Tuesday, 17 January 2017

An Honest Reflection Of The Current State Of Neuropathy Treatment

Today's post from medscape.com (see link below) may depress the hell out of you because it's basically an analysis of the failures with neuropathy treatment and diagnostic testing over the last decades. At least Medscape are honest here and don't try to pull the wool over our eyes with promises of exciting new developments in the field of nerve damage control. There are exciting new developments and this blog highlights them when they emerge but as the co-author rightly states: "As a clinician, I'm frustrated that current drugs have no benefit for the underlying nerve damage. We have witnessed failure after failure of clinical trials of disease-modifying drugs, because the end points are not fit for that purpose." Says it all really! That said, as patients, we have to remain optimistic and we have to report individual failures as they happen, so that enough evidence can be built up to confirm or reject any particular drug's effectiveness. We also need to continue to explore options from the alternative circuits. All we're interested in really is reducing our daily discomfort and it has to be said, progress in that area has largely been patient-led during the last decades because standard drug treatments are pretty much the same as they've been for decades and they are largely ineffective. This blog does take issue with the recommendation of Pregabalin as a first-line treatment but apart from that, the article presents a scenario that we can all recognise and reflects our frustrations as patients too.
 
New ADA Guidance Charts Success, Failure in Diabetic Neuropathy
Miriam E Tucker January 09, 2017

Notably missing from the first US guidelines to address diabetic neuropathy in more than a decade is any recommendation for disease-modifying treatments, since none are currently approved by the US Food and Drug Administration (FDA).

Indeed, many candidate drugs for diabetic neuropathy have failed in trials, and one of the new guideline authors believes novel end points — particularly measures of small-nerve fiber damage and repair — that could better assess a potential drug's efficacy need to be employed in clinical studies.

Coauthor Rayaz A Malik, MBChB, FRCP, PhD, of Weill Cornell Medicine-Qatar, Doha and New York, told Medscape Medical News, "As a clinician, I'm frustrated that current drugs have no benefit for the underlying nerve damage. We have witnessed failure after failure of clinical trials of disease-modifying drugs, because the end points are not fit for that purpose."

Such assessments of small-nerve fiber damage should also be used for earlier diagnosis of diabetic neuropathy, says Dr Malik.

"Although about 20% of patients have painful neuropathy and can present to their doctor, the majority have painless neuropathy, which is silent and is diagnosed only when it is too late and the patient has already developed a foot ulcer," he continued.

"Given that the 5-year mortality of a patient with a foot ulcer is worse than most cancers, there is a need to identify early neuropathy. Yet currently advocated tests, like the monofilament, identify only patients with advanced neuropathy. Why do we have robust methods for detecting early retinopathy and nephropathy, but not neuropathy?"

Published in the January issue of Diabetes Care, the new ADA position statement revises ADA's last neuropathy guideline, published in 2004.

The new document covers prevention and management of distal symmetric polyneuropathy (DSPN), diabetic autonomic neuropathies including cardiovascular autonomic neuropathy (CAN), as well as less common forms of neuropathy.

The aim is to provide state-of-the-art information for clinical management of the condition but to also acknowledge the current lack of disease-modifying drugs.

Most Patients Don't Need Sophisticated Testing or Opioids


Lead author of the new guidelines, Rodica Pop-Busui, MD, PhD, of the University of Michigan, Ann Arbor, told Medscape Medical News that there are two key clinical messages in the new document: the first is that electrophysiologic testing or referral to a neurologist is rarely needed for diagnosing neuropathy and the second is that opioids for the pain of diabetic neuropathy should be considered only as a very last resort and not as first- or second-line therapy,

"The purpose of the document is to provide clinicians with evidence-based tools to understand how to diagnose, monitor, and manage some of the aspects related to diabetic neuropathy.…It provides a tool to help them confidently diagnose neuropathy on their own and avoid expensive unnecessary tests or referrals," Dr Pop-Busui said.

The statement also covers neuropathy prevention, including glycemic control and lifestyle modification. Assessment for DSPN, the document advises, should be undertaken at diagnosis of type 2 diabetes, 5 years after diagnosis of type 1 diabetes, in those with prediabetes and symptoms of peripheral neuropathy, and every year thereafter.

Modalities for assessment should include careful history and either temperature or pinprick sensation to assess small-fiber function, along with tuning fork for vibration sensation, and 10-g monofilament testing for ulceration risk.

Electrophysiologic testing or referral to a neurologist is rarely necessary, except in atypical situations."There were several neurologists on the writing group, in addition to endocrinologists. We reached the same conclusion — that referral is not needed for typical cases of diabetic neuropathy — and we have provided a stepwise approach to get an idea of whether a patient has typical symptoms and signs," Dr Pop-Busui noted.

For treating neuropathic pain, the document advises the FDA-approved pregabalin or duloxetine as first-line treatment and various nonapproved agents, including gabapentin or tricyclic antidepressants, as second-line. Due to the high risks of addiction and other complications, opioids are advised only for patients with severe pain who don't respond to other medications, and referral to specialized pain clinics is advised in such cases.

Recommendations are also provided for assessment of cardiovascular, gastrointestinal, and urogenital autonomic neuropathies in patients with microvascular and neuropathic complications.

Included are considerations for excluding other conditions or drug effects that could be mimicking the symptoms, use of short-term metoclopramide for treatment of gastroparesis, assessment of patient-specific neuropathy-related end points, such as falls and mobility, and assessment of less common neuropathies.

"Hopefully readers will find this document very useful. We tried to make it very easy to read, with pearls that are all evidence-based.…We want to give them the tools to be able to see a complicated patient with diabetic neuropathy relatively easily in their office," Dr Pop-Busui explained.

Why Aren't There Any Drugs to Treat Neuropathy?

In the document's final section "Neuropathy Clinical End Points for Research and Clinical Trials," the authors point out that "multiple clinical trials for these conditions have failed."

They cite as contributing factors "a lack of agreement and uniformity in the use of the most sensitive DSPN measures that capture the natural history of the disease and detect repair in the specific nerve-fiber populations, as well as the inclusion of appropriate patient populations."

For DSPN drug trials in particular, the statement recommends the use of validated clinical instruments for assessing symptoms and disability, along with advice to "consider" using electrophysiology and measures of small-fiber damage and repair, such as intraepidermal nerve-fiber density or corneal confocal microscopy.

Dr Malik has long maintained that one of the main impediments to better neuropathy treatment in both clinical practice and research has been the focus on measures of symptoms and large-fiber dysfunction, rather than assessment of small-fiber damage and repair that occurs earlier and could therefore serve as a more appropriate target for early intervention and for the development of drugs to treat neuropathy.

"I honestly believe there are many drugs that have failed because of this. If you test small fibers they repair sooner than large fibers. If you do a clinical trial lasting only 1 or 2 years you actually might not see the benefit of that drug because you're not looking at the small fibers….Big Pharma has invested huge amounts of money in disease-modifying drugs, but they've all failed," Dr Malik asserted.

He blames advisors to the FDA for not "moving away from symptoms, signs, and neurophysiology" and for not allowing small-fiber assessment to be at least a secondary end point in drug trials "to give disease-modifying therapies a fighting chance."

He believes that many promising drugs like the aldose reductase inhibitors, nerve growth factor, C-peptide, and the novel investigational peptide ARA 290 (Araim Pharmaceuticals) could well be approved for DSPN if small-fiber evaluation were included as an end point.

However, Dr Pop-Busui pointed out, other candidate drugs have failed due to toxicity — notably the aldose-reductase inhibitors — although one of those (epalrestat) is currently licensed for DSPN in some countries in Asia.

Also, she noted that there has been difficulty in identifying an appropriate animal model for human diabetic neuropathy.

"We are working very hard to try to identify the right targets that can be developed into more successful phase 2 and phase 3 trials....This is a very complex question," she said.

What's the Best Tool for Research and Clinical Practice?

Dr Malik has conducted extensive research demonstrating the utility of corneal confocal microscopy, a tool originating from ophthalmology that has been shown to predict the development of peripheral neuropathy in patients with diabetes and even prediabetes.

Corneal confocal microscopy could serve both clinically and as a surrogate end point in clinical trials as a noninvasive alternative to skin biopsy for the assessment of early small-fiber damage and repair. This is the type of tool needed for drug development, he believes.

"No drug company is going to invest in a 5-year clinical trial. What you need is something that will give you a signal that nerves are beginning to repair within 12 months, which then allows you to continue and show that other tests like [quantitative sensory testing] and neurophysiology also improve," he explained.

"The monofilament and neurological examination are very good at picking up advanced neuropathy and identifying the high-risk foot but are terrible at detecting early neuropathy and indeed nerve repair," he added.

But such tools still play an important role in clinical practice, Dr Pop-Busui stressed.

"Some tools may be ancient but in fact provide extremely important information. These tools can be carried in a physician's pocket and used in a few minutes. Yes, we are using technology in many aspects of diabetes management, but in diabetic neuropathy, the clinical exam is very important."

And she pointed out that use of tools such as corneal confocal microscopy at this point is unlikely to change clinical practice.

"We don't have preventive treatments, so we wouldn't do anything different. We would still treat their glucose and other risk factors. We don't have other pathogenic treatments as we talk right now."

For the current document, she said, "The task given to us was to help physicians and patients to have the best effective care of the complication with all the information critically evaluated. In medicine things change all the time. If the evidence changes, we will update the document."

FDA Still Working on Development Programs for Agents for DSPN

Both Drs Pop-Busui and Malik participated in a February 2013 FDA public workshop, "Clinical Development Programs for Disease-Modifying Agents for Peripheral Neuropathy."

In response to a Medscape Medical News query about the outcome of that meeting and the status of the end-points issue, an FDA spokeswoman responded: "The FDA has taken into account the information discussed at the 2013 public workshop and the comments received as we continue to work with industry on clinical development programs for disease-modifying products for the management of peripheral neuropathy. We will provide updates on this topic as appropriate."

The guidelines authors have no relevant financial relationships.

For more diabetes and endocrinology news, follow us on Twitter and on Facebook.

Diabetes Care. 2017;40:136-154. Article

http://www.medscape.com/viewarticle/874162

Monday, 16 January 2017

Neuropathy Treatment Alternatives With Video Explanations (Vid)

Today's post from aboutperipheralneuropathy.blogspot.com (see link below) is useful for many neuropathy patients searching for alternative treatments after almost all else has failed. The difference with other similar posts here on the blog is that it uses videos to illustrate the information given and these automatically lead to a better understanding compared with a black and white text. That is not to say that everything you see here is 100 % true, or will certainly work. That depends on the user and it would be advisable to do much more research of your own into each of these treatments and maybe discuss it with your doctor before beginning. St. John's Wort for instance, is a definite no-no for people under treatment for HIV because it interferes with the workings of the HIV drugs. Therefore, doing your own background investigations is very important. However, the information you see here is extremely useful, if only to convince you that a particular treatment is not for you. Cost is also an issue for many people whose insurance doesn't cover such alternative therapies. Nevertheless, worth a read.

Alternative Treatments for Peripheral Neuropathy

Posted 1 week ago by Srikanth R  Jan 1 2017
 
Peripheral means beyond, here, beyond the brain and the spinal cord. Neuro means related to nerves. Pathy is a suffix derived from the Greek term pathos, which means suffering or disease.



Peripheral neuropathy is a disorder that occurs when the peripheral nerves do not function properly due to damage.

Here are some alternative treatments for peripheral neuropathy.

Yoga

Yogasanas like Pawanamukthasana and Adho Mukha Shwanasana are helping many peripheral neuropathy patients mamage the disease.



Herbs


St. John's Wort alleviates pain. Capsaicin is an anti-inflammatory substance found in chili peppers. Topical creams containing this substance reduce burning sensation.





L-Carnitine

Human body produces L-carnitine and stores it in organs like brain and liver. Diabetics who display neuropathy symptoms may regain regular sensation in their limbs by increasing L-carnitine levels in the body. This is as per experts at the University of Maryland Medical Center



 

Vitamins

Peripheral neuropathy may also be caused by deficiency in vitamins B1, B12 and E. In these cases consuming foods containing these vitamins may reduce symptoms.







Acids

Omega-3 fatty acids and essential fatty acids called gamma linolenic acid (GLA) and alpha-Lipoic acid (ALA) help diabetic peripheral neuropathy patients. This is as per Kathleen Head's statistics in the Alternative Medicine Review. These acids improve blood flow and reduce peripheral neuropathy symptoms. 



Acupuncture

Acupuncture, a key component of traditional Chinese medicine (TCM), eases pain caused by nerve damage. 




Tai Chi

Li Li, a professor of kinesiology at LSU, uses Tai Chi to fight peripheral neuropathy.


Alternative treatments are benefitting many peripheral neuropathy patients worldwide.

http://aboutperipheralneuropathy.blogspot.com/2017/01/alternative-treatments-for-peripheral_1.html

Sunday, 15 January 2017

The Return Of The Red Hot Chili Peppers For Nerve Pain: Worth The Effort?

Today's post from onlinelibrary.wiley.com (see link below) should make us thankful that organisations such as the Cochrane pain, palliative and supportive care group are prepared to examine many aspects of neuropathy treatment objectively and present their results for all to see. It's been a long time coming but adds an invaluable resource to all the information that neuropathy patients need. In this case, the subject is capsaicin (derived from chili peppers) which has had its moments in the neuropathy headlines over the years but always seems to recede into the background as newer treatments are found. This has largely been because doctors are not sure what to prescribe, or how effective it will be: whether it's low-strength creams, or high-concentrate patches and generally leave it up to the patients as to decide if it works or not. Another problem is the aggressive nature of capsaicin itself. Depending on how you apply it and for how long, you can easily burn yourself to such an extent, that the ensuing pain is worse than the nerve pain itself. This article comes to the conclusion that despite the difficulties and care needed with application, high strength capsaicin patches can help certain groups of nerve pain patients but actually, in general, there's very little evidence that it can help on a wider scale. An interesting post, worth a read, especially if you have tried capsaicin in the past, or are considering trying it in the future. Whatever you do, don't use this stuff without careful discussion with your doctor - the folk tales about chili peppers are true!



Topical capsaicin (high concentration) for chronic neuropathic pain in adults
Authors Sheena Derry, Andrew SC Rice, Peter Cole, Toni Tan, R Andrew Moore First published: 13 January 2017
Editorial Group: Cochrane Pain, Palliative and Supportive Care Group
DOI: 10.1002/14651858.CD007393.pub4


Abstract
Background


This review is an update of 'Topical capsaicin (high concentration) for chronic neuropathic pain in adults' last updated in Issue 2, 2013. Topical creams with capsaicin are used to treat peripheral neuropathic pain. Following application to the skin, capsaicin causes enhanced sensitivity, followed by a period with reduced sensitivity and, after repeated applications, persistent desensitisation. High-concentration (8%) capsaicin patches were developed to increase the amount of capsaicin delivered; rapid delivery was thought to improve tolerability because cutaneous nociceptors are 'defunctionalised' quickly. The single application avoids noncompliance. Only the 8% patch formulation of capsaicin is available, with a capsaicin concentration about 100 times greater than conventional creams. High-concentration topical capsaicin is given as a single patch application to the affected part. It must be applied under highly controlled conditions, often following local anaesthetic, due to the initial intense burning sensation it causes. The benefits are expected to last for about 12 weeks, when another application might be made.
Objectives

To review the evidence from controlled trials on the efficacy and tolerability of topically applied, high-concentration (8%) capsaicin in chronic neuropathic pain in adults.
Search methods

For this update, we searched CENTRAL, MEDLINE, Embase, two clinical trials registries, and a pharmaceutical company's website to 10 June 2016.
Selection criteria

Randomised, double-blind, placebo-controlled studies of at least 6 weeks' duration, using high-concentration (5% or more) topical capsaicin to treat neuropathic pain.
Data collection and analysis

Two review authors independently searched for studies, extracted efficacy and adverse event data, and examined issues of study quality and potential bias. Where pooled analysis was possible, we used dichotomous data to calculate risk ratio and numbers needed to treat for one additional event, using standard methods.

Efficacy outcomes reflecting long-duration pain relief after a single drug application were from the Patient Global Impression of Change (PGIC) at specific points, usually 8 and 12 weeks. We also assessed average pain scores over weeks 2 to 8 and 2 to 12 and the number of participants with pain intensity reduction of at least 30% or at least 50% over baseline, and information on adverse events and withdrawals.

We assessed the quality of the evidence using GRADE and created a 'Summary of findings' table.


Main results

We included eight studies, involving 2488 participants, two more studies and 415 more participants than the previous version of this review. Studies were of generally good methodological quality; we judged only one study at high risk of bias, due to small size. Two studies used a placebo control and six used 0.04% topical capsaicin as an 'active' placebo to help maintain blinding. Efficacy outcomes were inconsistently reported, resulting in analyses for most outcomes being based on less than complete data.

For postherpetic neuralgia, we found four studies (1272 participants). At both 8 and 12 weeks about 10% more participants reported themselves much or very much improved with high-concentration capsaicin than with 'active' placebo, with point estimates of numbers needed to treat for an additional beneficial outcome (NNTs) of 8.8 (95% confidence interval (CI) 5.3 to 26) with high-concentration capsaicin and 7.0 (95% CI 4.6 to 15) with 'active' placebo (2 studies, 571 participants; moderate quality evidence). More participants (about 10%) had average 2 to 8-week and 2 to 12-week pain intensity reductions over baseline of at least 30% and at least 50% with capsaicin than control, with NNT values between 10 and 12 (2 to 4 studies, 571 to 1272 participants; very low quality evidence).

For painful HIV-neuropathy, we found two studies (801 participants). One study reported the proportion of participants who were much or very much improved at 12 weeks (27% with high-concentration capsaicin and 10% with 'active' placebo). For both studies, more participants (about 10%) had average 2 to 12-week pain intensity reductions over baseline of at least 30% with capsaicin than control, with an NNT of 11 (very low quality evidence).

For peripheral diabetic neuropathy, we found one study (369 participants). It reported about 10% more participants who were much or very much improved at 8 and 12 weeks. One small study of 46 participants with persistent pain following inguinal herniorrhaphy did not show a difference between capsaicin and placebo for pain reduction (very low quality evidence).

We downgraded the quality of the evidence for efficacy outcomes by one to three levels due to sparse data, imprecision, possible effects of imputation methods, and susceptibility to publication bias.

Local adverse events were common, but not consistently reported. Serious adverse events were no more common with active treatment (3.5%) than control (3.2%). Adverse event withdrawals did not differ between groups, but lack of efficacy withdrawals were somewhat more common with control than active treatment, based on small numbers of events (six to eight studies, 21 to 67 events; moderate quality evidence, downgraded due to few events). No deaths were judged to be related to study medication.
Authors' conclusions

High-concentration topical capsaicin used to treat postherpetic neuralgia, HIV-neuropathy, and painful diabetic neuropathy generated more participants with moderate or substantial levels of pain relief than control treatment using a much lower concentration of capsaicin. These results should be interpreted with caution as the quality of the evidence was moderate or very low. The additional proportion who benefited over control was not large, but for those who did obtain high levels of pain relief, there were usually additional improvements in sleep, fatigue, depression, and quality of life. High-concentration topical capsaicin is similar in its effects to other therapies for chronic pain.

Plain language summary

Capsaicin applied to the skin for chronic neuropathic pain in adults

Bottom line

There is moderate quality evidence that high-concentration (8%) capsaicin patches can give moderate pain relief, or better, to a minority of people with postherpetic neuralgia, and very low quality evidence that it benefits those with HIV-neuropathy and peripheral diabetic neuropathy.

Background

Neuropathic pain is caused by damage to nerves, either from injury or disease. Pain is described as chronic if it has been experienced on most days for at least three months. Capsaicin is what makes chilli peppers hot. It is thought to reduce chronic neuropathic pain by making nerves insensitive to pain messages. This review is an update of one last published in 2013, and is about a highly concentrated preparation of capsaicin (8%) that must be administered in carefully controlled conditions in a clinic or hospital, often following local anaesthetic, because without special precautions it can initially cause pain a feeling of burning on the skin. It is used only to treat localised areas of pain. The single application is designed to produce relief of pain for up to three months.

Study characteristics

We searched scientific databases for studies that looked at the effects of high-concentration capsaicin in adults who had moderate or severe neuropathic pain. The treatment had to have effects measured for at least 8 weeks. The evidence is current to June 2016.

Eight studies satisfied our inclusion criteria, including two new studies for this update. The studies were well conducted.

Key results

In seven studies, involving 2442 participants, we found that the treatment gave good levels of pain relief to a small number of participants with some types of neuropathic pain (pain after shingles, and nerve injury pain associated with HIV infection), and probably also in another type (painful feet because of damaged nerves caused by diabetes). About 4 in 10 people had at least moderate pain relief with capsaicin compared with 3 in 10 with control. The control was a treatment that looked the same but did not contain high levels of capsaicin, with either nothing added, or very small amounts of capsaicin added. In one small study (46 participants) in people with persistent pain after hernia surgery, it did not seem better than control.

In all people who have this treatment there can be short-lived localised skin problems such as redness, burning, or pain. Serious problems seem to be uncommon, and were no more frequent in these trials with high-concentration capsaicin than with control using very low-concentration capsaicin or placebo.

Slightly more people treated with control rather than capsaicin dropped out of the studies because of lack of benefit, but there was no difference between the groups for drop-outs because of side effects.

Quality of the evidence

We judged the quality of the evidence as moderate or very low for pain relief outcomes, mainly because only a small number of studies and moderate number of participants provided information for each outcome. We judged the quality of the evidence as moderate for harmful effects. Moderate quality means that further research may change the result. Very low quality means we are very uncertain about the results.

http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD007393.pub4/full

Saturday, 14 January 2017

Should Neuropathy Patients Supplement With Vitamin B12?

Today's post from draxe.com (see link below) is a valuable follow up to yesterday's post about a study into vitamin B supplementation. It looks at vitamin B12 in particular and contains lots of useful information that you really need to read before supplementing for yourself. The most important thread running through the article is that you need to know if you have a B12 deficiency first before starting a course of B12 supplements, or B12 injections and the only person who can tell you this is your doctor. Many so-called 'miracle cures' for neuropathy are based on high vitamin B12 supplementation but you surely know by now which fantasy claims to ignore and of course, anything that has the word 'cure' in the title, is just cruel profiteering because as you know, nerve damage can't be cured, only the symptoms can be treated and hopefully reduced. This is why advertisers use the words 'vitamin B12' as a sort of trigger to fool the customer into thinking 'it must be good then'! Nevertheless, there's enough evidence to prove the benefits of B12 under the right conditions and the first of these conditions is having a B12 deficiency. Maybe time to arrange some tests with your doctor before heading for the health food store or buying on internet. This article will provide you with some good background information.

 
Vitamin B12 Injections Benefits, Risks and Better Alternatives? 

Dr Josh Axe 2016



Vitamin B12 deficiency is believed to be one of the most common nutrient deficiencies in the world, especially among people taking stomach acid-altering medications and antibiotics frequently, along with the elderly and sometimes vegetarians/vegans. (1) For this reason, B12 injections are sometimes used to offset the many symptoms of vitamin B12 deficiency, such as fatigue and weakness, poor moods, and low concentration.

Even more serious is that B12 deficiency can disturb red blood cell formation and elevate homocysteine levels, which negatively impacts neurological and cardiovascular health, in addition to posing risks during pregnancy.

While foods like grass-fed beef, dairy products and fish supply a good dose of vitamin B12, some people abstain from eating these foods or have a harder time absorbing and actually utilizing this nutrient due to digestive/metabolic limitations. Sometimes certain genetic conditions can hinder the body’s use of vitamin b12, and other times low dietary intake plus unhealthy lifestyle habits are to blame. Plus, because b12 vitamin is bound to amino acids (found in protein foods) and is only released when certain enzymes and stomach acids are present, it’s possible to consume enough but still remain somewhat deficient.

So are B12 injections the answer to restoring health in those with low levels? Vitamin B12 benefits and benefits of receiving B12 injections can include improved moods, protection against cognitive decline and better energy, but as you’ll learn, there are also risks involved. Secondly, B12 shots don’t always resolve the underlying problem of deficiency, so they’re not the be-all and end-all when it comes to treating symptoms.
What Are B12 Injections?

B12 injections are shots that contain high doses of vitamin B12, used to quickly elevate levels in someone with a deficiency.

What does vitamin B12 do exactly?

Vitamin B12 is an essential vitamin that’s crucial for many vital metabolic and hormonal functions — including the production of digestive enzymes and carrying important nutrients into and out of cells. Due to how it helps convert and synthesize many other compounds within the body, it’s needed for well over 100 daily functions. Some of the roles that are attributed to vitamin B12 include:
Forming red blood cells
Playing a role in DNA/RNA synthesis
Acting as a cofactor for methionine synthase (helping with methylation or the conversion of homocysteine to methionine, which protects cardiovascular health and more)
Facilitating metabolic conversion of protein and fats
Carrying out neurotransmitter functions and helping with production of hormones
Helping convert amino acids and make creatine
Producing myelin sheath (the coating of nerves)
Helping with synthesis of hemoglobin
Playing a role in fetal development during pregnancy

Vitamin B12 levels are usually tested with a blood serum test, and values below approximately 170–250 picogram per milliliter in adults are considered signs of deficiencies. However, it’s common for blood tests to reveal inaccurate information regarding B12 levels since a high percentage is stored in the liver and not always revealed through testing (for example, taking large amounts of folic acid has been found to mask vitamin B12 deficiency in some patients). (2)

Vitamin B12 shots are normally available by prescription only and are administered into a patient’s muscle tissue about once monthly, although dosage varies depending on age and medical history.

Studies show that most people living in industrialized nations tend to get enough vitamin B12, although not all. (3) Vitamin B12 shots are administered most often in those with genetic conditions that block absorption and people with the disorder called pernicious anemia, which can result in severe malabsorption and deficiency. Pernicious anemia is caused by a decrease in red blood cells when the body can’t absorb enough vitamin B12, greatly raising the risk for neurological complications.

According to the National Institute of Health, the two forms of vitamin B12 that are “active” within the human body are called methylcobalamin and 5-deoxyadenosylcobalamin. Because vitamin B12 contains the mineral cobalt, various compounds within vitamin B12 activity are sometimes referred to as “cobalamins.” Vitamin B12 supplements usually contain the type called cyanocobalamin, which easily converts to the vitamin’s active forms (although this doesn’t always mean that absorption is high). (4) The absorption of vitamin B12 requires something called intrinsic factor, which is found in stomach acid.
B12 Injection Potential Benefits vs. Risks

The NIH reports that in those with confirmed deficiency, B12 injections can have important benefits. However, it’s been found that oral B12 supplementation when taken in high doses can have similar protective effects. For example, one study found that taking 1,000–2,000 micrograms orally in properly timed doses helped improve levels as much as injections. (5, 6)
Benefits of B12 Injections:
Might Reduce Depression, Cognitive Decline and Dementia: Some studies show that, especially in older people, supplementing with vitamin B12 can prevent depression, restore better mood control and retain healthy memory/mental functioning. (7)
Helps Lower Fatigue: Restoring vitamin B12 to healthy levels can treat anemia, help with conversion of macronutrients and production of creatine (beneficial for building muscle mass), and reduce muscle weakness.
Can Help Improve Your Metabolism: Some people turn to vitamin B12 shots to overcome a sluggish metabolism and even help with weight loss. Because injections might give patients more energy and regulate hormone production, it’s possible to experience changes in appetite, improved sleep and better exercise performance. Some even claim B12 shots improve appearance of their skin, hair and nails.
Protects the Heart: Elevated homocysteine levels have been identified as a risk factor for cardiovascular disease, the No. 1 killer of adults in industrialized nations. Vitamin B12 is needed for conversion of homocysteine and therefore can prevent conditions or complications like heart attack, stroke or coronary heart disease.
Improves Low Sperm Count
Helps with Fetal Development During Pregnancy (8)
Helps Prevent or Treat Diabetic Neuropathy




Risks/Drawbacks of B12 Injections:

 
Problems with Absorption: Even if someone receives high doses of vitamin B12, it doesn’t necessarily mean that his or her body has the ability to properly absorb and use the whole dose. That’s because utilization of vitamin B12 (especially from supplements) depends on levels of other metabolic cofactors and acids. The NIH reports that only about 10 micrograms of a 500-microgram oral supplement is actually absorbed in healthy people due to limitations of stomach acid and intrinsic factor.
Interactions with Medications: Vitamin B12 has the potential to interact with certain medications, including diabetic prescriptions, metformin, proton pump inhibitors, antagonists and antibiotics. High doses might also possibly interfere with levels of other vitamins, enzymes and minerals, which is always a potential problem when taking any nutrient in very large quantities.

Wondering if it’s dangerous to take too much vitamin B12?

Because it’s a water-soluble vitamin, any excess that isn’t used should be flushed from the body and not pose too much risk (not the case with fat-soluble vitamins like vitamin A). The Institute of Medicine reports that “no adverse effects have been associated with excess vitamin B12 intake from food and supplements in healthy individuals.” (9)

However, if you’re not deficient in vitamin B12 to begin with or you don’t address the underlying reasons you might be deficient, injections likely won’t do much to improve overall quality of life. As researchers from Cornell University Medicine put it, “Management requires correctly diagnosing cobalamin deficiency, reversing it, defining its underlying causes, preventing relapse, managing the underlying disorder and its complications, and educating the patient.” (10)
How to Know You’re Low in B12: Signs and Symptoms of B12 Deficiency

Signs and symptoms that you might be suffering from B12 deficiency can include: (11)
chronic fatigue, lethargy and weakness
Muscle aches, joint pain and trouble exercising
Poor memory, inability to concentrate and other cognitive problems associated with aging
Mood changes, like increased depression and anxiety, or signs of nervousness like rapid heartbeats/palpitations
Poor dental health, including bleeding gums and mouth sores
Shortness of breath and feeling dizzy
Poor appetite or digestive problems like constipation, nausea, diarrhea or cramping
Sometimes greater risk for problems like cardiovascular complications or even cancer (due to a rise in homocysteine levels)

Why might you be low in vitamin B12, even if you eat a relatively healthy diet? One reason is being low in a type of compound produced within the stomach called intrinsic factor (a type of glycoprotein), which combines with vitamin B12 once consumed in order to allow it to be absorbed. Research shows that around 50 percent to 60 percent of ingested vitamin B12 is usually absorbed when enough intrinsic factor is present in relation to B12, but absorption decreases drastically when this ratio changes.

Older people usually produce less stomach acid and therefore less intrinsic factor, increasing their risk for deficiency. People who take medications regularly that decrease stomach acid production can also become deficient in vitamin B12 for this reason, whether they consume enough from their diets or not.

Because of how vitamin B12 is absorbed, the most common risk factors for B12 deficiency are:
Genetic susceptibility: Some people genetically produce less intrinsic factor and stomach acid needed for B12 absorption. This population might benefit most from injections if dietary improvements don’t do enough to raise levels.
Having an autoimmune disease: Some autoimmune diseases can damage the stomach lining (including pernicious anemia) where intrinsic factor is produced.
Older age: Due to changes in dietary nutrient intake (usually from eating less overall) and also decreased production of stomach acid, the elderly tend to have reduced levels of vitamin B12. This is one reason that mood changes, poor memory and weakness become more common with older age.
Having an intestinal disorder resulting in less stomach acid: These include conditions like gastritis, hypochlorhydria or achlorhydria. Problems can also arise after intestinal or stomach surgeries are performed. (12)
Taking stomach acid-lowering drugs: Medications can block absorption, including antacids used to treat conditions like gastritis or esophageal reflux and antihistamines.
Being a vegetarian or vegan: This group consumes less foods that are naturally high in vitamin B12, such as beef and poultry (and sometimes dairy and fish too), which means their intake of vitamin B12 is lower whether their absorption is adequate or not.
Better Ways to Address B12 Deficiency

The ideal and safest way to consume enough of any nutrient is getting it naturally through whole food sources. However, sometimes due to other health conditions or food preferences, this isn’t always possible. But if you can, you should consume foods that provide this valuable vitamin.

The foods highest in vitamin B12 are:
Organ meats, such as beef and chicken liver
Wild-caught fish, including salmon, herring, mackerel, tuna, trout and sardines (also great sources of other vital nutrients like omega-3 fatty acids)
Organic dairy products, including probiotic-rich yogurt or raw milk
Pasture-raised poultry, including turkey or chicken
Grass-fed beef and lamb





When it’s not possible to get enough vitamin B12 from your diet, perhaps due to genetic conditions or taking necessary medications, someone might choose to boost intake of vitamin B12 in several ways other than receiving injections. These can include taking oral dietary supplements and now even a new form of prescription vitamin B12 medication available in gel form. Studies show these seem to work in similar ways to improve symptoms.

Gel formulations of vitamin B12 are somewhat new and applied into the nostrils (intranasally). They’re now considered an alternative to vitamin B12 injections that some prefer because they require no needles. There is not as much evidence regarding long-term efficacy or safety of gel vitamin B12 compared to injections, but at this time it appears B12 gel works similarly to raise blood levels. Remember that whether you choose to use vitaminBb12 in supplement form or not to resolve deficiency symptoms, it’s important to identify the real reason you’re struggling with deficiency in the first place.


Final Thoughts on Vitamin B12 Injections

 
Vitamin B12 injections (or shots) are used to overcome vitamin B12 deficiency, which is common especially among the elderly, those with intestinal damage or disorders, people with pernicious anemia, and vegetarians/vegans.
The benefits of vitamin B12 injections include treating or preventing symptoms, such as fatigue, heart problems, neurological damage, mood changes, muscle weakness and hormone imbalances.
The best way to get enough vitamin B12 is through a healthy diet whenever possible, such as from consuming grass-fed beef, poultry or wild-caught fish.
Risks of taking vitamin B12 injections include taking unnecessarily high amounts (which aren’t always absorbed properly anyway) and experiencing interactions with other medications.


https://draxe.com/b12-injections/

Friday, 13 January 2017

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

Thursday, 12 January 2017

Neurofeedback May Well Be An Option For Neuropathy Patients

Today's short post from curetoday.com (see link below) will either interest you because you're open-minded enough to embrace the concept, or put you off because it all seems just a little too 'New Wave'. I fall somewhere in the middle but the idea of neurofeedback as a means of reducing drug intake and at the same time reducing pain, is a very attractive one that maybe deserves more respect than we at first give. The idea is that we can learn over time, to modify our pain responses subliminally and literally feel less pain because the brain reduces its own response to the symptoms. Worth a read to see what you think but if we're going in the direction of a more holistic approach to our nerve pain, then this deserves to be considered as part of the package. Still at the beginning stages.

That Tingling Feeling: New Therapies Are Evolving for Peripheral Neuropathy
MARILYN FENICHEL PUBLISHED: OCTOBER 21, 2016

Excitement is growing over new strategies for treating or avoiding peripheral neuropathy in patients with cancer.

Continue the conversation on CURE’s forum. >>

Talk about this article with other patients, caregivers, and advocates in the Breast cancer CURE discussion group.

During a neurofeedback session, small electroencephalogram (EEG) sensors are placed on the scalp and then connected to a computer. The sensors can track and record brain wave patterns. The participant then plays a series of computer games, with the goal of modifying aberrant waves. When a brain wave has been successfully modified, the participant receives a reward, either by hearing an appealing sound or viewing a pretty picture.

“This kind of learning is unconscious,” explains Prinsloo. “We find that, with repeated practice, usually over a period of 20 sessions, each lasting 30 minutes, the brain learns a new, healthier response to pain and numbness.”

Felecia Peters, 51, was recruited by MD Anderson to participate in its study for breast cancer patients. Diagnosed with stage 2 breast cancer in 2013, she started experiencing symptoms of CIPN while undergoing chemotherapy with Abraxane.

“It snuck up on me,” Peters recalls. “I had numbness, tingling and a sharp, stabbing pain in my feet that would come and go pretty quickly. Balance was also an issue. Sitting down and getting up was painful, as was using my hands to button things and put on small earrings. It hasn’t gone away since my treatment ended two years ago.”

The neurofeedback sessions were not difficult, though Peters remembers feeling sleepy sometimes. “The doctors wanted me to stay awake, but suggested that I nap when I got home,” Peters says. “They said that resting helps the brain remember what it just learned. Unfortunately, I wasn’t always able to follow that advice.”

After completing the 20 neurofeedback sessions, Peters has noticed a significant improvement; she hasn’t felt pain in a while, going up stairs is easier, her fine motor skills are better and she can also exercise more easily.

“I always walked, but now my feet don’t feel as heavy,” says Peters. “While I never fell, it was hard to feel what you were stepping on. It’s a weird feeling, hard to describe.”

As Prinsloo continues to work with women like Peters, she is optimistic that neurofeedback can make a difference.

“Neuropathy is a really debilitating condition,” Prinsloo says. “We’ve seen patients who can’t drive, button their clothes or get around without walkers. They can’t dance or enjoy life as much as they would like. I’m hopeful that our approach will provide these women with lasting relief.”

http://www.curetoday.com/publications/cure/2016/breast-2016/that-tingling-feeling-new-therapies-are-evolving-for-peripheral-neuropathy?p=5

That Tingling Feeling: New Therapies Are Evolving for Peripheral Neuropathy

Excitement is growing over new strategies for treating or avoiding peripheral neuropathy in patients with cancer.
MARILYN FENICHEL
PUBLISHED: OCTOBER 21, 2016
Talk about this article with other patients, caregivers, and advocates in the Breast cancer CURE discussion group.
During a neurofeedback session, small electroencephalogram (EEG) sensors are placed on the scalp and then connected to a computer. The sensors can track and record brain wave patterns. The participant then plays a series of computer games, with the goal of modifying aberrant waves. When a brain wave has been successfully modified, the participant receives a reward, either by hearing an appealing sound or viewing a pretty picture.

“This kind of learning is unconscious,” explains Prinsloo. “We find that, with repeated practice, usually over a period of 20 sessions, each lasting 30 minutes, the brain learns a new, healthier response to pain and numbness.”

Felecia Peters, 51, was recruited by MD Anderson to participate in its study for breast cancer patients. Diagnosed with stage 2 breast cancer in 2013, she started experiencing symptoms of CIPN while undergoing chemotherapy with Abraxane.

“It snuck up on me,” Peters recalls. “I had numbness, tingling and a sharp, stabbing pain in my feet that would come and go pretty quickly. Balance was also an issue. Sitting down and getting up was painful, as was using my hands to button things and put on small earrings. It hasn’t gone away since my treatment ended two years ago.”

The neurofeedback sessions were not difficult, though Peters remembers feeling sleepy sometimes. “The doctors wanted me to stay awake, but suggested that I nap when I got home,” Peters says. “They said that resting helps the brain remember what it just learned. Unfortunately, I wasn’t always able to follow that advice.”

After completing the 20 neurofeedback sessions, Peters has noticed a significant improvement; she hasn’t felt pain in a while, going up stairs is easier, her fine motor skills are better and she can also exercise more easily.

“I always walked, but now my feet don’t feel as heavy,” says Peters. “While I never fell, it was hard to feel what you were stepping on. It’s a weird feeling, hard to describe.”

As Prinsloo continues to work with women like Peters, she is optimistic that neurofeedback can make a difference.

“Neuropathy is a really debilitating condition,” Prinsloo says. “We’ve seen patients who can’t drive, button their clothes or get around without walkers. They can’t dance or enjoy life as much as they would like. I’m hopeful that our approach will provide these women with lasting relief.”
- See more at: http://www.curetoday.com/publications/cure/2016/breast-2016/that-tingling-feeling-new-therapies-are-evolving-for-peripheral-neuropathy?p=5#sthash.uMbx0EUT.dpuf