How Vitamin B12 Helps To Reduce Or Prevent Nerve Pain

Today's interesting post from liveitholistic.com (see link below) looks in detail at vitamin B12 and the role it plays in helping with and preventing neuropathy. Many people take vitamin B12 supplements for nerve pain because they've heard or read that it helps but few know why they do. Most neurologists will agree that a vitamin B (and B12 in particular) deficiency can cause nerve damage but it's rare that you see a breakdown of how vitamin B actually works in the body. This is such an article and therefore an important one for neuropathy patients. Well worth a read.

The Importance of B12 and its role in Neuropathy and Anemia. 
Marc Capistrano June 19, 2016
 
The stars have aligned on this post. The topic of B12 keeps coming up lately, and it was a sign that I had to put something up on the blog. The thing about writing is that it’s almost like a personal journal (…here’s what’s on my mind at this point in time and how I feel about it.)

In this case, Vitamin B12 is on my mind!

It’s involved in every metabolic cellular process in our body, DNA production and nerve function to name a few.

A good balance of all b-vitamins is important but B12 tends to get most of the attention because it is not absorbed into the blood stream the same way the other b’s are. B12 is usually more deficient than the other b-vitamins due to a deficiency in Intrinsic Factor. It also binds with “intrinsic factor” (It’s a specialized type of protein produced in the stomach). B12 must be bound to Intrinsic Factor. Then it is absorbed in to the small intestine (There are receptor sites for B12). You need to produce HCL in order to produce intrinsic factor. You also need to produce enough HCL to produce pepsin. Intrinsic (IF) is internally produced. On the other hand, B12 is the extrinsic (outside) factor produced.

Ok Marc. Tell me why B12 vitamins are important.

1. It prevents Peripheral Neuropathy: The myelin sheath acts as an insulating cover over a nerve fiber. It’s through this nerve fiber that conduction impulses are produced and electrical signals are sent and received. Think of it this way, you touch something hot, once the sensation is felt, your nerves send a signal to your brain. This signal works on these conduction impulses. If you don’t know, now you know ***Biggie Voice***.

Well B12 prevents the breakdown of the myelin sheath that covers our nerve fibers (also known as “demyelination”). When we hear myelin sheath, we usually associate this with the brain (MS). But, the myelin is also very important for your spinal cord’s nerve fibers. This damage leads to a condition known as peripheral neuropathy, in which symptoms include loss of coordination, sensory touch and eventual decreased muscle mass.

It’s shown that B12 intake from food and supplementation can improve neuropathy conditions. With issues like tingling, muscular dysfunction and especially neuropathy, it’s best to have a specialist (Chiropractor, Physiotherapist) look at you and make a proper diagnosis. As a nutritional practitioner, my job is to support the physical intervention through nutrition once a person is diagnosed.

2. The effects of B12 deficiency can cause irreversible symptoms: This is seen in Multiple Sclerosis (a degenerative disease of the nervous system). As with any tissue in the body, once it’s damaged, scar tissue forms (also known as Sclerosis).

3. A lack of B12 can lead to Pernicious Anemia: This is a form of anemia caused by a lack of absorption of B12 due to a deficiency in Intrinsic Factor. B12 binds with “intrinsic factor” as I had mentioned earlier. Without B12 and Intrinsic factor, the membranes of immature red blood cells rupture, disintegration of the stomach lining can occur which can lead to autoimmune diseases such as Crohn’s disease.

4. It makes us happy: B12 plays an important role in supporting and assisting with the formation of neurotransmitters such as serotonin and dopamine production. And this, make us happy…

5. B12 helps us recycle Homocysteine: Anyone out there with a history of cardiovascular disease will have some knowledge of homocysteine levels. If you don’t, then just know that homocysteine is created as a by-product of our body’s metabolism of methionine and cysteine.

Homocysteine isn’t all bad, it still gives us things like Cysteine, which is a precursor to glutathione (an amino acid known for its detoxification capabilities) and is important to the synthesis of Neurotransmitters. The only problem is that high levels of homocysteine are indicative of cardiovascular and neurodegenerative diseases. B12 is important in taking homocysteine and converting it back to methionine.

Ok…What do I do?

Before we get into the details of B12 intake, it’s important to note that all b vitamins including B12 are depleted in the body by things like stress, birth control pills and high intake of sugars.

1. Some people can’t produce Intrinsic Factor. If this is the case, B12 shots are available. You’ll want to buy Methylcobalamin (the active form), not Cyanocobalamin.

2. HCL (stomach acid) is required in order to take B12 from its protein carrier Intrinsic Factor. Refrain from antacids and supplement with Hydrochloric acid with betaine to improve stomach pH.

3. If you’re simply deficient and looking for the next best thing to a shot, then a sublingual (under the tongue) is another alternative option. This skips the digestion process and gets right into the bloodstream. People looking to simply optimize or increase B12 intake can take a Vitamin B complex with a higher B12 content.

4. B12 food sources: Liver, Meat Protein, Dairy, and Seafood (particularly shellfish).

5. The liver has to activate B-vitamins. If you have an under functioning liver, then B-vitamins are not being absorbed. Support the liver, and the b-vitamins will follow!

6. Supplements and B12 aside, it’s important to look at the root cause of demyelination (breakdown of the nerve fiber). In some cases, autoimmune conditions cause the self-destruction of the myelin sheath. Eliminating triggers that cause chronic inflammation (high sugar, poor diet etc.…) can prove to be your best prevention and early treatment. The entry of pathogens through the blood brain barrier affects the CNS, which in turn affects the peripheral system. Boosting your immune system can also be a great way to properly limit the amount of sclerotic tissue that forms.

http://www.liveitholistic.com/blog/2016/6/19/the-importance-of-vitamin-b12-and-its-role-in-neuropathy

BREATHE EASIER GET YOUR VITAMIN D

Asthma, which inflames and narrows the airways, has become more common in recent years. While there is no known cure, asthma can be managed with medication and by avoiding allergens and other triggers. A new study by a Tel Aviv University researcher points to a convenient, free way to manage acute asthmatic episodes -- catching some rays outside.

According to a paper recently published in the journalAllergy, measuring and, if need be, boosting Vitamin D levels could help manage asthma attacks. The research, conducted by Dr. Ronit Confino-Cohen of TAU's Sackler Faculty of Medicine, Meir Medical Center, and the Clalit Research Institute, and Dr. Becca Feldman of the Clalit Research Institute drew on the records of millions of patients and used physician diagnoses, rather than self-reports, for evidence of asthma episodes.

"Vitamin D has significant immunomodulatory effects and, as such, was believed to have an effect on asthma -- an immunologically mediated disease," said Dr. Confino-Cohen. "But most of the existing data regarding Vitamin D and asthma came from the pediatric population and was inconsistent. Our present study is unique because the study population of young adults is very large and 'uncontaminated' by other diseases."

A broad study

Dr. Confino-Cohen and her team of researchers analyzed the medical records of nearly four million members of Clalit Health Services, Israel's largest health care provider. The Vitamin D levels of 307,900 people were measured between 2008 and 2012. Researchers also took into account key predictors of asthma, such as obesity, smoking, and other chronic diseases. Of some 21,000 asthma patients in Israel studied, those with a Vitamin D deficiency were 25 percent more likely than other asthmatics to have had at least one flare-up in the recent past.

The researchers found that Vitamin D-deficient asthmatics were at a higher risk of an asthma attack. "Uncontrolled asthma" was defined as being prescribed at least five rescue inhalers, one prescription of oral corticosteroids, or visiting the doctor for asthma at least four times in a single year.

"Our results add more evidence to the link between Vitamin D and asthma, suggesting beneficial effects of Vitamin D on asthma exacerbations," said Dr. Confino-Cohen. "We expect that further prospective studies will support our results. In the meantime, our results support a recommendation for screening of Vitamin D levels in the subgroup of asthma patients who experience recurrent exacerbations. In those with Vitamin D deficiency, supplementation may be necessary."

Sunny side up?

While most of the Vitamin D in people's bodies comes from exposure to the sun, dermatologists recommend obtaining the ingredient from other sources -- fish, eggs, cod liver oil, fortified milk, or a dietary supplement -- due to the dangers of overexposure to the sun.

"We know a lot about this disease and many therapeutic options are available. So it's quite frustrating that the prevalence of asthma is not decreasing and many patients suffer exacerbations and significant impairment in their quality of life," Dr. Confino-Cohen, an allergy and clinical immunology specialist, said. "Increasing Vitamin D levels is something we can easily do to improve patients' quality of life."

Based on the findings, the researchers recommend that people whose asthma cannot be controlled with existing treatments have their Vitamin D levels tested. For those with a vitamin D deficiency, supplements may make sense.

"This study provided an exceptional opportunity to research asthma. I received a research grant from Clalit Health Services, which provided us with the opportunity to use their very large database and to conduct the study with the professional staff of Clalit Research Institute," said Dr. Confino-Cohen. "We anticipate further prospective research that will support our findings and open a new treatment modality to the population of uncontrolled asthmatics."

Low Vitamin D Levels And Forms Of Neuropathy

Today's post from autoimmunegal.blogspot.com (see link below) refers specifically to Vitamin D deficiency and Sjogren's Syndrome (a systemic autoimmune disease in which immune cells attack and destroy the glands that produce tears and saliva. It is also often linked to rheumatic disorders). Normally the body makes its own vitamin D with exposure to the Sun. The article also talks about the links between low Vitamin D levels and neuropathy. If you have an auto-immune disease/condition, it's possible that you also have low vitamin D levels. That's by no means a certainty but recently research has shown the importance of a stable Vitamin D levels for various medical reasons. People with HIV for instance also often have vitamin D deficiencies, often due to the medications, sometimes leading to, amongst others bone density problems but also peripheral neuropathy. It seems to be one of those subjects that's gaining steam across the internet and it is clear that more research needs to be presented to show how and why vitamin D levels have an effect on auto-immune diseases. In the meantime, if your doctor is willing it will do now harm to check your D levels (along with B12 and others) if you have neuropathic problems.
 

  
Sjogren’s, Vitamin-D, Neuropathy, and Lymphoma
Friday, December 7, 2012

Those of you who follow me on twitter (@autoimmunegal) know that I am always tweeting health and medical research studies on autoimmune diseases. Yes, that may make me a little bit of a nerd, but that is OK with me. Along those lines, I recently came across an interesting study (thanks to a tweet from the Sjogren’s Society of Canada) that I thought was very important to share. This study from the Journal of Autoimmunity found a link between primary Sjogren’s Syndrome (pSS) patients with low vitamin-D levels having peripheral neuropathy and having lymphoma.

It is important to mention that this research is the first to find a relationship between low vitamin-D and the risk of lymphoma for those with Sjogren's. There have also been very few studies to date examining vitamin-D levels and their impact on Sjogren's patients. The authors write with regard to neuropathy that “vitamin-D deficiency may be a component in the pathogenesis of neuropathy in pSS.” They then conclude that their research “may warrant the need for a tighter monitoring of vitamin-D among patients with pSS." You can see the article's abstract by clicking here.

Low vitamin-D levels have been correlated with autoimmunity in some studies. In addition, vitamin-D has been found to have a protective effect in preventing the development of AI diseases such as lupus, rheumatoid arthritis, autoimmune thyroiditis, and Type 1 diabetes. Some studies have even shown that higher levels of vitamin-D are associated with decreased cancer risk including for non-Hodgkin’s Lymphoma, but as is often the case with scientific research there have been conflicting studies and controversy in this area. Basically vitamin-D seems to be powerful stuff.

When I was diagnosed with Sjogren’s almost two years ago, I was found to have both low vitamin-D levels and severe neuropathy. This study might shed some light on patients like me and serves as big reminder that I best keep taking my vitamin-D supplement. I take a daily over the counter supplement and I do try to have foods high in vitamin-D a few times a week, but that doesn't always raise my vitamin-D level high enough. When my levels are low, my doctor usually prescribes a 12 week course of 50,000 IU of D3 once a week. That usually does the trick to get my vitamin-D in normal range.

The results of this study certainly gives me and others with Sjogren’s MAJOR reasons (lymphoma and neuropathy) to talk to our doctors about vitamin-D and take our supplements if they recommend it. I actually haven’t had my vitamin-D levels (a simple blood test) checked in some time so that will be added to the list to discuss for my next rheumatology appointment in a couple months. If you want to read more about vitamin-D and autoimmune diseases, check out some of the links I listed below (please feel free to add your own as this list is far from comprehensive). To learn more about lymphoma and Sjogren’s, click on this link to a recent post from Julia’s blog 'Reasonably Well' on the topic.

Were your levels of vitamin-D low when you were diagnosed with autoimmune disease? By the way, make sure to talk your doctor before making any changes to your vitamin supplements.

http://autoimmunegal.blogspot.nl/2012/12/sjogrens-vitamin-d-neuropathy-and_7.html

WINTER RELATED ATOPIC DERMATITIS VITAMIN D HELPS

A study conducted in more than 100 Mongolian schoolchildren found that daily treatment with a vitamin D supplement significantly reduced the symptoms of winter-related atopic dermatitis, a type of eczema. Led by a Massachusetts General Hospital (MGH) physician, the report in the October issue of the Journal of Allergy and Clinical Immunology supports the results of a preliminary study that showed similar results in a small group of children in Boston

While we don't know the exact proportion of patients with atopic dermatitis whose symptoms worsen in the winter, the problem is common," says Carlos Camargo, MD, DrPH, MGH Department of Emergency Medicine. "In this large group of patients, who probably had low levels of vitamin D, taking daily vitamin D supplements -- which are inexpensive, safe and widely available -- proved to be quite helpful." Camargo led both the earlier Boston pilot study and the current investigation, which was performed in collaboration with investigators from the Health Sciences University of Mongolia.

A chronic inflammatory disorder of the skin, atopic dermatitis is uncomfortable and makes patients more vulnerable to bacterial infection. Symptoms of the disorder -- most commonly seen in children -- often worsen during wintertime. While controlled administration of ultraviolet light, which can stimulate the production of vitamin D in the skin, is a common treatment for severe atopic dermatitis, the possibility that vitamin D deficiency contributes to the seasonal worsening of symptoms had received little consideration prior to the Boston study. That investigation involved only 11 children but provided preliminary support for the hypothesis.

The current study, conducted in collaboration with the National Dermatology Center in Mongolia, enrolled 107 children, ages 2 to 17, from nine outpatient clinics in the capital city of Ulaanbaatar. The participants -- all of whom had a history of atopic dermatitis symptoms worsening either during cold weather or around the transition from autumn to winter -- were randomly divided into two groups. One group received a daily vitamin D dose of 1000 IU while the other received a placebo -- both delivered in odorless, colorless and tasteless drops. Neither the children's parents nor the study investigators knew to which group participants had been assigned.

Standard evaluations of atopic dermatitis symptoms were conducted at the outset of the trial and at the end of the month-long study period, and parents were also asked whether they saw any improvement in their child's condition. At the end of the month, children receiving the vitamin D supplement had an average 29 percent improvement on the primary assessment tool used, compared with 16 percent improvement in the placebo group. Additional assessments -- including the report from parents -- also showed significantly greater improvement among children receiving vitamin D.

While data gathered at the outset of the study could not determine whether or not participating children were deficient in vitamin D, the authors note that an even larger study of Ulaanbaatar children conducted at the same time found significant vitamin D deficiency in 98 percent of participants, supporting the probability that the children in this study were also deficient. While future studies are needed to assess the value of vitamin D treatment in adults and in children with year-round symptoms, Camargo -- a professor of Medicine at Harvard Medical School -- says that parents of children with symptoms that worsen in the winter should try a vitamin D supplement for a few weeks when symptoms flare to see if it helps. He encourages parents to discuss this study and their plan with their primary care provider.

How Long Should You Supplement Vitamin D To Ease Neuropathy

Today's post from tapintegrative.org (see link below) tries to answer the question in the post title by looking at recent research studies. It won't surprise you to see that it's aimed at diabetics with neuropathy but as you will all know by now, it applies to most cases of neuropathy with the same symptoms. There's a lot of information on the Net at the moment about vitamin D - it seems to be the buzz vitamin of the year! This study however, basis its conclusions on an actual study and explains how the vitamin may work for nerve damage patients. It concludes that short-term supplementation with vitamin D can indeed reduce nerve pain noticeably but points out that this study should also serve as a basis for research into long-term use of the vitamin. Judging by other articles, if you're deficient in vitamin D, supplementing it will benefit you across a range of health issues. The key is whether you're deficient or not and a test will sort that out - otherwise you may be throwing your money away supplementing a vitamin you don't need.

Short Term Vitamin D Supplementation Eases Diabetic Neuropathy
Date Posted: 9/24/2015 

Diabetic peripheral neuropathy (DPN) is a long-term complication of type 2 diabetes that causes nerve damage so severe that quality of life in these patients plummets. Considering that most type 2 diabetics are also deficient in vitamin D and that low levels of the nutrient are associated with DPN severity, a research team from Kuwait investigated the effect of vitamin D supplementation on DPN. Their results, published in the journal Medical Principles and Practice, found that even a short-term course of oral vitamin D supplementation eased DPN pain. It seems that simply boosting vitamin D levels in these patients had a profound effect on their health and well-being.

To examine the relationship between vitamin D and DPN, the research team conducted a prospective, placebo-controlled trial that included 112 type 2 diabetic patients with DPN and vitamin D deficiency (defined as total serum vitamin D levels below 20 ng/mL). The participants were randomized to the treatment group (n=57) or a placebo group (n = 55). At baseline, presence and severity of DPN were measured via neuropathy symptom score (NSS), a neuropathy disability score (NDS), and a nerve conduction study (NCS). Changes in NSS and NDS were to be the primary outcome with change in the NCS as the secondary outcome. In the treatment group, participants took oral capsules containing 50,000 IU vitamin D once per week, and the control group took placebo capsules once per week.

After 8 weeks, each participant’s level of vitamin D was measured again. In the vitamin D‒supplemented group, 38 participants (66.7%) reached sufficient vitamin D status, which means their D levels measured above 20 ng/mL. Overall, the treatment group saw a significant 13.12 ng/mL increase in vitamin D levels compared to the 1.1 ng/mL increase in the placebo group. Interestingly, NSS values improved significantly in the treatment group vs the placebo group (‒1.49 ± 1.37 vs ‒0.20 ± 0.59, P less than 0.001); however, no improvement was observed for NDS and NCS values.

While these findings are encouraging, it’s difficult to ignore the absence of change in NDS and NCS values between the 2 groups. This surprising result may be due to the short period of treatment in the trial, given that DPN is a chronic disorder that develops over years. In other words, it may just take longer than 8 weeks of vitamin D supplementation for shifts in these parameters to be discernible. Therefore, this short-term study should serve as a catalyst for future studies to test the effect of vitamin D over longer periods of time on the relief of DPN pain.

Source: Shehab D, Al-Jarallah K, Abdella N, Mojiminiyi OA, Al Mohamedy H. Prospective evaluation of the effect of short-term oral vitamin D supplementation on peripheral neuropathy in type 2 diabetes mellitus. Med Princ Pract. 2015 Feb 26. [Epub ahead of print]

http://www.tapintegrative.org/Blog/September-2015/Vitamin-D-Supplements-Ease-Diabetic-Neuropathy

Why Do We Take Extra Vitamin B For Neuropathy

Today's post from onlinelibrary.wiley.com (see link below) is an important one for several reasons, not least of which is how it shows readers how complex medical studies are set up and planned. It also questions the role of Vitamin B (in all its forms) in neuropathy treatment. It is true, wherever you look on the internet, you will see articles blithely recommending vitamin B supplementation as an answer to neuropathy symptoms and this has resulted in patients rushing to health food shops and supermarkets to stock up on vitamin B supplements. The problem is that serious studies into vitamin B supplementation are conspicuous by their absence, although occasionally, you'll see a vague warning not to 'overdose'. The most important lesson from all this is that you should only ever supplement an existing deficiency and how will you know you're deficient in vitamin B unless your doctor tests you for it? 90% of the time, patients look at the disease and wrongly conclude that extra vitamin B is the answer, without finding out the levels in their own bodies. Apart from this; which sort of vitamin B are you going to choose...and why. You'll often see vitamin B12 being recommended; or Bi, B2 etc etc, or combinations of B compounds. You get the picture!
This article refers to a study begun in the middle of last year intended 'to assess the effectiveness and safety of vitamin B supplements for the management of pain and nerve damage in people with diabetic peripheral neuropathy.' It also examines the various sorts of vitamin B and explains their purpose. Pretty important don't you think and hopefully it's just the first of many serious studies into supplements and nerve damage. The problem is that when people exhaust all the standard chemical options and the symptoms continue, their next port of call is the supplement industry and its all too voracious marketing campaigns. There's nothing wrong with that, as long as you do your research first and consult your doctor and then stop the supplement if it's having no effect!! Otherwise you're sticking a pin in the ever-growing supplement list and hoping for the best...never the healthiest option...I'm sure you agree.

Vitamin B for treating diabetic peripheral neuropathy
Hanan Khalil, Helen Chambers, Vivian Khalil, Cynthia D Ang

First published: 8 June 2016
Editorial Group: Cochrane Neuromuscular Group
DOI: 10.1002/14651858.CD012237View/save citation
Cited by: 0 articles

Abstract

This is the protocol for a review and there is no abstract. The objectives are as follows:

To assess the effectiveness and safety of vitamin B supplements for the management of pain and nerve damage in people with diabetic peripheral neuropathy.

Background
Description of the condition

Peripheral neuropathy is the most common risk factor for foot ulcers in people with diabetes (Duby 2004). More than 80% of all non-traumatic amputations in diabetic patients are the result of foot ulcers (Singh 2005). In 2010, the estimated world prevalence of diabetes was 285 million, a figure expected to rise to 439 million by 2030 (Shaw 2010). Diabetic peripheral neuropathy (DPN) is then expected to affect around 236 million, constituting a major cause of mortality and morbidity, with a significant associated financial cost (Tesfaye 2012). The annual cost of DPN in the United States was estimated to be USD 10.9 billion in 2010 (Gordois 2003; Zhang 2010).

Diabetic neuropathy can be divided into four broad patterns, depending upon which nerves are affected: DPN, proximal neuropathy, autonomic neuropathy, and focal neuropathies (American Diabetes Association 2014; Boulton 2004). Diabetic neuropathy affects long fibres first, including the feet and distal legs. Proximal neuropathy is often asymmetric and may involve the thighs, hips, or buttocks. Autonomic neuropathy can cause dysfunction of the gastrointestinal system, blood vessels, and urinary system, and sexual dysfunction. Focal neuropathies often occur at common sites of nerve compression and affect nerves such as the ulnar and median nerves in the arm, the peroneal nerve in the leg, nerves of the thoracic and lumbar regions, and specific cranial nerves (Boulton 2004).

The American Diabetes Association has defined DPN as “the presence of symptoms and/or signs of peripheral nerve dysfunction in people with diabetes after the exclusion of other causes” (American Diabetes Association 2014). Symptoms of DPN include numbness or reduced ability to feel pain, muscle weakness, difficulty walking, and serious foot problems (Boulton 1998; Hughes 2002; Huskisson 1974).

No gold standard for diagnosing DPN exists; the history and physical examination are key, as the diagnosis remains clinical (American Diabetes Association 2014). Supportive semi-quantitative testing, such as monofilament testing (using von Frey hairs), nerve conduction studies, electromyography, and quantitative sensory testing, can also be used (Bril 2013). Exclusion of non-diabetic causes should also be undertaken, again through history, examination, and the judicious use of investigations such as serum vitamin B₁₂, thyroid function tests, blood urea nitrogen, and serum creatinine (Perkins 2001).

Early diagnosis and management of DPN are crucial for the prevention of amputations, foot ulcers, and other injuries. Successful diagnosis and management require early screening for high-risk individuals (American Diabetes Association 2014; Khalil 2013a).

Treatment of DPN is multifaceted: components include stable glucose control; regular physical check-ups including foot care; patient education; and specialist care when needed (Callaghan 2012). Pain management includes the use of medications such as, for example, pregabalin, sodium valproate, dextromethorphan, tramadol, opioids and, in some cases, topical capsaicin and lidocaine (Khalil 2013b).

Description of the intervention

The B vitamins comprise eight water-soluble compounds that have essential roles in cell metabolism: vitamin B₁ (thiamine), vitamin B₂ (riboflavin), vitamin B₃ (niacin, niacinamide, or nicotinic acid), vitamin B₅ (pantothenic acid), vitamin B₆ (pyridoxine, pyridoxal, pyridoxamine, or pyridoxine hydrochloride), vitamin B₇ (biotin), vitamin B₉ (folic acid) and vitamin B₁₂ (hydroxycobalamins, cobalamins). Each one of these components has a different physical and chemical structure and completes an essential function in the human body (Chaney 1992; Olson 1996).

Vitamins B₁, B₂, B₃, and biotin are involved in energy production; vitamin B₆ is required for amino acid metabolism. Thiamine is converted to thiamine pyrophosphate which has a role in carbohydrate metabolism. Thiamine pyrophosphate also plays a role in the transmission of nerve impulses. Riboflavin is converted into flavin mononucleotide and flavin adenine dinucleotide that serve as coenzymes for respiratory flavoproteins. The active forms of nicotinic acid are coenzymes for proteins that catalyse oxidation-reduction reactions in tissue respiration (Chaney 1992; van Boxtel 2001).

Vitamin B₆ is converted to pyridoxal phosphate and is involved in the metabolic transformations of amino acids and in the metabolism of sulphur-containing and hydroxyl-amino acids. Pyridoxal phosphate is required for the synthesis of sphingolipids for myelin formation. Vitamin B₁₂ has several congeners: cyanocobalamin, hydroxocobalamin, methylcobalamin, and 5’-deoxyadenosylcobalamin. Vitamin B₁₂ and folic acid facilitate essential steps in cell division (Chaney 1992; Hillman 1996).

Common vitamin B deficiency features include peripheral neuropathy, depression, mental confusion, lack of motor co-ordination, and malaise. Vitamin B deficiencies cause various diseases in humans such as beriberi (thiamine deficiency), pellagra (nicotinamide deficiency), megaloblastic anaemia (folic acid deficiency), and pernicious anaemia (cobalamin deficiency) (De-Regil 2010; Lassi 2013; Rodríguez-Martín 2001). The therapeutic doses for the various forms of vitamin B complex range widely, from 3 μg/day for vitamin B₁₂ to 18 mg/day for vitamin B₃ in adult males (Chaney 1992; Hillman 1996).

How the intervention might work

The mechanisms by which neuropathic pain develops in diabetes are unclear; mechanisms postulated include alteration in peripheral blood flow, increased vascularity, oxidative stress, and autonomic dysfunction (Edwards 2008; Tesfaye 2011). Overall, there is a paucity of evidence on the role of B vitamins in diabetes. Several studies found lower than normal levels of thiamine in people with diabetes, thought to be due to high renal clearance of thiamine and increased albuminuria in diabetes (Thornalley 2005). Moreover, vitamin B₁₂ deficiency has also been observed in patients with diabetes, partially explained by metformin-induced vitamin B₁₂ deficiency, particularly among people on high doses of metformin (Kibirige 2013). Mecobalamin is a derivative of vitamin B₁₂ involved in processes essential to myelin repair (Sun 2005).

Why it is important to do this review

Untreated DPN is not only associated with a significant cost to the health care system, but has a serious impact on a person's quality of life and general health. If left untreated, serious complications such as loss of function and amputations can occur. To date, evidence on the effectiveness and safety of vitamin B supplements for the treatment of DPN as an additional or alternative option to current treatments have not been fully evaluated. This review will address these issues (Rolim 2009).

Objectives

To assess the effectiveness and safety of vitamin B supplements for the management of pain and nerve damage in people with diabetic peripheral neuropathy.
Methods
Criteria for considering studies for this review

Types of studies

We will include randomised controlled trials (RCTs) and quasi-RCTs (studies that allocate participants to groups by methods that are partially systematic, for example by allocation, case record number or date of birth). We will apply no language limitations. We will include studies completed but not fully reported to reduce the risk of publication bias.

Types of participants

We will include trials of adults, children, or both, with a diagnosis of DPN based on symptoms, abnormal physiological test results, or both. For the purpose of this review, we will use the definitions of diabetes and DPN set by the American Diabetes Association (American Diabetes Association 2014). We will exclude participants with other types of neuropathy. We will exclude people who are vitamin B depleted and taking supplements for replenishment. Participants should not have taken B vitamins in the six months before the start of treatment.

Types of interventions

We will consider trials for inclusion where the intervention is any dose and type of vitamin B supplement (thiamine (B₁), riboflavin (B₂), nicotinic acid (B₃), pyridoxine (B₆), and methylcobalamin, cyanocobalamin, hydroxycobalamin, methylcobalamin, or 5’-deoxyadenosylcobalamin (B₁₂), given by any route, singly or in combination as vitamin B complexes, in comparison to placebo, no treatment, or any comparators for a minimum period of 12 weeks. We will consider trials of vitamin B complexes so long as details of the components are provided.

We will exclude studies using supplements in combination with other vitamins or drugs unless the other vitamins or drugs are administered at the same dose in both intervention and control groups.
Types of outcome measures

Primary outcomes

For painful neuropathy: short-term (three months or less) change in pain intensity, measured as the number of participants with more than a 30% improvement in pain intensity.

For non-painful neuropathy: short-term change in impairment measured by a validated scale, e.g. neuropathy impairment score (NIS) (Dyck 2005).

Secondary outcomes

Long-term (after more than three months) change in pain intensity, measured as the number of participants with more than a 30% improvement in pain.

Long-term (after more than three months) change in impairment measured by a validated scale as for the primary outcome.

3. Change in quality of life measured by a validated scale (e.g. Short-Form 36 Health Survey (SF-36)).

4. Adverse events, reported as all adverse events, adverse events which led to cessation of treatment, and serious adverse events which were life-threatening, fatal, or required or prolonged hospitalisation.
Search methods for identification of studies

Electronic searches

We will identify trials from the Cochrane Neuromuscular Specialized Register, which is maintained by the Information Specialist for the Group. The Information Specialist will search the Cochrane Central Register of Controlled Trials (CENTRAL) (current issue in The Cochrane Library), MEDLINE (January 1966 to current), EMBASE (January 1980 to current), and CINAHL Plus (January 1937 to current). We will adapt the draft MEDLINE strategy in Appendix 1 to search the other databases.

We will also search the US National Institutes of Health Clinical Trials Registry (ClinicalTrials.gov) and the World Health Organization International Clinical Trials Registry Platform (ICTRP) (apps.who.int/trialsearch/). We will search all databases from inception to present.

Searching other resources

We will search reference lists of all primary studies and review articles to identify additional references. We will search relevant manufacturers' websites for trial information. We will search for errata or retractions of included trials.
Data collection and analysis

Selection of studies

Three review authors (HK, CA, and VK) will independently screen titles and abstracts of references from the literature searches and code them as either 'retrieve' (eligible or potentially eligible/unclear) or 'do not retrieve'. We will retrieve the full-text study reports or publications and three review authors (HK, CA and VK) will independently screen the full text and identify studies for inclusion. The review authors will identify and record reasons for exclusion of ineligible studies. We will resolve any disagreement through discussion or, if required, we will consult a third person (HC). We will identify and exclude duplicates and collate multiple reports of the same study so that each study rather than each report is the unit of interest in the review. We will record the selection process in sufficient detail to complete a PRISMA flow diagram and 'Characteristics of excluded studies' table. The review authors will not assess trials in which they are investigators.

Data extraction and management

We will use a data extraction form, which has been piloted on at least one study in the review, for study characteristics and outcome data. Two review authors (VK and HK) will extract study characteristics from included studies.
 We will extract the following study characteristics.

Methods: study design, total duration of study, details of any 'run in' period, number of study centres and location, study setting, withdrawals, and date of study.

Participants: N, mean age, age range, gender, severity of condition, diagnostic criteria, baseline characteristics, inclusion criteria, and exclusion criteria.

Interventions: intervention, comparison, concomitant medications, and excluded medications.

Outcomes: primary and secondary outcomes specified and collected, and time points reported.

Notes: funding for trial, and notable conflicts of interest of trial authors.

Two review authors (CA and HK) will independently extract outcome data from included studies. We will note in the 'Characteristics of included studies' table if the trial report did not provide usable outcome data. We will resolve disagreements by consensus or by involving a third person (VK). One review author (HK) will transfer data into Review Manager (RevMan 2014). A second author will check the outcome data entries. A second review author (CA) will spot-check study characteristics for accuracy against the trial report.
Assessment of risk of bias in included studies

Two review authors (HK and CA) will independently assess risk of bias in each study using the criteria outlined in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). We will resolve any disagreements by discussion or by involving another author (VK). We will assess the risk of bias according to the following domains.

Random sequence generation.

Allocation concealment.

Blinding of participants and personnel.

Blinding of outcome assessment.

Incomplete outcome data.

Selective outcome reporting.

Other bias.

We will grade each potential source of bias as high, low or unclear and provide a quote from the study report together with a justification for our judgment in the 'Risk of bias' table. We will summarise the 'Risk of bias' judgments across the included studies for each of the domains listed. We will consider blinding separately for different key outcomes (e.g. for unblinded outcome assessment, risk of bias for all-cause mortality may be very different than for a patient-reported pain scale). Where information on risk of bias relates to unpublished data or correspondence with a trialist, we will note this in the 'Risk of bias' table.

When considering treatment effects, we will take into account the risk of bias for the studies that contribute to that outcome.
Assesment of bias in conducting the systematic review

We will conduct the review according to this published protocol and report any deviations from it in the 'Differences between protocol and review' section of the Cochrane review.

Measures of treatment effect

We will analyse dichotomous data as risk ratios and continuous data as mean difference, or standardised mean difference for results across studies with outcomes that are conceptually the same but measured in different ways. We will enter data presented as a scale with a consistent direction of effect. We will combine all the data for the outcomes measures provided that the intervention lasted for 12 weeks or more irrespective of the differences in times at which outcomes are calculated between trials.

We will undertake meta-analyses only where this is meaningful, i.e. if the treatments, participants and the underlying clinical question are similar enough for pooling to make sense. We will narratively describe skewed data reported as medians and interquartile ranges.

Unit of analysis issues

The unit of analysis is based on the individual participant (unit to be randomised for interventions to be compared), that is the number of observations in the analysis should match the number of individuals randomised (Higgins 2003).

Where multiple trial arms are reported in a single trial, we will include only the arms relevant to this review. If two or more comparisons (e.g. drug A versus drug B versus placebo) are suitable for inclusion in the same meta-analysis we will combine the relevant intervention groups together or relevant control groups together, or both, as appropriate to create a single pair-wise comparison as recommended in Chapter 16 of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). If this is not possible we will follow alternative methods described in the same chapter.

We will consider only first period data from eligible randomised cross-over studies.

Dealing with missing data

We will report drop-out rates in the 'Characteristics of included studies' table and we will use intention-to-treat analysis (Higgins 2011). We plan to contact trial authors for missing data.

Assessment of heterogeneity

We will consider clinical heterogeneity before making a decision whether to pool studies. We will only perform meta-analysis if participants, interventions and comparisons are sufficiently similar. We will use the I² statistic to measure statistical heterogeneity among the trials in each analysis. If we identify substantial unexplained heterogeneity we will report it and explore possible causes by prespecified subgroup analysis. We will use the following thresholds as a rough guide for interpretation of I², as described in Higgins 2011.

0% to 40%: might not be important.

30% to 60%: may represent moderate heterogeneity.

50% to 90%: may represent substantial heterogeneity.

75% to 100%: considerable heterogeneity.
Assessment of reporting biases

If we are able to pool more than 10 trials, we will create and examine a funnel plot to explore possible small study biases.

Data synthesis

We will use a fixed-effect model in meta-analysis and if heterogeneity is present, compare these results with a those of a random-effects analysis. If the review includes more than one comparison that cannot be included in a single analysis, we will report results for each comparison separately. If the studies have significant heterogeneity and cannot be combined, we will report findings in a narrative form.

We will consider studies of vitamin B complexes as one supplement for the purposes of meta-analysis, taking into account the potential heterogeneity and indirectness of evidence from such analyses when we assess the quality of the evidence.

'Summary of findings' tables

We will create 'Summary of findings' tables using the primary and secondary outcomes. We will use the five GRADE considerations (study limitations, consistency of effect, imprecision, indirectness, and publication bias) to assess the quality of a body of evidence (studies that contribute data for the prespecified outcomes). We will use methods and recommendations described in Section 8.5 and Chapter 12 of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011) using GRADEproGDT software (GRADEpro 2014). We will justify decisions to downgrade or upgrade the quality of the evidence using footnotes and where necessary we will make comments to aid readers' understanding of the review.
Subgroup analysis and investigation of heterogeneity

We plan to carry out the following subgroup analyses.


Types of vitamin B supplement.


Children under 18 and adults.

We will use the primary outcome in subgroup analyses in Review Manager (RevMan 2014).
Sensitivity analysis

We plan to perform the following sensitivity analyses.

Repeat the analysis excluding studies at high risk of bias (from randomisation or blinding of participants).

If there is one or more very large study, repeat the analysis excluding them to determine how much they dominate the results.

Repeat the analysis using a random-effects model if heterogeneity is present.
Reaching conclusions

We will base our conclusions only on findings from the quantitative or narrative synthesis of included studies. Our implications for research will suggest priorities for future research and outline what the remaining uncertainties are in the area.
Acknowledgements

The authors would like to acknowledge the editorial support from Cochrane Neuromuscular and the Information Specialist (Angela Gunn) who developed the search strategy in collaboration with the review authors.

Some sections of the review are based on Ang 2008 and on a protocol template originally developed by Cochrane Airways and adapted by Cochrane Neuromuscular.

This project was supported by the National Institute for Health Research (NIHR) via Cochrane Infrastructure funding to Cochrane Neuromuscular. The views and opinions expressed herein are those of the review authors and do not necessarily reflect those of the Systematic Reviews Programme, NIHR, National Health Service, or the Department of Health. Cochrane Neuromuscular is also supported by the MRC Centre for Neuromuscular Diseases.

Appendices
Appendix 1. DRAFT MEDLINE (OvidSP) search strategy

Database: Ovid MEDLINE(R) <1946 2014="" 4="" october="" to="" week="">
Search Strategy:
--------------------------------------------------------------------------------
1 randomized controlled trial.pt. (397786)
2 controlled clinical trial.pt. (90503)
3 randomized.ab. (293092)
4 placebo.ab. (154196)
5 drug therapy.fs. (1777958)
6 randomly.ab. (205733)
7 trial.ab. (305213)
8 groups.ab. (1307610)
9 or/1-8 (3350308)
10 exp animals/ not humans.sh. (4082107)
11 9 not 10 (2854354)
12 exp Diabetes Mellitus/ (328635)
13 diabet$.mp. (462274)
14 12 or 13 (463642)
15 exp Peripheral Nervous System Diseases/ (119617)
16 15 or (neuropath$ or polyneuropath$).mp. (182081)
17 14 and 16 (20728)
18 Diabetic Neuropathies/ (12459)
19 17 or 18 (20728)
20 exp Vitamin B Complex/tu [Therapeutic Use] (23726)
21 (aminonicotinamide or cobamide$1 or cyanocobalamin or flavin mononucleutide or flavin adenine dinucleotide or fursultiamin or hydroxycobalamin or hydroxocobalamine).mp. (7678)
22 (methylcobalamin or nicorandil or nicotinic acid or nikethamide or pyridoxal or pyridoxamine or pyridoxine or riboflavin or thiamine or vitamin b complex).mp. (54422)
23 or/20-22 (74266)
24 11 and 19 and 23 (203)
25 remove duplicates from 24 (199)
Contributions of authors
HK drafted the protocol. All the other authors provided feedback on it.
Declarations of interest
None known.
Sources of support
Internal sources

None, Other.
External sources

No sources of support supplied

http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD012237/full

VITAMIN D FOR LONGER LIFE

Higher levels of vitamin D may protect people from an earlier death, particularly from cancer and heart disease, suggests a new analysis of existing research.

And, the opposite may also be true — low levels of vitamin D may be linked to a higher risk of premature death.

But the researchers acknowledge that the review’s findings aren’t definitive.

“People with low vitamin D die more frequently from heart disease and cancer, but it is not known if the low vitamin D is a cause of these diseases or just a byproduct of generally poor health,” said study lead author Ben Schoettker, a post-doctoral scientist with the German Cancer Research Center in Heidelberg, Germany.

Still, the research published online June 17 in BMJ does hint at the possibility that vitamin D may benefit people across genders, ages and Western countries, including the United States. The findings are “compellingly consistent,” Schoettker said.

Vitamin D is a hot topic in the medical world. Studies have both supported and debunked its supposed powers as a booster of lifespans. Researchers are looking forward to future studies that they expect to be more definitive.

Vitamin D is nicknamed the sunshine vitamin because the body produces vitamin D when exposed to sunlight. People also get vitamin D through foods like eggs, milk, yogurt, tuna, salmon, cereal and orange juice.

The current analysis only examined what happened to people with various levels of vitamin D in their bodies. The studies included in this analysis didn’t go a step further to randomly assign participants to take vitamin D supplements or an inactive placebo. That kind of study would cost much more, Schoettker said.

The researchers examined eight studies from Europe and the United States that together tracked more than 26,000 nonsmoking men and women. They were all between ages 50 and 79. About 6,700 participants died during the time period of the studies, mostly of heart disease or cancer.

Those with the lowest levels of vitamin D were about 1.5 times more likely than those with the highest levels to die from any cause and from heart disease during the periods of the studies. Those with low levels of vitamin D and a history of cancer were 1.7 times more likely to die of the disease. People who hadn’t previously had cancer saw no change in the risk of cancer death by vitamin D levels.

“Very low vitamin D levels are mainly associated with higher age and lower physical activity,” which could lead to less exposure to the sun, Schoettker noted.

On the other hand, “the reasons for very high vitamin D levels are unknown,” he added.

The researchers pointed out that vitamin D may not change levels of risk for health problems and earlier deaths. It’s possible that levels of vitamin D reflect overall health. Low levels of vitamin D may just be a sign of poor health rather than a cause of it, according to the study.

It’s not clear how vitamin D could help people live longer, but it might have something to do with the way it acts like a hormone, said Susan Mayne, chair of the department of chronic disease epidemiology at Yale School of Public Health. Still, she said, the science linking the vitamin to heart disease and cancer is in its early stages.

For now, both Mayne and Schoettker said people should follow the recommendations of the Institute of Medicine regarding vitamin D. Its 2010 report says most Americans and Canadians already get enough vitamin D. It says nothing about whether people with heart disease or cancer should take supplements, however.

Can Vitamin B Help Neuropathy A Philipino View

Today's post from pchrd.dost.gov.ph (see link below) looks at neuropathy in the Philippines and once again, suggests that Vitamin B complex preparations may help. It has to be pointed out though, that in severe cases, vitamin B combinations may not be enough to control the symptoms and most patients will need to be on some sort of pain reducing medication (see yesterday's post) too. It's always interesting to read views on the disease from all parts of the world.

How Vitamin B can be a remedy for ‘manhid’ and neuropathy
Published on Tuesday, 15 April 2014 08:30 Written by Marge C. Enriquez

Have you ever injured your leg or ankle in a sport and had no sensation or mobility afterward? Hurt your knee then felt prickling sensations even when there was no ligament tear? Slept on an arm and awakened with a numb hand? Sat too long with your legs crossed and ended up with either numbness or a prickling sensation?

This is what many people with peripheral neuropathy experience daily, which is often left unheeded.

Numbness and tingling are just common symptoms of this condition, which involves damage to one or several nerves outside the brain and spinal cord. Effects may include debilitating pain, stinging, swelling, burning, itching, muscle weakness, twitching, loss of sensation (manhid), hypersensitivity to touch (allodynia) and lack of coordination.

Chances are that the disorder afflicts millions of Filipinos and their cases remain unreported.

Disease of the nerves

“Neuropathy is a disease of the nerves,” says Dr. Gio Barangan, medical director of Merck Philippines.

“The major cause in the Philippines is diabetes. When patients are diagnosed with diabetes, there has already been a reduced absorption of vitamins, particularly of B12. Alcoholic patients also suffer from reduced absorption of Vitamin B. Nanginginig sila. (Their joints quiver). In the emergency room, a drunkard with a heart problem is given a high dose of Vitamin B1.”

Neuropathy can also be caused by trauma, injury, putting too much pressure on the nerves or staying in one position too long. If the cause can be corrected through proper nutrition, peripheral nerves can renew slowly and patients can get well.

“The nerve is like electric current and the brain works like Meralco. The speed of delivering the signal from the brain and spinal cord down to the smaller nerves is impaired when there is neuropathy,” says Barangan.

Most doctors recommend Vitamin B complex, which improves nerve functions.

“You need to create a new line of nerves so there won’t be the symptoms. Everyday, your body releases Vitamin B in the body. The moment you lack it, you need to develop it.”

Track record

Merck Philippines has launched a campaign to create awareness about nerve disorders, and how these can be treated with Vitamin B supplements. Research on the Vitamin B market has revealed that many Filipinos complain of prickly sensations, sharp stabbing pains at night or numbness in the arms or legs, yet often ignore the symptoms.

Louie Roxas, Merck’s general manager, said in the past 50 years, Neurobion, a Vitamin B supplement, has been prescribed by doctors to treat this disorder. Because of its track record in safety and efficacy, the company relaunched it as an over-the-counter product.

Neurobion contains Vitamins B1 (thiamine), B6 (pyridoxine) and B12 (cobalamin).

“B1 and B6 will convert the carbohydrates and the food you take into energy. B6 will help synthesize the neurotransmitters. B12 will increase the production of new nerves, in case there is disruption to the synthesis of the nerves,” says Barangan.

Vitamin B12 is vital for the cell function, but a deficit of the vitamin usually appears in nerve cells or in red blood cells.

Asked why B vitamins don’t produce major side effects, Barangan explains: “B1, B6 and B12 are found in food. As vitamins they are water-soluble, thus they have to be replenished every day, unlike Vitamins A, D, E and K which are fat-soluble, meaning they bind to the fats of the body which can invariably be toxic because they are not always expelled. You seldom see toxicity with water-soluble vitamins, which can be excreted in urine and feces.”

He adds that Vitamin B complex shouldn’t just be taken as treatment for a disorder. It should also be consumed as a preventive measure.

“Not all medicines will increase the synthesis of damaged nerves due to trauma. If you take Vitamin B complex daily, the synthesis is faster. It also plays a major role in converting food into energy, and in improving your stamina.”

http://www.pchrd.dost.gov.ph/index.php/2012-05-23-07-46-36/2012-05-24-00-03-06/6693-how-vitamin-b-can-be-a-remedy-for-manhid-and-neuropathy-read-more-http-lifestyle-inquirer-net-157108-how-vitamin-b-can-be-a-remedy-for-manhid-and-neuropathy-ixzz2yuu6cmws-follow-us-inquirerdotnet-on-twitter-inquirerdotnet-on-facebook

Vitamin D And Neuropathy Vid

Today's video is from Dr. John Hayes Jr, who is rapidly establishing himself as one of the best neuropathy information givers on the net. Today he talks about the value of Vitamin D in relation to neuropathy.



Episode 14 – Vitamin D
Thursday, June 13th, 2013 Posted by John Hayes Jr

Dr. Hayes talks about Vitamin D, why it’s important for Neuropathy patients, potential sources, and the consequences of both deficiency and overdose.



http://beatingneuropathy.tv/2013/06/episode-14/

Vitamin B3 Niacin For Neuropathy Vid

Today's short video is another one from beatingneuropathy.tv (see link below) and is part of a very helpful series made by Dr. John Hayes Jr, who has appeared on this blog quite a few times. It talks about Vitamin B3 being important for neuropathy and chronic pain patients and why.

Episode 17 – Niacin
Posted by John Hayes Jr Thursday, July 11th, 2013

Dr. Hayes discusses niacin, why it’s important for neuropathy and chronic pain patients, deficiency symptoms, and starting a supplementation regimen with your healthcare professional.

http://beatingneuropathy.tv/2013/07/episode-17/

VITAMIN E SUPPLEMENTS DONT HELP CATARACT

Taking daily supplements of selenium and/or vitamin E appears to have no significant effect on the development of age-related cataracts in men, writes Author William G. Christen, Sc.D., of Brigham & Women's Hospital and Harvard Medical School, Boston, and colleagues

Some research, including animal studies, has suggested that dietary nutrients can have an effect on the onset and progression of cataracts. Vitamin E and selenium are of particular interest.

The authors report the findings for cataracts from the Selenium and Vitamin E Cancer Prevention Trial (SELECT) Eye Endpoints (SEE) Study. The SEE study was an ancillary study of SELECT, a randomized placebo-controlled trial of selenium, vitamin E and a combination of the two in prostate cancer prevention among 35,533 men (50 years and older for black men and 55 years and older for all other men). Men were asked to report cataract diagnosis or removal since entering the SELECT trial. A total of 11,267 SELECT participants took part in the SEE study.

During an average of 5.6 years of treatment and follow-up, there were 389 cases of cataracts. There were 185 cases of cataracts in the selenium group and 204 in the group that didn't take selenium. There were 197 cases of cataracts in the vitamin E group and 192 in the group without vitamin E. Results were similar for cataract removal.

"These randomized trial data from a large cohort of apparently healthy men indicate that long-term daily supplemental use of vitamin E has no material impact on cataract incidence. The data also exclude any large beneficial effect on cataract for long-term supplemental use of selenium, with or without vitamin E, although a smaller but potentially important beneficial effect could not be ruled out."