Dietary Supplements and MS

With thanks to some very well informed MS friends here is an extensive list of supplements used to help patients with MS. It includes references to clinical studies, so that you can follow up with your own research.
Even though these supplements are available over-the-counter, please consult with your doctor before taking any of them, or starting any form of  restricted diet.
Low-Fat Diet

The Swank Diet: Between 1949 and 1984, 150 MS patients were directed to consume low-fat diets. Their intake of proteins, fats, and oils was documented, and subsequent disabilities and deaths were noted. The research team found that people who consumed a low-fat diet had less disease progression and increased survival than their counterparts who ate a higher-fat diet (Swank, 1991).

The Best Bet Diet: Ashton Embury in his various esays , booklets and on-line presentations details a form of diet, which, along with suitable supplements, has become known as the Best Bet diet. For more detailed information see the Multiple Sclerosis Resource Centre.

The link between MS and the types and amount of dietary fats consumed has also been established through epidemiological analysis. A high or increased intake of saturated fats, animal fats, and dairy products (another source of saturated fats, except in the case of low-fat dairy products) is associated with an increased risk of developing MS (Agranoff, 1974; Lauer, 1997; Schwarz, 2005; van Meeteren, 2005).


Vitamin D

The incidence of MS increases the farther one lives from the equator, where exposure to ultraviolet light is at its greatest. Growing evidence linking vitamin D and the risk of MS may begin to explain this latitude phenomenon. Studies show that higher sun exposure during childhood and early adolescence is associated with a reduced risk of MS.

A 2004 study found that women who took vitamin D supplements were 40% less likely to develop MS than women who did not take supplements. (However, this study did not provide enough data to conclude that vitamin D has a beneficial influence on ongoing MS.) (Munger, 2004.)

A 2006 study analyzed blood serum stored from military personnel during their service, and found that those with higher levels of vitamin D were at lower risk for later developing MS. This study adds to growing evidence that vitamin D may help protect against the development of MS. (Munger, 2006)

In June 2007, the Canadian Cancer Society said that based on current research, adults should consider increasing their daily dosage of vitamin D. The society said Canadians should now consume 1,000 IU of vitamin D daily during the fall and winter months, in consultation with a health-care provider.

In a small 2009 study, 25 people with relapsing-remitting multiple sclerosis were given a high dose of vitamin D (14,000 international units, IU, each day for a year) and were compared to 24 people who took a lower dose of vitamin D (1,000 IU a day for a year). In the high-dose group, 16% of the people had a relapse, compared to 40% in the low-dose group. As a bonus, the high dose group reported no side effects from the vitamin D supplement.

Cautions:
• Do not take vitamin D if you have hypercalcemia.
• Consult your doctor before taking vitamin D if you are taking digoxin or any cardiac glycoside.
• Only take large doses of vitamin D (2000 international units or 50 micrograms or more daily) if prescribed by your doctor.
• See your doctor frequently if you take vitamin D and thiazides or if you take large doses of vitamin D. You may develop hypercalcemia.
• Chronic large doses (95 micrograms or 3800 international units or more daily) of vitamin D can cause hypercalcemia.


OMEGA-3 FATTY ACIDS

There is considerable statistical evidence that the incidence of MS varies in countries where the diet differs.

Evidence shows that a higher consumption of polyunsaturated fatty acids, especially omega-3 fatty acids, is associated with a decreased risk of MS and slower disease progression in people who have milder forms of the disease (Agnello E et al 2004; Bates D 1990; Swank RL et al 1990; Swank RL 1991; Zhang SM et al 2000). Increased consumption of omega-3 fatty acids may moderate the course of the disease. (Agnello, 2004; Ferrucci, 2005; Nordvik, 2000; Shapiro, 2003).

A 1989 study looked at the long-term effects of omega-3 fatty acids in the treatment of MS, and concluded that there were improvements in the treated group when compared to the control group in terms of duration, frequency and severity of relapses, and the number of patients who either improved or remained unchanged. (Bates, 1989.)

A 2005 study investigated the effects of dietary fat consumption on the course of disease in patients with RRMS. Researchers found that a low-fat diet supplemented with omega-3 fatty acids had moderate benefits in terms of physical components of health status and quality of life. Patients also experienced lower relapse rates while on the supplemented diet than they did in the preceding year (Weinstock-Guttman, 2005).

There are three major types of omega-3 fatty acids that are ingested in foods and used by the body; they are also available as over-the-counter dietary aids:

-- alpha-linolenic acid (ALA), an organic compound found in many vegetable oils, seed oils, nuts and green vegetables;

-- eicosapentaenoic acid (EPA), is obtained by eating oily fish or fish oil—cod liver, herring, mackerel, salmon, menhaden and sardines;

-- docosahexaenoic acid (DHA), is obtained from fish oils; DHA is actively promoted by manufacturers as a food additive. There is less DHA available in the average diet than formerly, due to cattle being taken off grass and fed grain before butchering; likewise, there is less in eggs due to factory farming.

Cautions:
• Consult your doctor before taking EPA/DHA if you take warfarin . Taking EPA/DHA with warfarin may increase the risk of bleeding.
• Discontinue using EPA/DHA 2 weeks before any surgical procedure.

OMEGA-6 FATTY ACIDS

Omega-6 fatty acids are a family of polyunsaturated fatty acids. Blood tests have revealed that MS patients have lower levels of omega-6 fatty acids than people without MS.

-- Linoleic acid is an essential omega-6 fatty acid, found in high concentration in sunflower and safflower oil as well as in lower concentrations in most other vegetable oils; also available as a dietary supplement.

Studies, beginning in the early 1970s, suggest that diets high in linoleic acid can be helpful for MS patients. Patients who supplemented their diet with linoleic acid had longer remissions and reduced the severity of their attacks. A 1984 study reported that some MS patients have abnormally low levels of linoleic acid. (Homa, 1984.)

In another 1984 study, the results of several clinical trials of linolenic acid supplementation for the treatment of MS were evaluated by meta-analysis. The conditions of 87 patients with MS and 85 normal control subjects were assessed for neurological changes over 2.5 years. Patients with low levels of disability at the beginning of the study had a smaller increase in disability over the study period than did the control subjects. In addition, linoleic acid was found to reduce the severity and duration of MS episodes in patients at all levels of the disease (Dworkin, 1984).

The best natural sources for linoleic acid include black currant seed oil and borage oil, both available as dietary supplements. Sunflower seed oil is also rich in linoleic acid and can be used in cooking.

-- Gamma-linolenic acid (GLA) – Another omega-6 fatty acid. Ordinarily, the body makes all the GLA it needs from linoleic acid. But this conversion is occasionally interrupted or inhibited, especially in inflammatory diseases. (Horrobin, 1997, 2000; Jamal, 1994; Kidd, 2001.) Defects in conversion may have a genetic basis, which is thought to predispose some people to inflammatory conditions (Horrobin, 2000).

GLA quells inflammation by competing with pro-inflammatory arachidonic acid. In animals with MS, GLA-fed animals fared significantly better than did control animals (Harbige, 2000).

GLA is available directly from evening primrose oil, black currant seed oil, and borage oil. Most of these oils also contain some linoleic acid.

Cautions:
• GLA should be taken with food.
• Individuals undergoing treatment for cancer should not take GLA (or any other supplement) except under physician supervision.
• Consult your doctor before taking GLA if you take warfarin. Taking GLA with warfarin may increase the risk of bleeding.
• Discontinue using GLA 2 weeks before any surgical procedure.
• GLA can cause gastrointestinal symptoms such as nausea and diarrhoea.

ANTIOXIDANTS

Antioxidants neutralize naturally-occurring but harmful chemicals known as free radicals. MS patients tend to have abnormally low levels of certain key antioxidants. (Mai,1990; Mazzella, 1983; van Meeteren, 2005).

Supplemental antioxidants support cellular antioxidant defenses by scavenging free radicals; reducing inflammatory cell responses by interfering with gene transcription, protein expression, and enzyme activity; and by chelation of metals. Antioxidant therapy in animals with MS has yielded decreases in clinical signs of the disease (van Meeteren, 2005).

-- Selenium, Vitamin C and Vitamin E:

In a small 1990 study, patients with MS were given an antioxidant mixture containing 6 mg of sodium selenite (equivalent to 2740 micrograms of elemental selenium), 2 grams of vitamin C, and 480 mg of vitamin E, once a day for 5 weeks. Although glutathione peroxidase levels were initially lower in patients with MS than in normal control subjects, after 5 weeks of antioxidant therapy, levels of this antioxidant increased 5-fold; side effects were minimal (Mai J et al 1990).

Selenium is available as a dietary supplement, but the best source of natural selenium is Brazil nuts.


N acetyl cysteine (NAC)

NAC is a potent antioxidant. NAC can increase glutathione levels, which increases antioxidant capacity.

MS patients tend to have abnormally low levels of certain key antioxidants, such as glutathione peroxidase (Mai, 1990; Mazzella, 1983; van Meeteren, 2005). Glutathione is available in supplement form, but it is poorly absorbed. A better strategy for increasing the body's supply of glutathione is taking NAC. (Arfsten, 2004; Kidd, 2001).

In animals with MS, NAC has been shown to reduce nitric oxide production in brain-supporting tissues and reduce clinical symptoms and microscopic evidence of brain cell injury and inflammation (de Bustos, 2000; Gilgun-Sherki, 2005; Syburra , 1999).

Cautions:
• NAC clearance is reduced in people who have chronic liver disease.
• Do not take NAC if you have a history of kidney stones (particularly cystine stones).
• NAC can produce a false-positive result in the nitroprusside test for ketone bodies used to detect diabetes.
• Consult your doctor before taking NAC if you have a history of peptic ulcer disease. Mucolytic agents may disrupt the gastric mucosal barrier.
• NAC can cause headache (especially when used along with nitrates) and gastrointestinal symptoms such as nausea and diarrhoea.


Coenzyme q10

Coenzyme Q10 (CoQ10) is another antioxidant of potential usefulness in treating MS and, while there is some debate, its levels may be low in patients with MS (Syburra, 1999). Although CoQ10 has not been investigated specifically for the treatment of MS, it is generally recognized as safe, well tolerated, and potentially useful in the treatment of neurodegenerative disorders.

CoQ10 is a naturally occurring, lipid-soluble antioxidant that serves as a co-factor in the mitochondrial respiratory chain. As an added bonus, CoQ10 is capable of regenerating the antioxidant capacity of spent vitamin E in the body. Decreased levels of CoQ10 are associated with many disease states, including heart disease, cancer, and neurodegenerative diseases (Bonakdar, 2005; Siemieniuk, 2005).

DOSAGE: “I would not feel comfortable recommending to my patients to take more than 50 mg or maximum 100 mg of CoQ10 a day, unless for the temporary treatment of a medical condition.”

“The daily dosage of CoQ10 in healthy individuals is generally in the 15-30 mg range and is taken for general well-being. In patients with heart disease or other chronic conditions, a minimum of 100 mg a day has been used in numerous clinical trials. A dosage in the range of 600-1200 mg is being used in the on-going study on Huntington’s disease, supported by the National Institutes of Health.”

“If on a statin drug, 60 to 90mg per day is suggested.”

Cautions: See your doctor and monitor your blood glucose level frequently if you take CoQ10 and have diabetes. Several clinical reports suggest that taking CoQ10 may improve glycemic control and the function of beta cells in people who have type 2 diabetes.


Lipoic Acid

Lipoic acid, also known as alpha-lipoic acid, is a sulfur-containing fatty acid. It is found inside every cell of the body, where it helps generate the energy that keeps us alive and functioning. Lipoic acid is a key part of the metabolic machinery that turns glucose (blood sugar) into energy for the body's needs.

Lipoic acid is an antioxidant, but unlike other antioxidants, which work only in water or fatty tissues, lipoic acid is unusual in that it functions in both water and fat. By comparison, vitamin E works only in fat and vitamin C works only in water. This gives lipoic acid an unusually broad spectrum of antioxidant action.

Lipoic acid has been studied specifically in MS. Known to cross the blood-brain barrier and to penetrate cellular mitochondria, lipoic acid decreases the activity of intercellular adhesion molecule-1, a small molecule that plays a role in the genesis of MS. It is believed that ICAM-1 and other adhesion molecules are responsible for allowing certain pro-inflammatory immune system cells, namely T-lymphocytes, to cross the blood-brain barrier, paving the way for induction or exacerbation of damage to neurons (Biernacki, 2004; Cournu-Rebeix, 2003; Dedrick, 2003).

In experiments on rodents with MS, lipoic acid produced significant reduction of demyelination and reduced the infiltration of inflammatory T-cells across the blood-brain barrier (Marracci, 2002, 2004; Morini, 2004).

In 2005, in a small clinical trial of lipoic acid in the treatment of patients with MS, thirty-seven patients with MS were randomly assigned to receive various doses of lipoic acid (up to 2400 mg/day) or placebo. Lipoic acid was generally well tolerated and reduced ICAM-1 levels, as well as interfered with T-cell migration into the central nervous system (Yadav, 2005).

There are two types of Lipoic acid: the synthetic S form, and the natural R form. R-Lipoic acid is much more potent (2 times on average) than commonly sold synthetic lipoic acid which contains both the R and S forms of lipoic acid. The S form is chemically the mirror image of the R form of lipoic acid and cannot be used by the body, hence it is useless. Make sure you buy the R form. Fifty mg of R-Lipoic Acid is equivalent to 100 mg of synthetic lipoic acid.

Cautions:

• Lipoic acid may lower blood glucose levels. Consult your doctor before taking lipoic acid if you have diabetes and glucose intolerance; monitor your blood glucose level frequently.


Acetyl L-carnitine (ALCAR)

ALCAR is a derivative of amino acids, naturally produced by the human body. Meat, poultry, fish, and dairy products are the richest sources of L-carnitine. Commercially, it is often marketed as a "life extension" supplement.

A 2004 study showed that acetyl L-carnitine was more effective than amantadine (a prescription drug) for the treatment of fatigue in MS (Thomassini 2004). (Dosage for this trial was 1g twice daily.)

However, the percentage of LCAR that is absorbed when taken via oral supplementation is much lower than that from food sources. In one study, it was shown that approximately 20% of orally supplemented L-carnitine is absorbed, with a bioavailability of roughly 15%, as compared to a bioavailability of between 60% and 75% when absorbed from food.
 
Vitamin B12

Vitamin B-12 is naturally found in foods of animal origin including meat (especially liver and shellfish) and milk products.

When a patient is B-12 deficient, injection is sometimes used if digestive absorption is impaired. There is evidence that injection may not necessary with modern high potency oral supplements (such as 500 to 1000 mcg or more).

Vitamin B-12 is important for the normal functioning of the brain and nervous system and for the formation of blood. Vitamin B12 plays a key role in the generation of myelin. MS and vitamin B12 deficiency share remarkably similar characteristics, occasionally rendering correct diagnosis difficult (Miller, 2005). Some physicians prescribe vitamin B12 supplements for MS patients.

A 1992 study showed that MS patients often have abnormally low levels of vitamin B12 in their cerebrospinal fluid and/or blood serum (Reynolds, 1992).

In a 2001 study, MS patients who received vitamin B12 supplements reportedly experienced consistent clinical improvements in their symptoms (Kidd, 2001).

In a 2002 study, researchers investigated the effects of 6 months of vitamin B12 injections (1 mg/week) on 138 MS patients. Researchers concluded that the patients improved after starting vitamin B12 injections (Wade, 2002).


Glucosamine

Glucosamine, an over-the-counter natural product that has been shown to help with arthritis, may also provide some relief to MS patients.

In a 2005 study, neurologists at Jefferson Medical College, using the mouse model of MS, found that doses of glucosamine similar to those taken for osteoarthritis dramatically delayed the onset of symptoms, and improved the animals' ability to move and walk. The animals’ spinal cords and found less inflammation and “demyelination” in those that were given glucosamine. (Rostami, 2005.)


N-acetylglucosamine (GlcNAc, or NAG)

Previous studies which suggested that glucosamine has some value in the treatment of MS (see above), led Michael Demetriou and colleagues at the University of California, Irvine, to investigate a similar but more potent compound called N-acetylglucosamine (GlcNAc).

In a 2007 study using the mouse model of MS, NAG inhibited the growth and function of abnormal T-cells that incorrectly direct the immune system to attack specific tissues in the body, such as brain myelin in MS.

Defects on cell-surface sugars may promote the short-term inflammation and long-term neurodegeneration that occurs in the central nervous system of MS patients.

Demetriou found that the dietary supplement N-acetylglucosamine (GlcNAc), which is similar but more effective than the widely available glucosamine, corrected defects in protein glycosylation in cells and inhibited inflammatory demyelination in mice. The new study opens the possibility that metabolic therapy with GlcNAc may also prevent neurodegeneration.

The findings suggest that NAG may be useful as an oral therapy to correct neurodegenerational defects and to treat both short-term and long-term symptoms of MS. (Demetriou, 2007.)

Inosine

People who get gout almost never get MS. A 1998 study showed that MS and gout are almost always mutually exclusive; people almost never have both diseases. In a review of 20 million Medicare and Medicaid patient records, researchers discovered almost no overlap between multiple sclerosis and gout. (Hooper, 1998.) This may have something to do with uric acid.

Uric acid is a chemical created when the body breaks down substances called purines. Purines are found in some foods and drinks, such as liver, anchovies, mackerel, dried beans and peas, beer, and wine. Most uric acid dissolves in blood and travels to the kidneys, where it passes out in urine.

If the body produces too much uric acid or doesn't remove enough if it, disease results. Abnormally high levels of uric acid in the body result in a number of disorders including hypertension, cardiovascular disease, renal disease, and gout. A number of studies have shown that MS patients have been shown to have abnormally low levels of uric acid (Peng, 2007 and others).

MS exacerbations are often treated with intravenous methylprednisolone. A 2002 study showed that methylprednisolone therapy increases serum uric acid levels, suggesting that increasing the uric acid concentration may represent one of the mechanisms of action of methylprednisolone in MS patients. (Toncev, 2002.)

Another 2002 study showed that uric acid levels in MS patients correlate with activity of disease and blood-brain barrier dysfunction. (Toncev, 2002.)

A 2008 study noted that “a reduced uric acid concentration has been linked to multiple sclerosis, Parkinson's disease, Alzheimer's disease, and optic neuritis. Historically, uric acid has been considered a marker of these disease states. Recent studies, however, have provided evidence that uric acid may actually play a role in the development or progression of such diseases.” (Kutzing, 2008.)

Uric acid can't be administered orally, because it is degraded by the gastric process before it reaches the bloodstream. However, uric acid levels can be raised by the oral administration of inosine, an over-the-counter supplement.

Two different mechanisms of action have been proposed. First, inosine produces uric acid after ingestion, which is a natural antioxidant; second, it has been shown to induce axonal rewiring in laboratory animals with stroke and spinal cord injury

In a 2006 study, MS patients treated with inosine were found to have a lower relapse rate than non-treated MS patients. (Toncev, 2006.)

Another 2006 study suggests that therapeutic strategies aimed at raising serum uric acid levels may have a neuroprotective effect on MS patients. (Koch 2006.)

In a 2009 study, oral administration of inosine was used to raise serum levels of the natural peroxynitrite scavenger UA in 16 patients with RRMS during a 1-year randomized, double-blind trial. Results showed that increased serum UA levels correlated with a significant decrease in the number of gadolinium-enhanced lesions and improved EDSS.

The only side-effect correlated with inosine treatment was kidney stone formation in 4/16 subjects.