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I have been under the impression that Vitamin C is generally not recommended for people with MS because it may stimulate the immune system. I started to read more about it and came across this news release. Discovery Shows New Vitamin C Health Benefits

The newest findings explain for the first time how vitamin C can react with and neutralize the toxic byproducts of human fat metabolism.

“This is a previously unrecognized function for vitamin C in the human body,” … “We knew that vitamin C is an antioxidant that can help neutralize free radicals. But the new discovery indicates it has a complex protective role against toxic compounds formed from oxidized lipids, preventing the genetic damage or inflammation they can cause.”

“It’s true that vitamin C does react with oxidized lipids to form potential genotoxins,”…… “But the process does not stop there. We found in human studies that the remaining vitamin C in the body continues to react with these toxins to form conjugates - different types of molecules with a covalent bond - that appear to be harmless.”

In human tests, the OSU scientists found in blood plasma extraordinarily high levels of these conjugates, which show this protective effect of vitamin C against toxic lipids.

“This appears to be a major pathway by which the body can get rid of the toxic byproducts of fat metabolism, and it clearly could relate to cancer prevention.”

Oxidation of lipids has been the focus of considerable research in recent years, the scientists say, not just for the role it may play in cancer but also in other chronic diseases such as heart disease, Alzheimer’s disease, and autoimmune disorders.

The toxic products produced by fat oxidation may not only be relevant to genetic damage and cancer, researchers believe, but are also very reactive compounds that damage proteins

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What are peoples’ thoughts about this news and how Vitamin C may or may not relate to MS? What are the pros and cons of Vitamin C for PwMS? It seems to be a recommended vitamin for people with high cortisol (stress hormone) levels. I’m trying to figure out how to reduce mine (which tested high).

Thanks everyone.

Sharon

It seems to be a recommended vitamin for people with high cortisol (stress hormone) levels. I’m trying to figure out how to reduce mine (which tested high).

You may be interested in reading a book by Dr. Nicholas Perricone entitled The Perricone Prescription. Dr. Perricone is a dermatologist who has focused on controlling inflammatory skin conditions through diet and treatment with vitamins and other supplements such as antioxidants. His book discusses cortisol a great deal. He states that controlling cortisol levels is one of the principle ways to control inflammation. As you may have guessed, many of his recommendations also appear to be good for folks with MS. However, one has to be careful as his book is not directed towards MS and some of his supplement recommendations may be in conflict with the interests of someone with MS.

NHE

Here's a link to a presentation which discusses the antioxidant chemistry of vitamin C and its interaction with vitamin E in repairing lipid peroxyl radicals.

NHE

Here's a journal article about vitamin c that I'm trying to read. About 1/3 of the way into the article it says this in reference to cancer:

Cancer
Vitamin C may protect against cancer through several mechanisms in addition to inhibition of DNA oxidation. One potential mechanism is chemoprotection against mutagenic compounds such as nitrosamines (153, 154). N-Nitroso compounds are formed by reaction of nitrite or nitrate (common in cured food and cigarette smoke) with amines and amides (153). Nitrosating compounds can also be formed from NO generated by inflammatory cells expressing inducible NO synthase (116, 153, 155, 156). N-Nitroso compounds undergo activation by cytochrome P450–dependent enzymes and have been implicated in gastric and lung cancer (153). Epidemiologic studies have shown an inverse association between vitamin C intake, mainly from fruit and vegetables, and cancers at these sites (157, 158); additionally, vitamin C reduces in vivo nitrosation by scavenging nitrite and hence preventing its reaction with amines to form nitrosamines (153, 154). Concentrations of fecapentaenes, fecal mutagens that have been implicated in colon cancer (155), are also reduced by vitamin C (159).

In addition, vitamin C may reduce carcinogenesis through stimulation of the immune system. Two of the major functions of the immune system are to fight off infections and to prevent cancer (3). It is hypothesized that the immune system recognizes tumor-forming cells as nonself. Cytotoxic T lymphocytes, macrophages, and natural killer cells can lyse tumor cells (3). Free radicals and oxidative products secreted by immune cells can also lyse tumor cells. Vitamin C can protect host cells against harmful oxidants released into the extracellular medium. Therefore, an optimal immune response requires a balance between free radical generation and antioxidant protection.

Vitamin C is taken up by phagocytes and lymphocytes to concentrations up to 100-fold greater than in plasma, and intracellular concentrations of vitamin C are reduced when phagocytes are activated (3). Many studies have investigated the effects of vitamin C on leukocyte function; however, the data are inconsistent and conflicting (160). Vitamin C may modulate the functions of phagocytes, such as chemotaxis (161–164), as well as the activity of natural killer cells and the functions and proliferation of lymphocytes (160, 165, 166). Vitamin C may also affect the production of immune proteins such as cytokines and antibodies as well as complement components (160, 167, 168). An important measure of overall immune function is the delayed-type hypersensitivity response, which may be modulated by antioxidant micronutrients such as vitamin C (3, 169). Jacob et al (159) showed that vitamin C deficiency in men ingesting 5–20 mg vitamin C/d for 32 d significantly reduced delayed-type hypersensitivity responses, but resulted in no significant change in lymphocyte proliferation. Delayed-type hypersensitivity responses did not return to baseline, even after supplementation with 250 mg vitamin C/d for 4 wk.

I'm trying to understand the line that I've bolded in green, "Vitamin C can protect host cells against harmful oxidants released into the extracellular medium." In someway I think this may help me to understand if Vitamin C is helpful or harmful for folks who have MS. Can someone who genuinely understands this stuff explain this in english? I'm mostly interested in that one line - but I posted the whole thing in case you need to understand the context to get to the point. thanks, napay

Not everyone thinks Vitamin C is bad for MS you will find many articles with a Google search just put in "vitamin C" "multiple sclerosis" and start there. I have John on Vitamin C a time released one he usually takes 1000mg per day unless he appears to be coming down with something then I bump it up to 3000mg for a few days. I believe and this is just my opinion that we need to have our bodies running at peak performance rather then to suppress the system. I realize copaxone contradicts that statement but it is the path we are on so we have tried to combine the two approaches into one that keeps John running at peak performance so to speak. We had a few close calls this winter where I thought we were heading for a decline but we managed so far to pull John out of both of them within a few days. by bumping up his Vitamin D3, turmeric as well as glucosamine and vitamin C. We have also played with his dosage of lipitor. His last episode was a few weeks back with swallowing problems as well as choking but playing with his vitamins and lipitor has seemed to cure it as he is having no problems now. We are booked for a swallowing assessment this week so might learn more than. I'm crossing my finger's they find nothing. We don't really have a Doctor that sanctions all John's vitamins as I find them disconnected from a natural approach although our neurologist is at least receptive when I make him jot down the information. Our family doctor is still under the impression there is absolutely nothing wrong with John so we should stop looking for trouble. I keep him only because my girlfriend is his receptionist so I have access to all John's files. Plus if I need a test run I can get it ordered in a timely matter. Here is one such article found on Google.

Complementary and Alternative Therapies

A comprehensive treatment plan for MS may include a range of complementary and alternative therapies.


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Nutrition

Eat a diet high in protein and anti-inflammatory oils (nuts, seeds, and cold-water fish); orange, yellow, and dark green vegetables; whole grains in small amounts
Avoid food allergens such as wheat, dairy, eggs, soy, citrus, tomatoes, corn, chocolate, fish, and peanuts—eliminate these foods, then reintroduce one at a time, watching for reactions. Many individuals with MS are sensitive to foods that contain gluten.
Eliminate refined foods, alcohol, caffeine, saturated fats (animal products), and additives (MSG and aspartame)
Potentially beneficial nutrient supplements include the following.

Omega-6 oils (borage, evening primrose, black currant oils) 1,500 mg two to three times per day. Include zinc (30 mg per day) and selenium (200 mcg per day).
B-complex vitamins, especially B12 (1,000 mcg per day) and B6 (100 mg per day), and minerals, such as calcium (1,000 mg per day) and magnesium (500 mg per day)
Vitamin C (250 to 500 mg twice per day), vitamin E (400 IU per day), and coenzyme Q10 (100 mg twice a day)

click here

This is part of my continuing effort to understand Multiple Sclerosis as best as I can. I’m documenting my efforts as I go because I figure there are a few more others like me who would like to try and understand this stuff the way I’m trying to. I’ve made hyperlinks in blue in hopes that this narrative may be more like a beginning than an end. As in my prior posts, I’m not a medical professional, I’m an MS Fiancé and these are my thoughts, and you should see your doctor about medical decisions, yada, yada, yada………………

Starting Point: Two Points of View

My Fiancé has been taking 5 grams (that’s not a typo) of Vitamin C everyday. This concerned me since I know that Vitamin C (also called Ascorbic Acid and hereafter abbreviated AA) is generally associated with boosting the immune system. The recommendation to take all this AA came from the providers of the vitamins, USANA. In a document they call a Technical Bulletin the USANA folks say:

”Since myelin is mostly made of lipids and thus subject to lipid peroxidation, it is theorized that antioxidants can help decrease the damage from free radicals. Nutritional factors capable of influencing lipid peroxidation include the trace element-dependent enzymes glutathione peroxidase (selenium), ceruloplasmin (copper), and superoxide dismutase (zinc, copper and manganese) and nutrients with antioxidant activity such as vitamin C, vitamin E, beta carotene and bioflavonoids.”

On the flip side, the author of “Alternative Medicine and Multiple Sclerosis”, Dr. Allen C. Bowling says:

”The antioxidant vitamins, including vitamins A, C, and E are sometimes claimed to be effective therapies for MS. In fact, there is suggestive evidence that free radical-induced oxidative damage is increased in MS patients and that oxidative damage plays a role in myelin injury as well as axonal damage. However, antioxidant vitamins also stimulate T cells and macrophages; thus, they also pose a theoretical risk.”

Second Point: Details Count, you can’t Generalize

Don’t get all excited; the scientist folks have figured out that AA is needed to make myelin in the lab. The linked article is from the Journal of Cell Biology. I’m going to explain this as best as I can to make sure folks don’t start taking AA because it works in the lab. Taking AA will not grow myelin in your central nervous system. In order to explain this we’ll need some background.

The nervous system is divided into two separate parts, the central nervous system (CNS) and the peripheral nervous system (PNS). The CNS is the brain and spinal cord and the PNS is everything else. In the CNS myelin is made by cells called Oligodendrocytes. In the PNS myelin is made by cells called Schwann cells. In the PNS, the axon and Schwann cells are surrounded by the Basal lamina. Here is a picture. In the PNS, the Basal lamina promotes growth. The spinal cord injury folks are working on ways to use what we know about growing axons/myelin with Basal lamina and Schwann cells for the purpose of growing axons/myelin in the brain and spinal cord, Go Team! See the Spinal Cord Injury article in On the Brain. There are also efforts underway to figure out if Schwann cells can be transplanted into the CNS.

In the CNS there is no equivalent to the Basal lamina. In the CNS AA does not promote myelination. The above referenced article from the Journal of Cell Biology states:

”Oligodendrocytes, which do not form a basal lamina, show no requirement for ascorbic acid in order to myelinate axons in our culture system”

Here is another statement from The Journal of Neuroscience:

” The formation of myelin by oligodendrocytes, which myelinate axons in the CNS without the concomitant deposition of basal lamina, was little affected by ascorbic acid, suggesting that the biosynthesis and assembly of myelin per se does not require ascorbic acid.”

So thus far I’ve established that the AA can’t help make myelin in the CNS because the parts of the body that use AA to make myelin are only in the PNS. Here’s one more thing that I thought was worth knowing: AA cannot enter the CNS because it cannot cross the Blood Brain Barrier. There is a form of AA called Dehydroascorbic Acid that can enter the CNS. But AA cannot. The research folks are looking at this for stuff like stroke, but not MS.

The final detail I want to share is that what is good for one is not necessarily good for the other. In a study of Neurotrophin Nerve Growth Factor, the same substance that was found to promote myelination by Schwann cells was found to reduce myelination by Oligodendrocytes. So now having gone around in a complete circle, I felt that this information was needed since one might otherwise assume that they ought to be taking AA in order to grow myelin in the CNS.

Third Point: So what about this Antioxidant thing?

The USANA folks recommend AA for MS because it is an antioxidant. Right now I have to say that I genuinely have no idea what an antioxidant or a free-radical is. I think I know, I hear about them and folks throw these words around all the time. But when put under the interrogation light, do we really understand the details of this antioxidant and free-radical thing? I don’t, but now I intend to find out.

Let’s start with the term radical. Wikipedia defines “radical” as:

”In chemistry, Radicals (often referred to as free radicals) are atomic or molecular species with unpaired electrons on an otherwise open shell configuration. These unpaired electrons are usually highly reactive, so radicals are likely to take part in chemical reactions. Radicals play an important role in combustion, atmospheric chemistry, polymerization, plasma chemistry, biochemistry, and many other chemical processes, including human physiology. For example, superoxide and nitric oxide regulate many biological process, such as controlling vascular tone. "Radical" and "Free Radical" are frequently used interchangeably, however a radical may be trapped within a solvent cage or be otherwise bound. Historically, "Radical" was used to refer to a collection of atoms that remain unchanged over the course of a reaction, however this usage is, today, uncommon. The first organic free radical (the triphenylmethyl radical) was identified by Moses Gomberg in 1900”

Free radicals come from within the body (endogenous) and from outside the body (exogenous). We commonly think of some of the external sources when we think about free radicals. Some exogenous sources of free radicals are tobacco smoke, organic solvents and pesticides. Here’s an article that includes some discussion about sources of free radicals.

The article is mainly about antioxidant nutrients so you might jump ahead and read it. In an effort to get a list of antioxidants (the stuff we would want to consume for the purpose of reducing the risks posed by free radicals) I linked back to Wikipedia and looked up “antioxidant”. There were a lot of antioxidants listed. I’m not going to discuss them all, but here are the ones that I found interesting in the context of MS:

N-acetylcysteine (pronounced uh-seet-uhl-SIS-tuh-een):
This antioxidant has been found to benefit rats with EAE.

Vitamin A (Retinol, also synthesized by the body from beta-carotene): This antioxidant may inhibit a Th1 response and promote a Th2 response.

Vitamin C (Ascorbic acid): This antioxidant may promote a Th1 response and suppress a Th2 response. (see link for Vitamin A)

Vitamin E, including Tocotrienol and Tocopherol:
This antioxidant may promote a Th1 response and suppress a Th2 response. (see link for Vitamin A)

Curcumin:
This antioxidant has been found to benefit mice with EAE.

So the over all concept is that the free radicals have spare electrons and they tend to get loose. When they get loose they can do harm. The antioxidant compounds work in the body to eliminate the free radical problem. Based on the links above, it’s my best guess that N-acetylcysteine, Vitamin A and Curcumin would be good antioxidant bets for someone with MS. In particular I think N-acetylcysteine is interesting because it may inhibit lipid peroxidation which was the issue that USANA notes as a reason to take antioxidants.

Fourth Point: Stimulation, a bad thing?

You’d think that there would be a LOT of scientific research to show exactly what AA does to make the immune system fight off disease. I’ve looked and this is about the best I can do from the Nutrition Journal:

” There has been a long-standing debate concerning the role of ascorbic acid in boosting immunity during cold infections. Ascorbic acid has been shown to stimulate immune system by enhancing T-cell proliferation in response to infection. These cells are capable of lysing infected targets by producing large quantities of cytokines and by helping B cells to synthesize immunoglobulins to control inflammatory reactions. Further, it has been shown that ascorbic acid blocks pathways that lead to apoptosis of T-cells and thus stimulate or maintain T cell proliferation to attack the infection. This mechanism has been proposed for the enhanced immune response observed after administration of vitamin C during cold infections.”

I couldn’t find anything that solidly explained the effect of AA on macrophages, Th1, Th2, individual cytokines or any other cells that are implicated in current MS thought. Here’s an interesting bit of research that showed that reduction of AA intake inhibited the macrophages ability to migrate.

I’ll speculate that if lack of AA inhibits the macrophage, then additional AA might activate the macrophage. Also, as previously mentioned, AA may promote a Th1 response and suppress a Th2 response. While none of this is conclusive, it seems to me that existing information does not favor taking AA for MS.

Fifth Point: Our Hamster, Our Pet

First of all our family hamster is named JJ. I like JJ and we love to let him run around in a giant plastic ball we have. While I think we make a nice life for JJ, I don’t want to be a hamster, or a lab rat or a researcher’s mouse. The point I’m trying to make is, why settle for less then you have to? Meaning, I don’t see any reason to take something that is potentially risky, when there seem to be alternatives that are potentially a lot less risky. Based on my review, we’ll probably stop taking vitamin C and start taking N-acetylcysteine and beta-carotene.

Second, I did this because I wanted to understand MS better and have a basis for assessing a lot of the claims that are made about supplements. I couldn’t find all this information in one place and it took me about a week to assemble this. So, if it was this much work for me, then I figure I’m helping someone by typing this all up and putting in the links to some of the stuff I looked at.

Thirdly, I hope that you might take this information and use it as a launch pad to gain more information. Be careful about where you get your information. I’ve been careful to put in links so you can assess the accuracy of the information yourself. Sites that hype supplements or that provide testimonials are not very authoritative, they might be attractively persuasive, and they might even have a quote from a doctor, but please learn to discern the examined information from hype.

Fourthly, I know I have not got a complete picture here and that there are some holes. I hope to be corrected. Yes, I admit to being fallible. I will edit this post from your comments. Please post stuff that includes links. Think about the second point before you click the post button. Drop me a message, or post a reply and tell me what you think. napay

IMPORTANT UPDATE: 4/21/06

We did not respond well to discontinuing vitamin C. There has been a clear set back in balance and walking. This prompted me to dig deeper into the Vitamin C issue. I’ve also learned more about MS in writing the 101 post and the the current one I’m working on, a 102 post. Here’s the update.

There is a cytokine called Granulocyte Macrophage Colony Stimulating Factor (GM-CSF). Mice have GM-CSF. When effort was made to induce Experimental Autoimmune Encephalomyelitis (EAE) in GM-CSF deficient mice, The mice proved to be very resistant to developing EAE and its related disability. Meaning, GM-CSF deficient mice did not contract EAE. This implies that GM-CSF may act in a way that enhances the demyelinating activity of MS. This is useful because vitamin C has been found to inhibit the ability of GM-CSF to commnicate.

Nuclear Factor Kappa B (NF-KB) is very difficult to explain. It’s not a cell or cyctokine, it’s something called a “factor” and it’s part of all cells. Here’s an article about NF-KB. It’s a uniquely readable article. The article states:

“NF-kB plays key roles in regulating the expression of many cytokine
genes. Studies on c-rel-deficient mice have demonstrated that c-rel is essential for IL-2, IL-3, GM-CSF, g-IFN expression in T lymphocytes, IL-6 expression in B cells, TNF-a expression in macrophages, and IL-12 expression in dendritic cells.”

I checked Wikipedia to verify what c-rel is, it’s a kind of NF-KB. So this NF-KB is essential for the expression of cytokines IL-2, IFN Gamma and TNF alpha all of which have been implicated in MS. These cytokines are all suppressed by Avonex which is one of the reasons Avonex is used to treat MS. So now here’s the big picture as I see it. Here’s a quote from the end of the article:

“Vitamin C can inhibit the activation of NF- B by two distinct but related mechanisms: down-regulating ROS induced activation and directly inhibiting IKK and IKKß.”

I know that I’ve pasted this together sorta quickly, but for us this means we’re back on vitamin C. You might be wondering about the first batch of arguments I made against vitamin C. There is obviously a choice. IMHO, the strength of the pro-vitamin C arguments are stronger and the fact that I have a bunch of medical journal articles about NF-KB and c-rel v/s a lower volume of info that seems less authoratative (IMHO) going against vitamin C, well, I think it all weighs infavor of taking vitamin C.

Here are 3 more articles that helped me with my discernment:

NF-KB promotes activation of IL-2, IL-3 and GM-CSF
c-rel deficiency increases IL-10 and decreases IL-2, IL-3, GM-CSF and TFN alpha
Th2 produced cytokines, IL-4, IL-11, IL-13 and IL-10 suppress NF-KB activation

Bonus: we found that with vitamin C there was less shot night (Avonex)fatigue/chills reaction. Here's an article that notes that IL-6 might be the cause of shot night fatigue/chills. Here's another article that suggests that vitamin c might inhibit the release of IL-6.

I hope this helps somewhat to make my new opinion more clear.

napay




Other similar posts on my road to understanding MS:
Understanding MS 101: Doctor Talk and People Talk
A Layman’s Review of Glyconutrients – not good
Turmeric, Curcumin and IL-12 - good
C is for Controversy – good

Notasperfectasyou,
Thank you for the excellent discussion of the pros and cons of vitamin C supplements. I thought that I would add some more fuel to the proverbial fire and mention that The Encyclopedia of Healing Foods by Michael Murray states that "blood glutathione levels rose by nearly 50% in healthy individuals taking 500 mg of vitamin C." N-acetyl cysteine is also known to increase glutathione levels and it may be that the higher glutathione levels are what makes n-acetyl cysteine beneficial for MS though I'm not entirely certain about this. Moreover, while n-acetyl cysteine (and glutathione) may have other effects which may benefit MS, they are known to help the liver as glutathione is one of the principal cellular antioxidants. For example, the reason an overdose of acetaminophen is toxic is that its metabolites bind up a large portion of the liver's glutathione which the liver uses to detoxify those metabolites. This leads to oxidative stress and liver damage. Since Ifn-Beta, statins, and possibly other MS medications are hard on the liver, increasing glutathione levels and helping the liver out may be a good thing. My current opinion, which I'm sure some readers will disagree with, is that vitamin C may be ok in moderation, e.g., 250 mg or so though going to extremes with it, e.g., 2000 mg is probably not a good thing.

I also think you did a great job of pointing out that not all antioxidants are created equally. I've mentioned this in a prior thread with regards to grape seed extract which many people take for its antioxidant properties. However, some researchers have shown that it has a tendency to increase levels of Ifn-Gama which would not be good for folks with MS.

Another point of interest is that many of the antioxidants which appear to have anti-inflammatory activity, e.g., lipoic acid, curcumin, epigallocatechin gallate (EGCG from green tea), have also been reported to inhibit the transcription factor NF-kB which produces proinflammatory cytokines. Hopefully with a lower biochemical signal to trigger inflammation there will be lower MS disease activity. However, I don't know if this has been shown in clinical trial though it does seem to be the case in studies of EAE.

NHE

great work, NHE and notasperfectasyou. On behalf of the community, I want to say thanks for your well thought out posts.

I hope this is an appropriate place for my question on Vitamin C. I sheepishly admit my ignorance of chemistry and laziness or lack of knowledge of how to find my own answer.

This stems from my preoccupation with insulin and a "fact" I read somewhere (and, of course, can't remember WHERE) which is floating around in my head (Don't we all have those? Or am I unusual in that?). I think I read that Vitamin C has a chemical formula similar to glucose or sugar; is this so? Unfortunately, I have no friends who majored in chemistry; please point me in a direction to look.

Maybe there is another reason to go easy on the ascorbic acid.

Lynda try here
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I'm not scientific so will try to explain my thoughts on anything that boost the immune system in as simple manner as possible. Lets say we stimulate the immune system exp with vitamin C and it comes out fighting. Much like a room full of 5 year old that you just riled up. The fact that everyone was riled isn't really the problem is it.? The matter is how to get them to stop. One way would be to just never rile them up and keep them calm. The only problem with that is they will never learn to deal with what life hands out. Now what if you gave them the tools to cope and even though it takes lots of work and time in the long run they learn. In fact the 5 year old out grows that stage. Well I've noted since I've been working so hard on minimizing what is toxic in John's particular system his immune system is learning new stuff. I can't believe it but he can sit in a room of flowers now which is something he has never been able to do because of allergies. He can also walk through the perfume department without sneezing. Usually if John was to eat an almond we would be at the hospital with anaphylactic shock yet this Christmas he consumed an olive stuffed with an almond in error(thought it was garlic) and had no reaction at all. His eczema which he had all of his life is 100% gone since last June. His restless leg system is gone 98% of the time and only reappears if totally wiped out. Now John's onset of MS I relate to episodes of anaphylactic shock. These are just thoughts to ponder as we all seem to be looking for answers. What if it is something that simple????