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Alternative Therapies

A new electric device is being tested for the treatment of migraine by an Israeli company, Theranica. Transcutaneous electric nerve stimulation (TENS) has been successfully used for the treatment of musculoskeletal disorders for decades. The theory behind it is the so-called gate theory of pain. It is thought that by stimulating larger nerve fibers we can block pain messages sent by smaller pain-sensing nerve fibers.

Cefaly is a TENS device which became available in 2014 and it provides electrical stimulation of the supraorbital nerves in the forehead. Only small studies have been conducted, so it is not clear how well Cefaly relieves migraines. As far as our experience, we at the NY Headache Center usually treat more severely affected patients, so it is possible that the results are better in people with less severe migraines.

The new wireless patch that is being developed by Theranica is applied to the upper arm. The results of the first study of this patch were published in Neurology, the medical journal of the American Academy of Neurology.

The study author, is a well-known neurologist and pain researcher, Dr. David Yarnitsky of Technion Faculty of Medicine in Haifa, Israel. He was quoted saying, “People with migraine are looking for non-drug treatments, and this new device is easy to use, has no side effects and can be conveniently used in work or social settings.”

The patch device is controlled by a smartphone app. It was studied in 71 patients with episodic migraine who had two to eight attacks per month and who were not on any preventive medications for migraines. The device was applied soon after the start of a migraine and kept in place for 20 minutes.

The devices were programmed to randomly give either a very weak stimulation to serve as placebo or different levels of stronger electrical stimulation.

A total of 299 migraine attacks were treated by these 71 patients. Two hours after the start of real treatment, pain was reduced by at least 50% in 64 percent of patients, compared to 26 percent of patients who received the sham stimulation.

Starting treatment early produced better results, which is similar to what we see with all migraine medications as well. None of the participants found the treatment to be painful.

The device is very safe and we hope that the ongoing trial that Theranica is conducting in the US will confirm its efficacy. It is not yet available in this or any other country.

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Naltrexone, along with naloxone are narcotic (opioid) antidotes, that is they counteract the effect of narcotics and are used to treat overdoses with heroin, fentanyl, Percocet, Vicodin, and other opioid drugs. Surprisingly, low doses of naltrexone (LDN) seem to be effective in treating pain. LDN has been also used to treat symptom in conditions such as depression, fibromyalgia, Crohn’s disease, multiple sclerosis, complex regional pain syndrome (which used to be called reflex sympathetic dystrophy), and autoimmune disorders.

Low dose naltrexone is not a typical pain killer, but may be helping pain by reducing inflammation. Instead of opioid receptors, it works on Toll-like receptor 4 (TLR4) receptors on glial cells. Glial cells surround the nerve cells and play important functions in the brain, beyond just a supporting role that had been assigned to them for many years. Opioid drugs are known to promote inflammation through the brain immune system leading to worsening of pain over time. Recent discoveries have shown that the Toll-like receptors are involved in triggering these inflammatory immune events. These discoveries have led many researchers to look at ways to block TLR4, but so far no such drug has been developed. We do have several existing medications that seem to block TLR4. Besides LDN, amitriptyline (Elavil) and cyclobenzaprine (Flexeril) are two other drugs that block TLR4 and that have been used for years to treat pain.

No large controlled studies of LDN for migraines, pain or any other condition have been conducted to date. Despite the fact that the evidence is only anecdotal and that LDN my work purely through the placebo effect, advantages of LDN are that it is inexpensive and safe. Naltrexone is available in 25 and 50 mg tablets, while the amount used for LDN is between 1.5 to 4.5 mg. This means that it can be obtained only from a compounding pharmacy. Naltrexone is not a controlled substance, but it does require a prescription from the doctor.

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Italian researchers published a study in the journal Headache that attempted to correlate the attachment style in children with migraines with headache severity and psychological symptoms.

Attachment style typically develops in the first year of life. The premise of the study was derived from the attachment theory which suggests that early interpersonal relationships may determine future psychological problems and painful conditions. Previous studies have shown that people with insecure attachment styles tend to experience more pain than people with secure attachment style.

The study involved 90 children with migraines. The mean age was 12 years and there were 54 girls and 36 boys in the study. The kids were divided into a group with very frequent headaches (1 to 7 a week) and those with infrequent attacks – 3 or fewer per month. They also grouped them into those with severe pain, which interrupted their daily activities and those with mild pain that allowed them to function normally. The children were tested for anxiety, depression, and somatization (tendency to have physical complaints as a manifestation of psychological distress). They were also evaluated for the attachment style and were assigned into “secure,” “avoidant,” “ambivalent,” and “disorganized/confused” groups.

Interestingly, the researchers found a significant relationship between the attachment style and migraine features. Ambivalent attachment was present in 51% of children with high frequency of attacks and in 50% of those with severe pain. Anxiety, depression, and somatization were higher in patients with ambivalent attachment style. They also showed an association between high attack frequency and high anxiety levels in children with ambivalent attachment style.

The authors concluded: “We found that the ambivalent attachment style is associated with more severe migraine and higher psychological symptoms. These results can have therapeutic consequences. Given the high risk of developing severe headache and psychological distress, special attention should be paid to children with migraine showing an ambivalent pattern of attachment style. Indeed, a prophylactic and psychological therapy could often be necessary for these patients.”

People who have an anxious–ambivalent attachment style show a high desire for intimacy but often feel reluctant about becoming close to others and worry that people will not reciprocate their feelings. It is possible to mitigate the negative effects of the ambivalent attachment style even in adulthood. It does require a major effort and help from a psychotherapist.

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Atul Gawande is a surgeon at the Brigham and Women’s Hospital in Boston and a professor at Harvard Medical School. He is also a very talented writer who has written four books and has been writing for the New Yorker since 1998. I had the privilege of meeting him and found him to be very humble and low-key, despite him being a surgeon, MacArthur “genius” award recipient, famous writer, etc. His last book, Being Mortal should be read by everyone who is dealing with elderly parents, grandparents, or friends.

His last article in the New Yorker, The Heroism of Incremental Care describes how headache specialists approach patients with severe and persistent migraine headaches. Fortunately, these are a minority of our patients, but require our unflagging attention and care. Some tell me that they’ve tried “everything” and ask, “please do not abandon me”. My response is to reassure the person that I will never stop trying to help and also that I’ve never seen anyone who has tried everything – we always find medications, supplements, devices, procedures, and other treatments that the patient has not yet tried.

Just like with the man in Gawande’s story, some patients improve very slowly and over a long period of time, so patience and perseverance are essential. I must admit that we cannot be sure if it is our treatment or just the passage of time that leads to improvement. However, it may not matter since our support helps avoid a sense of helplessness and hopelessness that can lead to depression and a decline in the ability to function.

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Many chiropractors advertise their success in treating migraine headaches. Norwegian researchers conducted a scientific study of chiropractic manipulation for migraine headaches in 104 patients. They divided patients into three groups: one that received real chiropractic manipulation of the spine, one that received a sham treatment that consisted of just putting pressure over the shoulders and lower back, and one that continued their usual medication. The real and sham chiropractic groups received 12 treatment sessions over 12 weeks and all three groups were followed for a year. After 12 weeks patients in all three study groups reported improvement. However, a year later, only the two chiropractic groups still felt better. On average, they had about four migraine days a month, down from six to eight before the treatment started. Patients who just continued their medications lost all of their improvement and their migraine frequency was back where it was at the baseline.

The results published in the European Journal of Neurology suggest that chiropractic is indeed effective in reducing migraine frequency, however, it also suggests that any hands-on treatment is equally effective. This probably explains the popularity of chiropractic, physical therapy, massage, reflexology, Reiki, energy therapies, Feldenkreis, and all other hands-on treatments.

All these treatments are worth trying, but avoid high velocity adjustments when undergoing chiropractic treatment as it carries a small risk of serious side effects (see this previous post). I would also pick inexpensive treatments and pick therapists you feel a rapport with. The treatment should be pleasant and never painful. You should also combine these therapies with a healthy lifestyle, including a healthy diet, regular sleep, exercise, meditation, and supplements.

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Vitamin C deficiency appears to be more common in people with back pain, according to a study just published in the journal Pain by Canadian researchers. Vitamin C (ascorbic acid) is important for collagen formation and collagen is one of the main ingredients of ligaments, tendons, and bones. Recent studies have reported that vitamin C deficiency is common in the general population. The authors “hypothesized that lack of vitamin C contributes to poor collagen properties and back pain”. They used nationwide data from the U.S. National Health and Nutrition Examination Survey from 2003–2004. Information was available for 4,742 individuals older than 20. Low serum vitamin C levels were associated with one and a half times higher prevalence of neck pain and 1.3 times higher prevalence of low back pain, as well as low back pain with pain radiating to below the knee in the preceding three months. Deficiency was also associated with the self-described diagnosis of arthritis or rheumatism and related functional limitations. The authors concluded that the association between vitamin C deficiency and spinal pain warrants further investigation to determine the possible importance of vitamin C in the treatment of back pain patients.

Neck pain is very common in patients with migraine and tension-type headaches, so it is possible that vitamin C could also play a role in the treatment of headaches. My search revealed no studies looking at vitamin C levels in migraine sufferers. It may be worth checking vitamin C levels in those headache patients who do not respond to usual treatments and recommending supplementation to those who are deficient. However, even if I see good responses to vitamin C in my patients, these observations are not going provide true scientific evidence, even if hundreds of my patients report feeling better. This is because besides giving vitamin C, I would continue to recommend regular exercise, healthy diet, meditation, and other vitamins and minerals, all of which could be contributing to improvement. We need a large study to measure vitamin C levels in headache patients, and the deficient patients should be enrolled in a double-blind study to find out if vitamin C can improve different types of headaches.

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Two leading headache experts, Drs. Richard Lipton and Dawn Buse of the Montefiore Headache clinic gave positive comments on the report published in Pain and described in my recent post. Another headache specialist from Texas, Dr. Deborah Friedman was also quoted about this research report in Neurology Today.

“Acupuncture studies are difficult because the blinding is difficult,” Richard B. Lipton, MD, FAAN, the Edwin S. Lowe professor and vice chair of neurology at the Albert Einstein College of Medicine, said. He noted that even comparisons using sham procedures may not entirely blind the patient to whether he or she is receiving a real treatment in which needles are inserted in the “meridian” — the points where energy is said to flow.“ That said, the authors in their review show that acupuncture is very substantially better than usual care. I think in aggregate these data demonstrate that real acupuncture is very helpful to people with episodic migraine in terms of reducing the number of headache days. My longstanding practice has been to arrange acupuncture for patients who ask for it, but not to recommend it otherwise,” Dr. Lipton said. “This review is going to impact what I do. It’s 22 randomized trials, and the Cochrane review is 150 pages. I think this is an important summary of the best evidence. I think it’s quite positive. I want to make my patients better so the imperfect blinding doesn’t matter.”

Dawn C. Buse, PhD, associate professor of neurology at Albert Einstein College of Medicine of Yeshiva University, also found the review persuasive, while noting that the mechanism by which acupuncture works is unknown and may be influenced by factors other than the procedure itself. “This review demonstrates that acupuncture may be helpful in reducing the frequency of migraine attacks and is likely to be well tolerated when compared to pharmacologic treatment,” she said. “We do not know from this review how patients who incorporate both acupuncture and optimized pharmacologic approaches fare. However, we know from meta-analyses of combined behavioral and pharmacologic approaches to migraine management that the combination is superior to either approach alone both in initial and sustained response.” She added: “Evidence suggests that many additional factors unrelated to acupuncture needling including expectations, beliefs, openness to experience, and the quality of the patient-provider relationship may play important roles in the beneficial effects of acupuncture for a particular patient. In addition, it is likely that patients who participate in and as a result report benefit from acupuncture are people who are interested and open to nonpharmacologic approaches. It is likely a patient who is open to nonpharmacologic approaches may also be a patient who will take a more active role in migraine management.” Dr. Buse noted that this type of patient is likely to have better treatment outcomes, no matter what type of treatment, due to higher levels of self-efficacy and willingness to actively engage in all aspects of treatment such as following treatment recommendations for healthy lifestyle habits, exercising, managing stress and healthy sleep hygiene. “Based upon these findings, it is reasonable to suggest that a patient who is interested and motivated to try acupuncture to manage migraine may benefit,” she told Neurology Today. “There are likely to be few if any side effects or risks to acupuncture, other than time and financial expense since acupuncture may not be covered by insurance. In addition, it may be difficult to advise a patient how to find a provider with proper training, skill, and knowledge to provide successful treatment and to know exactly what successful treatment would entail. The body of literature suggests that combined pharmacologic plus behavioral approaches are superior to either one alone, Dr. Buse noted. It may be therefore wise to recommend that patients who are interested in acupuncture combine it with optimized pharmacologic and behavioral treatments for the best chance of treatment outcome with lasting benefits, she said.

Dr. Lipton echoed that comment. “Acupuncture is one of many nonpharmacologic treatments for migraine,” he said. “The nonpharmacologic interventions include education, helping people identify triggers, some vitamins and herbs that are evidence-based, cognitive-behavior therapy and biofeedback. So my broad comment is that we should not restrict what is in our toolbox and consider a range of non-pharmacologic as well as pharmacologic treatments.”

But another reviewer, Deborah I. Friedman, MD, MPH, FAAN, chief of the division of headache medicine and professor of neurology & neurotherapeutics and ophthalmology at University of Texas-Southwestern in Dallas, expressed some reservations about the quality of the data. “Acupuncture is helpful in some patients with episodic migraine, particularly as an ‘add on’ treatment, but the quality of the data from clinical trials is moderate overall. There is a lot of variability in acupuncture technique amongst practitioners,” she said. “Patients who are interested in acupuncture should be referred to reputable practitioners who have had proper training.” She added: “In general, I don’t discourage it, but I rarely suggest it as an option unless the patient asks about it, or if I get the sense that they are interested in natural remedies. I tell my patients that the clinical evidence to support acupuncture treatment for migraine is not strong, with mixed results. However, it is safe and many patients find it useful, particularly those who are attracted to ‘natural’ or non-pharmacological treatments, and those who have not tolerated conventional therapies.” Dr. Friedman said that in the program at University of Texas Southwestern Medical Center, physical therapists are trained to do dry needling. “It seems to benefit many of our patients with refractory head and neck pain,” she said. “I make it clear to my patients that this is not the same as traditional acupuncture, and encourage them to try it once to see if it helps.”

Dr. Linde, one of the authors of the original report, noted in his comments that the problem of blinding affects the study of many treatments that are not pharmacologic in nature. “While the overall quality of a number of trials is actually quite good, one has to keep in mind that apart from sham-controlled trials acupuncture studies are usually not blind. However, this applies to almost all non-pharmacological treatments.”

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Acupuncture for the treatment of migraines has been studied in dozens of clinical trials. A 2012 study mentioned in a previous blog post described a rigorous trial done in 480 patients with highly positive results. The largest, albeit uncontrolled study was done in Germany and involved over 15,000 patients. A well controlled and randomized study of 960 patients comparing acupuncture with sham acupuncture and drug therapy concluded that “…acupuncture is as effective as drug therapy, but …sham acupuncture is as effective as ‘real’ acupuncture.” and “…acupuncture should be offered to patients who do not respond to prophylactic treatment with drugs, terminate drug treatment because of adverse events or have contraindications to drug treatment.”

Most headache specialists recommend acupuncture to their patients even if they believe it works only through the placebo effect. I’ve been a licensed acupuncturist for the past 30 years, but treat a relatively small number of patients with acupuncture. The main reasons are the fact that insurance companies do not pay for it and that it is too time consuming. In the first study mentioned above, which was performed in China, patients were treated five days a week. The minimum frequency of treatments should be once a week. I often recommend that patients find a non-MD acupuncturist (whose rates are usually lower) who is closer to the patient’s home or work place. Another concern with acupuncture is that while it might help during the treatment, the effect might subside once the treatment is stopped.

A study The persistence of the effects of acupuncture after a course of treatment: A meta-analysis of patients with chronic pain, just published in the journal Pain addresses this question.

A group of researchers from the US and Europe examined a large set of information on individual patients from high quality randomized trials of acupuncture for chronic pain. The chronic pain conditions included musculoskeletal pain (low back, neck and shoulder), osteoarthritis of the knee and headache / migraine. Data on longer-term follow-up were available for 20 trials, which included 6,376 patients. In trials comparing acupuncture to no acupuncture control (wait-list, usual care, etc), the treatment effect diminished by a very small amount after treatment ended. They estimated that 90% of the benefit of acupuncture relative to controls would be sustained at 12 months. For trials comparing acupuncture to sham acupuncture, they observed a higher reduction in effect, suggesting about a 50% diminution at 12 months. They concluded that “The effects of a course of acupuncture treatment for patients with chronic pain do not appear to decrease importantly over 12 months. Patients can generally be reassured that treatment effects persist.” They also suggested that studies of the cost-effectiveness of acupuncture should take these findings into account when considering the time horizon of acupuncture effects and that further research should measure longer term outcomes of acupuncture.

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Medical marijuana was legalized in New York in February of this year. Since then, I’ve prescribed it to over 30 patients and about a third of them have found it to be effective. We are planning an observational study to determine which of the three approved types (inhaled, sublingual, oral) and what ratio of active ingredients (THC/CBD) are preferred by migraine sufferers. Doctors who prescribe medical marijuana do have to take an online training course, but the course does not teach about the optimal use because no one has researched this question. There are also regulatory issues to deal with.

Several sets of guidelines have been published by various medical organizations addressing the proper use of medical marijuana, other than dosing and route of administration. Here are some of the recommendations with my comments:

“The doctor should adhere to current standards of practice and comply with state laws, rules and regulations, which may specify conditions for which a patient may quality.”
Migraine is not one of the conditions listed specifically, but it is often accompanied by neuropathic pain, which is listed.

“The doctor’s office should not be located at a marijuana dispensary or cultivation center. The doctor should not receive financial compensation from or hold a financial interest in marijuana-related businesses or be affiliated with them in any way.”
This one is easy for us.

“The physician should not use marijuana either medicinally or recreationally while actively engaged in the practice of medicine.”
I’ve never tried it.

“There should be an established doctor-patient relationship before the doctor considers the use of medical marijuana.”
I prescribe it only to our established patients.

“The doctor should do a physical exam and gather health history, including documentation of previous therapies used by the patient and information on any personal or family history of substance abuse, mental illness or psychotic disorders. The diagnosis should justify the consideration of medical marijuana.”
All of our patients undergo a thorough evaluation.

“The doctor should review other treatment options. The known benefits and risks of marijuana should be presented, along with the warning that, unlike with FDA-approved drugs, there is variability and lack of standardization in marijuana preparation.”
We use medical marijuana only after other non-drug and drug treatments fail.

“If the medical marijuana is chosen, a specific treatment plan for a limited period of time should be agreed on, with details documented in the medical record. The doctor should instruct the patient not to drive or operate heavy machinery while using marijuana.”
Yes, I do that.

“The patient should be seen for follow-up visits to monitor for efficacy and side effects of medical marijuana.”
This is a standard practice with any treatment.

“Patients with a history of mental health problems, substance abuse or addiction should be referred for further evaluation as needed.”
I typically avoid prescribing medical marijuana to such patients.

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We are big proponents of non-drug treatments, including a variety of vitamins, minerals, and herbal supplements. However, potential liver damage by butterbur is why we do not recommend this supplement, even though I was one of the participants in the clinical trial that showed it to be effective in preventing migraines. I also cautioned about risks of some Ayurvedic medications.

A recent report in Hepatology, a journal devoted to liver diseases, suggests that 20% of all cases of liver damage are due to herbal and dietary supplements. The main culprits were anabolic steroids (these are banned in professional sports, but are widely used for muscle building), green tea extract, and supplements with multiple ingredients. Anabolic steroids cause prolonged, but not serious liver injury, which resolves when the supplement is stopped. Green tea extract and many other products cause acute liver damage, similar to that seen in hepatitis. The majority of cases of liver injury are due to products that contain multiple ingredients, which makes it difficult to figure out which of the supplements is responsible. Unfortunately, non-prescription supplements are not regulated by the government. This is mostly because it is a $37 billion dollars a year industry with a powerful lobby in Washington. The authors conclude their report by saying that “the ultimate goal should be to prohibit or more closely regulate potentially injurious ingredients and thus promote public safety.”

Until these products come under FDA’s supervision, you should buy only products made by reputable American and German companies. Germany tightly regulates their supplement industry, so if a product is sold in Germany (and none of the butterbur products are approved there or in Great Britain), it is probably safe to take. Do not buy products made in China where corruption has led to many scandals related to the quality of supplements, drugs, food, and environmental pollution.

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Medical marijuana reduces the number of prescriptions written by doctors, according to a recent study published in Health Affairs. The researchers at the University of Georgia in Athens looked at all prescriptions filled by Medicare participants over a four year period for nine conditions for which medical marijuana is used for. These included anxiety, depression, glaucoma, nausea, pain, psychosis, seizures, sleep disorders and spasticity. They compared 17 states and Washington, DC where medical marijuana was legalized with those where it was not. In states with legalized medical marijuana the number of prescriptions dropped by 0.5% providing estimated savings of $165 million a year. Of all approved indications, relief of pain was by far the most common reason medical marijuana was prescribed for. This was a much more dramatic effect than the researchers anticipated. They expected that the mostly elderly patients on Medicare would be more resistant to the idea of using marijuana than younger people.

In a February post I mentioned that I started prescribing medical marijuana to my patients with migraine headaches who also have neuropathic pain as part of their headache. While medical marijuana is not approved for migraines per se, it is approved for neuropathic (i.e nerve-related pain), which many migraine sufferers do have. Burning or stabbing pain indicates the presence of neuropathic pain. So far, I’ve prescribed medical marijuana to about two dozen patients and as expected, the results are mixed. It works well for some, but not other. Most commonly, patients who’ve had positive experience with recreational marijuana tend to request medical marijuana and they tend to do better than those who’ve never tried it.

Research on medical marijuana is complicated by the fact that there is no standard formulation, which means that there is wide variation in the strains of the plant with varying amounts of active and inactive ingredients. In New York State medical marijuana can be ingested, inhaled through a vaporizer or placed under the tongue. We also have various ratios of tetrahydrocannabinol (THC) and cannabidiol (CBD), which produce different results. Nevertheless, we do plan to do an observational study of 100 migraine sufferers who also have neuropathic pain. We hope to get an indication as to what route of administration and what THC/CBD ratio work best for migraine patients.

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Vitamin B12 was the subject of an article in the New York Times by Jane Brody entitled, Vitamin B12 as Protection for the Aging Brain. However, she mentions that “insufficient absorption of B12 from foods may even be common among adults aged 26 to 49” and that the advice to take a vitamin B12 supplement may apply to young people as well. This is particularly true for vegans and vegetarians, as well as people with stomach problems and those on PPIs – drugs for ulcers and heartburn, such as Prilosec, Nexium, Aciphex, etc.

Vitamin B12 deficiency can cause “fatigue, tingling and numbness in the hands and feet, muscle weakness and loss of reflexes, which may progress to confusion, depression, memory loss and dementia as the deficiency grows more severe”. Severe deficiency leads to peripheral and central nervous system damage (so called subacute combined degeneration), which eventually becomes irreversible and leads to death.

Jane Brody does not mention that besides Alzheimer’s, other chronic diseases, such as multiple sclerosis, diabetes, and cancer are also associated with low vitamin B12 levels. Vitamin B12 with vitamin B6 and folic acid has been shown to help some migraine sufferers

You can ask your doctor to check your vitamin B12 level, but unfortunately it is not reliable. Most laboratories cite as normal blood levels of above 200 or 250, but there are reports of rare cases where severe deficiency is present with a level of 700. I recommend taking a supplement if the level is below 500. In severe cases or in people with stomach problems, a monthly injection is a better choice. Patients can easily self-inject vitamin B12, but it does require a doctor’s prescription. Some of my patients feel the need to inject themselves with vitamin B12 more often than once a month. Whenever they start feeling tired or having other symptoms, they take a shot. Unlike some vitamins, such as B6 and A, vitamin B12 does not cause any negative effects even at high levels. As an oral supplement I usually recommend tablets of methylcobalamin, rather than cyanocobalamin form of vitamin B12 because of better absorption. The usual dose is 1 mg (or 1,000 mcg) daily. If you are deficient and stop taking the supplement, the deficiency can return within a few months.

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