Methylcobalamin is an essential nutrient and is needed to treat vitaminB12 deficiency in people with pernicious anemia, diabetes and other disorders but the ban imposed on methylcobalamin warrants scrutiny in the wake of dual standards followed by the regulatory authorities. FSSAI has been drawing flak from the industry because of the ban on methylcobalamin which has rather become a contentious issue today. There is also a nationwide ban on methylcobalamin by state drug regulators citing that FSSAI has imposed the ban based on ICMR recommendation.

On behalf of the nutraceutical industry, Dr. Sanjay Agrawal has repeatedly urged the country’s apex food regulator and other Government authorities with numerous correspondences to revoke the ban on Methylcobalamin but till date they haven’t received a favorable reply from the concerned authority.

The recommended dietary allowance value and upper tolerance limit of Methylcobalamin fixed by the autonomous body (FSSAI) under the Ministry of Health & Family Welfare is unclear too, leading to total confusion in the nutraceutical industry. Once methylcobalamin is notified, the approved recommended dietary allowance value can be defined in a scientific way, based on evidence.

The industry has argued for clarity on the technical aspect under which, methylcobalamin,on one hand is approved as a drug with recommended dietary allowance value of 2000 mcg,whereas for nutraceuticals,it has been permitted with recommended dietary allowance value of 1 mcg only.DCGI recommends 2000 mcg of methylcobalamin even in injectable form and brands are also available as patients take methylcobalamin based on their medical condition.

Also the issue on missing exact information on tolerable upper limit of vitamin B12 or methylcobalamin for neurological disorders and in boosting immunity has been festering in the public domain.

Gujarat state based many nutraceutical manufacturers have alleged that the dual standards of FSSAI is very much evident with the presence of FSSAI approved brands of methylcobalamin in the market with 1500 microgram (mcg) quantity/per serving. Some of the widely sold brands are Rejunex CD3,Locopen capsule, Neugaba M 75 capsule, Nervup 500 mcg injection, Nuroz Forte, Nurofine 2500 injection, Actavis 2500 injection, etc. There are more than half a dozen of other brands with the same formula.

On January 7, 2020, FSSAI had issued a notification regarding recommended dietary allowance value of vitamin B12 which is specified as 1 mcg without mentioning type of vitamin B12 like methylcobalamin, adenosylcobalamin, hydroxycobalamin and cyanocobalamin. But the Drugs Controller General of India has recommended 2000 mcg of methylcobalamin in injectable form and respective brands are available as physicians are prescribing it for patients.

Previously, in a draft guideline issued in 2017, which is also considered as extension of regulation 2016, the FSSAI added the word ‘derivatives of vitamins’ to the approved list. Manufacturers continued to manufacture methylcobalamin considering it as a derivative of methylcobalamin.

The Section 22 of FSS Act, 2006 mentions foods for special dietary uses or functional foods or nutraceuticals or health supplements shall contain minerals or vitamins or proteins or metals or their compounds or amino acids in amounts not exceeding the recommended dietary allowances for Indians. As the regulations are bound to follow provisions mentioned under Act, the same has been enshrined into the Food Safety and Standards (Health Supplements, Nutraceuticals, Food for Special Dietary Use, Food for Special Medical Purpose, Functional Foods and Novel Foods) Regulations 2016.

But, in a letter to the FSSAI, CDSCO brought to the notice that various brands of products containing methylcobalamin are manufactured and sold having therapeutic intervention under the FSSAI license.The CDSCO had then urged the FSSAI to take action against Gujarat-based manufacturers for manufacture and sale of methylcobalamin meant for therapeutic intervention in contravention of norms.

Recently Dr Sanjay Agrawal has raised alarm on the blatant violation of administrative protocols in the regulatory regime in India citing the FSSAI’s directive to all State Drug Controllers to take action against manufacturers for production and sale of methylcobalamin meant for therapy in cases of diabetes and neurological disorders, in contravention to norms.

According to him, it is evident that the issue about taking action on methylcobalamin manufacturers is totally uncalled for and it indicates lobbying and malafide intent to discourage the industry to satisfy vested interests.

Thus, in a recent representation made to Union Ministry of Chemicals and Fertilizers, Dr Agrawal has recommended the Drugs Controller General of India (DCGI) to be given the sole authority for implementation of nutraceutical policies and regulations citing both FSSAI and ICMR as toothless authorities, giving reference that ten years back the nutraceutical industry was under the DCGI only and was well regulated.

He further mentions in the letter, ‘it is pertinent to mention here that there are only two variants of vitamin B12 namely cyanocobalamin and hydroxycobalamin which are covered under Food Safety and Standards (Health Supplements, Nutraceuticals, Food for Special Dietary use, Food for Special Medical Purpose, Functional Food And Novel Food Regulation 2016) (FSSAI-2016) but does not cover methylcobalamin’.

Few months ago, Dr Agrawal had also urged the Union Minister of Chemicals and Fertilizers to urgently notify methylcobalamin for neurological disorders and informed that regulatory action cannot be taken against those who are manufacturing methylcobalamin-based formulations without scientifically defining the efficacious recommended dietary allowance value.

According to nutraceutical industry experts, no adverse effect has been associated with excess methylcobalamin intake from food or supplements in healthy individuals. Methylcobalamin has a history of safe long term use as a therapeutic agent given in high dosage or via intramuscular injection for the treatment of disorders associated with impaired vitamin B12 absorption but industry is yet to see the much awaited notification on the same.

Dr Agrawal has been pursuing the issue of revoking the ban on methylcobalamin by FSSAI for more than a year but yet this issue has not come to a logical conclusion. On the contrary, FSSAI has allowed usage of cyanocobalamin- which has cyanide content within, but banned methylcobalamin- which is a superior form of vitamin B12.

Dr Agrawal has again sought clarity from FSSAI on Indian Council of Medical Research stipulated values of recommended dietary allowance value for methylcobalamin as prophylactic use in neurological disorders. Dr Agrawal’s recent correspondences to FSSAI in spite of being addressed in a holistic manner have turned into a blame game between FSSAI and ICMR.

According to sources, taking an entirely U-turn, the national food safety regulator has instead directed the industry to refer the issue to the ICMR in blatant denial of laid down protocols and ethics. This is leading to confusion and hence detrimental to the public interest.

Industry, after almost more than a year, is still perplexed with FSSAI clarification regarding recommended dietary allowance values on methylcobalamin (vitamin B12). Any food business operator who wants to manufacture, import, market or sell the afore mentioned products shall have to comply with the provisions of these regulations.

Dr Agrawal had received a letter in December 2019 from FSSAI about Methylcobalamin being soon to be approved and to be provided recommended dietary allowance value of it for neurological disorders, but industry is yet to see the much awaited notification on the same.

Even as the notification regarding approval of the right recommended dietary allowance value for methylcobalamin remains pending for almost more than a year despite FSSAI scientific panel’s nod of notifying it in last December, the drug and nutraceutical industry rues that the nationwide ban on methylcobalamin has proved to be an extortion bid by state drug controllers in the guise of regulations.

This is all the more contradictory considering that ICMR and National Institute of Nutrition have recently issued another report which have different stipulated recommended dietary allowance values of methylcobalamin and estimated average nutrient requirements for Indians. In the Norwegian Vitamin (NORVIT) intervention trial also, patients with acute myocardial infarction received 400 mcg of vitamin B12 daily for three years and reported no serious adverse events.

On behalf of the nutraceutical industry, Dr Agrawal is planning to again make a representation on this matter with the Union Ministry of Chemicals and Fertilizers since their previous correspondences (December 2019 and June 2020) and pleas to FSSAI have not been addressed with due diligence and rationality.

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Vitamin C plays an important role as a component of enzymes involved in the synthesis of collagen and carnitine; It acts as a reducing agent to maintain the enzyme prolyl hydroxylase in an active form, most likely by keeping its iron atom in a reduced state. The hydroxylation of proline and lysine in procollagen is carried out by the enzyme prolyl hydroxylase using Vitamin C as a cofactor.

It also helps maintain capillaries, bones, and teeth and aids in the absorption of iron. Vitamin C is the most potent enhancer of non-heme iron absorption. A study showed that iron absorption from non-heme food sources can be increased significantly with a daily Vitamin C intake of at least 25 mg for each meal (estimated for 3 mealzs/day).

Vitamin C is a potent antioxidant because it can donate a hydrogen atom and form a relatively stable ascorbyl free radical. As a scavenger of reactive oxygen and nitrogen oxide species, Vitamin C has been shown to be effective against the superoxide radical ion, hydrogen peroxide, the hypochlorous acid and singlet oxygen.

Get some fruits:

You probably know about oranges, grapefruits, lemons, and limes. But berries rock too — strawberries, raspberries, blueberries, cranberries. Papaya, kiwi, pineapple, cantaloupe, plums, and watermelon are good sources. Even bananas, apples, and pears have some. Eat them fresh and raw. Vitamin C breaks down over time when it’s heated.

Get some veggies:

Think green. Bell peppers are your big C winners. Load up on leafy greens too — kale, Swiss chard, collards, plus cabbage, and bok choy. Crunch into broccoli, cauliflower, and Brussels sprouts. Don’t forget tomatoes, sweet potatoes, and winter squash. If you really have to cook your veggies, stick with steaming or microwaving. These methods tend to keep more of the vitamin’s benefits.

Dynamic duos:

Vitamin C can help other nutrients work better. Put red peppers in your spinach salad. Slip some broccoli in your baked beans. Pair up strawberries with your oatmeal.

Prevent a cold? Nope

Your immune system does need vitamin C to work right. But extra won’t help you avoid a cold. It may make it go away faster or not feel as bad — if you were taking it before you got sick.

Cell Service

Vitamin C helps you get rid of chemicals causing damage inside your body. It helps offset the effects of pollution, cigarette smoke, sunlight, radiation, and even helps turn food into energy. That could help keep things working better for longer and protect you from diseases, including Alzheimer’s and cancer.

Skin game

Your body needs vitamin C to help it make bones, cartilage, skin and muscles (including your heart), ligaments, tendons and blood vessels. Vitamin C is important for new skin and scar tissue when you get cut and to keep you from getting wrinkles.

Gets your brain in gear

You need vitamin C to help carry signals from your brain all over your body. These affect your mood, memory, motivation, and how you feel pain.

Raises Your Sights

The vitamin A in carrots isn’t the only thing that’s good for your eyes. Vitamin C might slow age-related macular degeneration (AMD), but it won’t prevent the disease. C may also cut your risk of cataracts.

Vitamin C vs. the Big C

Very high doses, especially through an IV, may slow the growth and spread of cancer cells. In some case it can help chemotherapy and radiation work better. It may help you feel better and have fewer side effects, too. But be careful. It can also make treatments less effective.

Good for smokers

When you smoke, you’ll have lower levels of vitamin C in your body. Try to get a little extra every day to make up for it. People who are around smokers are also affected and could use more vitamin C, too.

Amount of Vit. C should be taken

Most people who eat a variety of vegetables and fruits daily get more than enough vitamin C from their diet. If you want to take a supplement, look for the inexpensive ascorbic acid form. For prevention   Vit. C 500 mg should be taken twice in a day (1000 mg ) for long duration. Specially in COVID-19 1000 mg twice in a day .

Vit. C is very important as a preventive vitamin against COVID due to its alkaline in nature after metabolism. COVID virus cannot sustain in alkaline medium.

Dr Sanjay Agrawal
Leading Pharmaceutical Consultant
Editor-in Chief of IJM Today

The post Vitamin C – a preventive vitamin against COVID appeared first on Health Vision.

Methylcobalamin is an activated form of vitamin B12 and it has been used to treat nutritional diseases and also some other diseases such as Alzheimer’s disease and rheumatoid arthritis. As an auxiliary agent, it exerts neuronal protection by promoting regeneration of injured nerves and antagonizing glutamate-induced neurotoxicity. Recently several lines of evidence shows that methylcobalamin may have potential analgesic effects in experimental and clinical studies.

A deficiency in vitamin B12 can cause serious symptoms

Vitamin B12 deficiency is observed more in elderly and pregnant women. Methylcobalamin (commonly known as mecobalamin or methyl B12) is an analog of vitamin B12 which treats or prevents the pathology arising from the deficiency of vitamin B12. It contains methyl alkyl bonds and is different from cyanocobalamin because it contains cynide. A deficiency in vitamin B12 can cause serious symptoms, including fatigue, nerve damage, digestive issues, and neurological disorders such as depression and memory loss.

Therefore, it is necessary to turn to vitamin B12 supplements to help, meet the needs and to prevent a deficiency. Methylcobalamin has been used as a supplement in patients with vitamin B12 deficiency and in those with diabetes and other neuropathies. It has been used in clinical studies to reduce serum homocysteine levels, and it is an essential nutrient and is required to treat vitamin B12 deficiency in people with pernicious anaemia, diabetes and other conditions as well. For example, methylcobalamin alleviates pain behaviours in diabetic neuropathy, low back pain and neuralgia, and it improves nerve conduction, promotes the regeneration of injured nerves, and inhibited ectopic spontaneous discharges of injured primary sensory neurons.

It is important for the brain, nerves and for the production of red blood cells and it is the only form of vitamin B12 that can cross the blood brain barrier without bio-transformation. Methylcobalamin is the methyl form of cobalamin obtained from hydroxycobalamin, either by chemical manipulation in the lab or in the body as a natural process. Cyano- and hydroxocobalamin are considered the transport forms of cobalamin, while methylcobalamin and deoxyadenosylcobalamin are the active forms involved in enzymatic reactions. Information suggests methylcobalamin may play a role in immune modulation and in cancer.

Methylcobalamin  used in clinical studies

Methylcobalamin has been used in clinical studies to reduce serum homocysteine levels. Methylcobalamin is the most abundant form in human plasma, whereas in most human tissues, deoxyadenosyl cobalamin is the most abundant, with aquacobalamin coming second. Methylcobalamin plays a key role in maintaining good health. It is needed for integrity of myelin, neuronal function, proper red blood cell formation and DNA synthesis. It is a beneficial drug to most of the common disorders such as cardiovascular disorders, diabetes, anemia, hyperhomocysteinemia and degenerative disorders, diabetic neuropathy, degenerative disorders and in the preliminary treatment of amyotropic lateral sclerosis.

It has been used to treat some nutrition based disease such as dementia and exerts neuronal protection by promoting regeneration to injured nerves. It antagonizes the glutamate induced neurotoxicity and also manifests analgesic effects. It alleviates pain behavior in diabetic neuropathy, low back pain, neuralgia and promotes nerve conduction. It helps the body to use fats and carbohydrates for energy.

Methylcobalamin’s oral administration of 500 mcg three times daily for four weeks results in improvement of peripheral neuropathy and it produces very significant effect after 12 weeks of treatment. An improvement in vibration sense, lower motor neuron weakness and sensitivity to pain is also observed in various studies.

For stress relief, methylcobalamin can be taken in the dose of 500 mcg per day. In the acute cases of neuropathy, dose of 1500 mcg per day can be taken. Dose of 1 mg per day is required to be taken for age related brain decay. Methylcobalamin can be combined with similar dose of folic acid and pyridoxine. Deficiency of vitamin B12 is strictly seen in pure vegetarian, dose of 100 mg day can rebalance its requirement in the intestine. All human being need at least 3 mg per day of this drug for the basic nerve support.

Safe use even at high dosages:

Vitamin B12 has a long history of safe use even at high dosages. At usual dosages, the cobalt and cyanide content are not considered to be toxicologically relevant. Vitamin B12 is obtained from animal products (eg, meat, fish, shellfish, poultry, eggs, milk, and milk products). Tempeh, made from fermented soybeans, contains the beneficial bacteria responsible for producing vitamin B12.

Commercial forms of methylcobalamin are produced in the lab through the conversion of cyanocobalamin. Cyanocobalamin is a synthetic form of vitamin B12 that is not naturally available. It is used more frequently in supplements, as it is considered more stable and cost-effective than other forms of vitamin B12. When cyanocobalamin enters human body, it is converted into either methylcobalamin or adenosylcobalamin, which are the two active forms of vitamin B12 in human body. Vitamin B12 deficiency can be solved with the administration of cobalamin. Usually either cyano- or hydroxo-cobalamin is used to restore normal levels. However, there is no reason to suggest lack of efficacy; and reports exist of therapeutic efficacy of methylcobalamin.

A systematic review shows evidence supporting vitamin B12 supplementation to reduce the risk of diabetes or cardiovascular disease. A 2013 meta-analysis that included 15 studies and 1,106 diabetic patients found combination therapy for 2 to 4 weeks with intravenous alpha lipoic acid 300 to 600 mg/day plus intravenous methylcobalamin 500 to 1,000 mg/day to be superior to methylcobalamin  monotherapy for improving nerve conduction. Similarly, combination therapy with prostaglandin (10 or 20 mcg intravenous), methylcobalamin (500 to 1,500 mcg intravenous/intramuscularly plus lipoic acid (300 or 600 mg/day intravenous) significantly improves nerve conduction velocity compared with combination therapy without the lipoic acid in a 2015 meta-analysis of 18 randomized clinical trials involving patients with diabetic peripheral neuropathy.

A Cochrane systematic review and meta-analysis of antioxidants for male sub fertility identified one double-blind, randomized, parallel study that administered vitamin B12; however, the lack of useable data prevented its inclusion in the meta-analysis. Japanese men with abnormal sperm count or motility received mecobalamin at a dose of either 1,500 or 6,000 mcg/day for 12 weeks. No statistically significant difference was observed in sperm parameters compared to placebo.

Folate and vitamin B12 are essential nutrients which are not synthesized in humans and whose deficiency is considered as heath problem globally such as anemia and neuronal dysfunction. Methylcobalamin (5 mg, 60 mg vegetarian lozenges) is active in the central nervous system outside the mitochondrion and is essential for cell growth and replication. Sometimes the liver cannot convert cyanocobalamin into adequate amount of methylcobalamin needed for proper neuronal functioning. Through enhanced methylation, it exerts its nerve cell protective effect and accelerates its growth. Methylcobalamin is the only form of vitamin B12 that can cross the blood brain barrier without biotransformation, and it converts homocysteine to methionine and reduces the potential to damage. It also forms adenosylcobalamine, the other form of vitamin B12 for mitochondrial energy production.

Working or acting mechanism of methylcobalamin

Methylcobalamin works by functioning in the production of a compound called myelin, which covers and protects nerve fibers, rejuvenates the damaged neuron. Without enough methylcobalamin, myelin sheath does not form properly due to which nerve fibers suffers and people experience irreversible nerve damage. An intrinsic factor made in the stomach, must be present in the intestinal tract to allow its proper absorption. People lacking this factor show vitamin B12 deficiencies such as pernicious anemia (a slow and insidious process that can end in death. Pernicious anemia in fact means ‘leading to death’). Methylcobalamin is used as a cofactor in methionine transferase enzyme, an enzyme which converts amino acid homocysteine to methionine through folate cycle.

Vitamin B12, also known as cobalamin, is an important water-soluble vitamin involved in red blood cell production, brain health, and DNA synthesis. Vitamin B12 has a long history of safe use even at high dosages. Vitamin B12 is obtained from animal products (eg, meat, fish, shellfish, poultry, eggs, milk and milk products). Tempeh, made from fermented soybeans, contains the beneficial bacteria responsible for producing vitamin B12. Methylcobalamin and cyanocobalamin can be converted to other forms of vitamin B12. Both methylcobalamin and cyanocobalamin are reduced to a cobalamin molecule that is converted to the active forms of this vitamin within the cells of the body.

Some researchers recommend treating vitamin B12 deficiency with either cyanocobalamin or a combination of methylcobalamin and adenosylcobalamin due to distinct properties of these latter two forms. Although distinct differences exist between methylcobalamin and cyanocobalamin, both have beneficial effects on health and can prevent vitamin B12 deficiency. Studies find that treating seven vitamin B12-deficient People with oral methylcobalamin normalized vitamin B12 levels in their blood within just 2 months.

Similarly, another study shows that taking cyanocobalamin capsules for 3 months also increased vitamin B12 levels in 10 people with pernicious anemia, a condition caused by impaired B12 absorption. Other some studies show that both methylcobalamin and a B-complex containing cyanocobalamin were effective in reducing symptoms of diabetic neuropathy, a complication of diabetes that leads to nerve damage. Additionally, many animal studies have found that each form could have neuroprotective effects and may be beneficial in treating conditions that affect your nervous system.

Conclusion

The blanket ban on methylcobalamin would soon to be revoked as it has been approved by FSSAI scientific panel as a nutraceutical ingredient. It is an essential nutrient and is required to treat vitamin B12 deficiency in people with pernicious anemia, diabetes and other disorders. Methylcobalamin aids in growth of healthy blood cells, nerve cells in the body. It is a best treatment as well as dietary supplement for the people who cannot absorb vitamin B12 and/or suffers from its deficiencies. Monotherapy of methylcobalamin improves plasma/serum homocysteine level and improve the neuropathic symptoms also. Combination therapy with other vitamin B complexes seems to be more effective. Hence, methylcobalamin may be considered as one of the promising dietary supplement and medicine having a number of potential benefits.

Methylcobalamin is widely marketed in the country as a drug for neurological disorders with a recommended dietary allowance of 2000 mcg intramuscular but according to FSSAI it is detrimental for patients when it used above 1 mcg for prevention and disease management. Industry experts pinpoint that a ban imposed on methylcobalamin warrants scrutiny in the wake of dual standards by the regulatory authorities of CDSCO and FSSAI.

Nutraceutical experts have contested that when gazette notification is talking about vitamin B12, it refers to which type of vitamin B12 as all four vitamin B12 such as methylcobalamin, cyanocobalamin, hydroxycobalamin and adenocylcobalamin are different and have different level of absorption in the human body, and therefore recommended dietary allowance and upper limit for each type of vitamin B12 must be different.

Dr Sanjay Agrawal
Leading Pharmaceutical Consultant
Editor-in Chief of IJMToday

The post Methylcobalamin (vitamin B12 ) – ban imposed warrants scrutiny appeared first on Health Vision.