Levocarnitine 500mg + Methylcobalamin 1500mcg + Folic Acid 1.5mg Tablets

Levocarnitine, Methylcobalamin and Folic acid combination for Nutritional deficiencies and Neuropathy

IntroductionŸ Adequate intake of Vitamins and nutritionally-essential minerals is required for nearly all metabolic, developmental, and

1growth processes, and for good health across the lifespan.Ÿ Peripheral neuropathic pain (PNP) leads to an unpleasant experience of patients due to lesion of peripheral nerves, which

may be a result of a complication of Diabetes mellitus, drug adverse effect or other origins.

Ÿ L-Carnitine, a quaternary amine shuttles the long-chain fatty acids into the mitochondria for their subsequent β-oxidation in the matrix (Figure 1) and to produce Adenosine triphosphate (ATP)

3as form of energy.

Figure 1. L-Carnitine function in MitochondriaCPT I-Carnitine palmitoyl transferase I, CPT II-Carnitine palmitoyl transferase II

L-Carnitine

Figure 2. The effect of L-carnitine supplementation on the quality of life of diabetic patients with muscle

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Ÿ L-Carnitine has anti-inflammatory and antioxidant properties and improves insulin sensitivity, protein

4nutrition, dyslipidemia, and membrane stability.

Ÿ L-carnitine alleviates muscle cramps and improves the Quality of Life in Diabetic patients with muscle

5cramps (Figure 2).

Table 1: Mean values and comparison between values of some electrophysiological parameters before and after treatment.

Before treatment After treatment

Right median motor distal latency (msec)amplitude (mV)NCV (m/sec)F response latency (msec)

4.35 ± 0.86.82 ± 2.649.9 ± 9.330.5 ± 7.1

4.2 ± 0.6*8.27 ± 2.6**56.3 ± 7.3*28.5 ± 2.4*

Right ulnar motor distal latencyamplitudeNCVF response latency

3.09 ± 0.478.32 ± 2.1552.1 ± 6.128.7 ± 2.6

2.72 ± 0.5*9.69 ± 1.7**55.1 ± 11*27.3 ± 2*

Right peroneal motor

distal latencyamplitudeNCVF response latency

5.0 ± 0.72.8 ± 1.539.8 ± 4.453.0 ± 6.7

4.3 ± 0.4*3.2 ± 1.7**40.2 ± 4.655.3 ± 4.7

Ÿ L-Carnitine may improve peripheral neuropathy (Table 1) and ventricular dispersion and is well-

6tolerated in patients with Diabetes.

Ÿ L-Carnitine may have an important role for prevention of muscle wasting and reducing

7the frequency of muscle cramping.

Ÿ Oral L-carnitine at a dose of 50-400 mg/kg/day divided into three doses is the primary treatment in

8Systemic Primary Carnitine deficiency.

Ÿ Methylcobalamin (MeCbl), the activated form of Vitamin B12, has been used to treat some nutritional diseases. It helps in neuronal protection promoting

9,10injured nerve and axonal regeneration.Ÿ Methylcobalamin stimulates production of S-

adenosylmethionine (SAM) and phosphatidylcholine (lecithin), which are

11Ÿ important for myelination of nerve cells (Figure 3).

Methylcobalamin

Ÿ Methylcobalamin alone or in combination with other drugs in patients with Diabetic neuropathic pain:o Alleviated neuropathic pain symptomso Improved nerve conduction velocity o Improved the symptoms of paresthesia, burning pains and heavinesso Relieved spontaneous pain by 73%o Reduced pain scores and was well-tolerated

Ÿ Methylcobalamin alone or in combination with other drugs also reduced pain in o Subacute Herpetic Neuralgiao Glossopharyngeal Neuralgia

9o Trigeminal Neuralgia

Ÿ Oral methylcobalamin 0.5 mg t.i.d. for 24 weeks was as effective as acetyl-L-carnitine 500 mg t.i.d. in patients with Diabetic 10

Peripheral Neuropathy(Table 2).

Figure 3. Vitamin B12 and the creation of the myelin sheaths

Vitamin B12

regulates

stimulates production of

lowers SAM

methylates methylates

Myelinbasic

protein

Phosphatidylcholin (Lecithin)

Cytokines

produce regenerate

stimulates production of part of creates

NervesattacksHomocysteine attacks

attack

Radicals

Methylmalonic acid

neutralises

crucial for lowers

Lipid metabolism

www.b12-vitamin.com

Methylcobalamin Adenosylcobalamin

Myelin sheaths Nerve fibres

ALC (n=117) MC ( n=115) P-value:

change

in ALC

vs MC

Baseline Week 12 Week 24 Change

from

baseline to

week 24

P-value:

baseline

vs week

24

Baseline Week 12 Week 24 Change

from

baseline to

week 24

P-value:

baseline

vs week

24

NSS+NDS 13.10– 2.80 10.50– 3.78 9.09– 4.24 4.01– 3.25 <0.0001 12.79– 2.80 10.51– 3.70 9.33– 4.34 3.46– 3.43 <0.0001 0.14

NSS 6.52– 1.52 4.95– 2.21 4.17– 2.45 2.35– 2.23 <0.0001 6.37– 1.71 4.94– 2.12 4.25– 2.60 2.11– 2.48 <0.0001 0.38

NDS 6.58– 2.19 5.55– 2.50 4.92– 2.62 1.66– 1.90 <0.0001 6.43– 2.04 5.57– 2.37 5.08– 2.41 1.35– 1.65 <0.0001 0.23

All continuous variables were presented as mean – standard deviation. All comparisons were analyzed byt-test. ALC, acetyl-L-carnitine; MC, methyl-cobalamin; NDS, neuropathy disabilityscore; NSS, neuropathy symptom score.

Table 2: Changes in the neuropathy symptom score, the neuropathy disability score, and the sum of both comparing baseline and week 12 and week 24 in the full analysis set population

Ÿ Oral Methylcobalamin 1500 μg/day significantly improved the symptoms of neuropathy in 37 subjects

12 with Diabetic Polyneuropathy (DPN; Table 3).

Table 3: Change in the rating of individual items of the Toronto CSS score comparing baseline and post treatment.

Symptom rating post treatment

Foot

Pain 01

Tingling 0 1

Weakness 0 1

Symptom rating at baseline 0* N (%)

23 (88.5) 3 (11.5)

9 (90.0) 1 (10.0)

20 (87.0) 3 (13.0)

Symptom rating atbaseline 1* N (%)

7 (63.6) 4 (36.6)

14 (51.8) 13 (48.2)

9 (64.3) 5 (35.7)

p-value*

0.08

0.03

0.10

Ÿ Folic acid, natural form of Vitamin B9, plays a key role in the growth, differentiation and regeneration of the central nervous system.

13Ÿ Folic acid is also good for peripheral nerve repair (Figure 4).

Folic acid

Figure 4.Folic acid promotes peripheral nerve injury repair by Schwann cell proliferation, migration, and secretion of nerve growth factor (NGF)

Ÿ Folate deficiency is a risk factor for peripheral neuropathy among patients 14

younger <40 years of age.Ÿ Supplementation with 1 mg of folic acid for 16 weeks may be useful for

15enhancing nerve conduction velocity in diabetic polyneuropathy patients.

Ÿ Periconceptional folic acid reduces Neural Tube Defects (NTDs) by 72-16

100%.Ÿ The American Academy of Pediatrics recommends that all women capable of

17 becoming pregnant consume 400 µg of folic acid daily to prevent NTDs.

Peripheral neuropathy events, age 18-40 years

Folate <6.8 Folate 6.8-13.5 Folate >13.6

0.0100

0.0075

0.0050

0.0025

0.0000

0 1000 2000 3000 4000Time (days)

Cum

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ive

even

t

Cum

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Figure 5.Cumulative event curves for peripheral neuropathy according to serum folate concentrations

Folic acid NGF Secretion

Schwann cells

Migration

Promotes

Folic acid promotes peripheral nerve injury repairby affecting Schwann cell function

61/C, 6th Main Road, 4th Phase, 7th Block, B.S.K 3rd Stage, Bangalore - 560085.

2020

Indications As a nutritional supplement in Ÿ Peripheral neuropathy Ÿ Diabetic polyneuropathy Ÿ Neuralgic pain Ÿ Carnitine deficiencyŸ Folate deficiency

Dosage One tablet daily or as advised by the Physician

Summary Available clinical evidence shows that Levocarnitine, Methylcobalamin and Folic Acid may present as an excellent combination in treating nutritional deficiencies like Peripheral neuropathy, Neuralgia, Carnitine deficiency, Folate deficiency etc.

References: 1. 2. 3. 4. 5.Blumberg JB et al. Nutrients. 2017;9(8):849. Li S et al. PLoS ONE.2015; 10(3): e0119479. Fielding R et al. Nutrients. 2018;10(3):349. Bene J et al. Nutr Diabetes. 2018;8(1):8. Imbe A et al. Endocr J. 2018 May 28;65(5):521-526. Ulvi H et al., Turk J Med Sci. 2010;40(2):169-175. Hiraoka A et al. Eur J Gastroenterol Hepatol. 2019;31(7):878-884. Magoulas PL et al. 6. 7. 8.Orphanet J Rare Dis. 2012;7:68. Zhang M et al. Neural Plast. 2013;2013:424651. Li S et al. J Diabetes Investig. 2016;7(5):777-785. Schweikart. Accessed from website 9. 10. 11.https://www.b12-vitamin.com/nerves/ as on 28.02.2020. Dominguez JC et al. Journal of Diabetes Mellitus.2012; 2:408-412. Kang et al. Neural Regen Res. 2019;14(1):132-139. 12. 13. 14. 15. 16. 17.Taverner Tet al. Nutrients. 2019;11(10):2443. Mottaghi T et al. Neurol Res. 2019;41(4):364-368. Lamers Y et al. Am J Clin Nutr. 2006;84(1):156-161. No authors listed. Pediatrics. 1999;104(2 Pt 1):325-7.

Levocarnitine 500mg + Methylcobalamin 1500mcg + Folic Acid 1.5mg Tablets