the effect of UV rays on the body, and I came back to  the research of Nobel prize winning researcher, Dr. Robert F. Furchgott.  He passed away in 2009, and his university keeps his web page online.  Dr. Furchgott was a professor at SUNY Downstate in Brooklyn, NY---the same place where Dr. Sal Sclafani recently retired and where the first CCSVI conference was held in the US!   Here's Dr. Furchgott's page--

http://www.downstate.edu/pharmacology/faculty/furchgott.html

Dr. Furchgott discovered the process of photorelaxation over 40 years ago.  What he noted in the lab was that exposure to UV rays changed the endothelium, encouraging nitric oxide production and vasodilation of arteries.   

In 2009, before he passed, he stated the current working hypothesis-- 

The present working hypothesis is that light photoactivates some material in the vascular smooth muscle, causing the release of some product which stimulates the guanylyl cyclase to produce cGMP. We are planning experiments to test this hypothesis. One possibility is that the vascular smooth muscle in vivo accumulates some "end pro" formed from the endothelium-derived nitric oxide, and that this product releases NO intracellularly when exposed to the proper wavelengths of light.

Photorelaxation and the Cardiovascular system 

Research into the connection of blood pressure and cardiovascular disease in northern latitudes continues....and the connection appears to be that of nitric oxide and UV rays.

http://circres.ahajournals.org/content/105/10/1031.full

Interestingly, mean systolic and diastolic pressures and the prevalence of hypertension vary throughout the world. Many data suggest a linear rise in blood pressure at increasing distances from the equator. Similarly, blood pressure is higher in winter than summer.3  

++++++++++++++++++++++++++++++++++++++

What can we do about this?  

How can we alleviate SAD, and maybe lessen MS symptoms during the winter months?

I'm going to suggest that for those in the northern latitudes, you might want to look into treatment for Seasonal Affective Disorder.

Talk to you doctor about this, especially before beginning a new exercise program or diet.

Do all you can to keep your vitamin D level optimized, but also look into UV treatment with an approved light box.

Move as much as you are able. Keep exercising, keep the body in motion.

Stick to your healthy diet.  Lots of fresh greens and fruits.  Yes, produce is harder to find.  Move to frozen veggies and fruits- if you're unable to find fresh produce.

If you're feeling depressed, please talk to family members, friends and your doctor.  The "winter blues" are not normal, and could be sign of other issues, like SAD.  There is no need for you to suffer in silence.  

MS is difficult enough.  If the winter months are bringing a worsening of your symptoms, and a change in your mood---please look for help. 

You are not alone.

be well,

Joan

Vitamin D provides "Vasculoprotection"

July 13, 2010 at 10:06am

We all know about the link of low levels of vitamin D associated with MS progression.  The common wisdom is that this is because vit. D modulates the immune system. But now there are more and more studies coming forward showing linkage in other neurological disorders and general brain health via the vasculature.  

Vitamin D supplementation can protects vasculature of the brain.  

Low vitamin D levels are linked to brain atrophy.

From Scientific American:

Low vitamin D in Parkinsons and Dementia--

"The first study, led by Paul Knekt and colleagues at the National Institute for Health and Welfare, Finland, examined levels of vitamin D in the blood of 3,173 Finnish men and women aged 50-79 determined to be free of Parkinson's disease at the start of the study. The researchers then examined the incidence of Parkinson's disease in these participants over a 29-year follow-up period. They found that participants with the highest levels of vitamin D (more than 50 nmol/L) had a 65 percent lower risk of developing Parkinson's disease than those with the lowest vitamin D levels (less than 25 nmol/L).

In the second study, David Llewellyn of the University of Exeter and colleagues examined vitamin D levels among 858 Italian men and women age 65 and older. They found that more than half of the participants with dementia were vitamin D deficient .

___________________________________________________________

And here is news of a study at SUNY Buffalo, from earlier this spring:

"Low vitamin D levels may be associated with more advanced physical disability and cognitive impairment in persons with multiple sclerosis, studies conducted by neurologists at the University at Buffalo have shown.

http://www.sciencedaily.com/releases/2010/04/100429153955.htm

Their results, reported at the American Academy of Neurology meeting, held earlier this month, indicated that:

The majority of MS patients and healthy controls had insufficient vitamin D levels.

Clinical evaluation and magnetic resonance imaging (MRI) images show low blood levels of total vitamin D and certain active vitamin D byproducts are associated with increased disability, brain atrophy and brain lesion load in MS patients.

A potential association exists between cognitive impairment in MS patients and low vitamin D levels."

__________________________________________________________

Now, how could this situation be compounded when we consider CCSVI as a factor in developing MS? I believe it's all about protecting the brain from further vascular damage. Here's a wonderful research paper on how Vitamin D can provide "vasculoprotection" of the brain.

http://ddr.nal.usda.gov/bitstream/10113/27508/1/IND44182071.pdf

"Vitamin D may help to protect against cognitive deterioration and dementia, specifically, vascular dementia and Alzheimer’s disease, through vasculoprotection (Lind et al., 1987; Burgess et al., 1990; O’Connell et al., 1997; Pfeifer et al., 2001; Wang et al., 2001; Zittermann et al., 2003; Wang et al., 2008a,b), preservation of neurons (Sutherland et al., 1992; Landfield and Cadwallader-Neal, 1998; Brewer et al., 2001), and protection against risk factors for cognitive dysfunction (Lind et al., 1987; Burgess et al., 1990; Hypponen et al., 2001; Pfeifer et al., 2001; Li et al., 2002, 2004; Zittermann et al., 2003; Bisc- hoff-Ferrari et al., 2004; Wang et al., 2008a,b).

We did observe an inverse association between 25(OH) D concentration and presence of white matter hyperintensities and large vessel infarcts; indicators of cerebrovascular disease (Buell et al, in preparation). Consistent with this finding, we observed a positive association between vitamin D concentrations and the integrity and structural arrangement of white matter fibers using diffuser tensor imaging. Further studies designed to provide information on the temporal relationship of 25(OH)D and brain morphology are warranted.

420 J.S. Buell, B. Dawson-Hughes / Molecular Aspects of Medicine 29 (2008) 415–422"

The underlying message is, get adequate vitamin D and sunshine. You're helping your brain, and may be slowing or preventing atrophy.

Joan