Obesity has become a global epidemic, contributing to a significant percentage of worldwide mortality and elevating the risks of metabolic disorders such as type 2 diabetes, hypertension, and cardiovascular diseases. This has led to increased public health concerns. Vitamin B12, also known as cobalamin, is a water-soluble vitamin crucial for various bodily functions. It is naturally present in many foods, including meat, fish, and dairy products, and is also available as a dietary supplement. While some propose that vitamin B12 can boost energy and endurance during exercise, the scientific evidence supporting this claim remains limited. This article explores the relationship between vitamin B12 and weight loss, examining the evidence from preclinical and clinical studies.
What is Vitamin B12?
Vitamin B12 is an essential vitamin that the body cannot produce on its own, making it crucial to obtain it through diet or supplementation. It plays a vital role in DNA synthesis, red blood cell formation, and maintaining healthy brain function. B12 is predominantly found in animal products, such as meat, eggs, and milk, although traces can be found in some algae.
The Role of Vitamin B12 in the Body
B12 (cobalamin) is classified as an essential vitamin as it is entirely obtained from the diet. It is also synthesized naturally by some large intestine-resident bacteria in humans The vitamin is uniquely composed of a central cobalt atom linked to six ligands, with four of the latter structurally reduced to form a corrin ring that connects and encircles the former through direct nitrogen linkages. Directly below the central cobalt is an α-axial 5,6-dimethylbenzimidazole (DMB) ligand which, through a phosphoribosyl moiety, links to the corrin ring and confers a high specificity on the vitamin for intrinsic factor (IF) binding in the lower gastrointestinal tract. The β-axial ligand (R-ligand), positioned above the corrin ring, may differ in diverse forms such as methyl, 5′-deoxyadenosyl, hydroxo, acquo or cyano groups.
Once absorbed, vitamin B12 undergoes processing into key cytosolic (MeCbl) and mitochondrial (AdoCbl) co-enzyme forms. These forms participate in crucial metabolic pathways.
Vitamin B12 Deficiency
There is no international consensus on the lower limit of B12 to define B12 deficiency in adults and pregnancy. But there is some agreement that it should be between 120 and 220 pmol/L (higher threshold in pregnancy) with the upper limit between 650 and 850 pmol/L. Other parameters, such as holo-TC, methyl malonic acid (MMA) and homocysteine (tHcy), are better markers of tissue level B12 deficiency, especially when the serum B12 levels are borderline (150-220 pmol/L).
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Vitamin B12 deficiency can arise from various factors, including:
- Reduced B12 Intake: Malnutrition, vegetarian diets, and alcohol abuse can contribute to inadequate B12 intake.
- Malabsorption: Conditions like atrophic gastritis, bariatric surgery, celiac disease, Crohn's disease, and ileal resection can impair B12 absorption.
- Medications: Certain drugs, such as metformin and proton pump inhibitors, can interfere with B12 absorption.
- Deficiency in Transcobalamin (TC): Transcobalamin is a protein crucial for transporting B12 in the blood. Deficiency in TC can lead to B12 deficiency.
The risk of developing B12 deficiency is higher in vegetarian populations such as in India. However, it is not uncommon in other populations, ranging between 10 and 30%. And is higher in pregnant populations.
Vitamin B12 and Lipid Metabolism: Pre-clinical Evidence
Pre-clinical studies using animal models have demonstrated the effect of low B12 on cardiometabolic risk.
A study in adult Wistar rats that were fed a B12 restricted diet (control−0.010 mg/kg B12 vs. B12 restricted-0.006 mg/kg B12) during maternal or postnatal period, predicted higher visceral adiposity and resulted in alteration in the metabolism of lipids in the offspring. Low plasma B12 (277 pg/mL B12) resulting from B12-restricted diet or a combination of B12- and B9-restricted diet (219 pg/mL B12) for a period of three months in pre-pregnant Wistar rats resulted in increased body weight compared to control (1164 pg/mL B12). B12-deficient rats had increased total body fat whereas B9-deficient rats presented with elevation in visceral fat mass. Likewise, in female C57 BL/6 mice, severe decrease in plasma B12 (138 pg/mL), but not moderate (208 pg/mL) (compared to 406 pg/mL control B12) was reported to induce higher adiposity and altered lipid profile in their offspring.
Restriction of maternal B12/folate/methionine (control vs. restricted: B12 (1000.5 pM vs. 198 pM), folate (6.90 nM vs. 4.42 nM), methionine (39.1 µM vs. 30.8 µM)) at the stage of conception in sheep models, showed increased resistance to insulin and elevated blood pressure in its offspring. In addition, the adult male offspring had higher adiposity and altered functioning of their immunity. This evidence was explained by the observation of male-specific demethylation of the affected loci, therefore, providing convincing reasons for the these differences observed in the phenotypes of the offspring. Finally, the study concluded that the decreased methylation of DNA could be explained by lower availability of s-adenosyl methionine (SAM), a well-known methyl donor, which is crucial in epigenetic modulations underlying the development of resistance to insulin.
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Mother Wistar rats with low plasma B12 (277 pg/mL B12 compared to 1164 pg/mL control) produced offspring which had increased levels of adiposity, triglycerides (TG) and total cholesterol as well as decreased leptin and adiponectin, compared to control offspring, showing a dysregulated metabolism of lipids. C57 BL/6 mice with deficient plasma B12 levels at 12 weeks (145 pg/mL vs. 548 pg/mL control) and 36 weeks (123 pg/mL vs. 522 pg/mL control) had increased plasma TG, cholesterol and pro-inflammatory markers comprising tumor necrosis factor-alpha (TNFα), interleukin−1 b, interleukin−6, as well as lower adiponectin concentrations. B12 deficiency inhibited beta oxidation of fatty acids and lipolysis in hepatic tissues of rat offspring born to B12 deficient mothers (227 pg/mL B12 vs. 1164 gp/mL control). However, in these studies, B12 supplementation during parturition resulted in the restoration of both pathways. In a recent study, targeting the elucidation of the cellular mechanism induced by low B12 in human adipocyte cell line (Chub-S7 (0.15 nM compared to 500 nM control)), elevated levels of cholesterol and TG were observed in low B12 cells compared with controls. This was explained by a reduction in the methylation potential and the SAM: SAH ratio in low B12 conditions. Validation of the above findings was further endorsed in primary human adipocyte models, demonstrating that B12-deficient primary human adipocytes had significantly elevated levels of total cholesterol, tHcy and mRNA expression of key genes that regulate the biosynthesis cholesterol, as compared to controls.
Adult male Sprague-Dawley rat model treated with testosterone enanthate (0.5 mg/100 gm) and B12 (500 µg/kg) demonstrated significant changes with peripheral cortisol and association with vascular dysfunction. Another study involving four-weeks simultaneous therapy with 10 mg/kg folate and 500 µg/kg B12 in Wistar rats, aiming to assess the effect of B12 and folate supplementation on myocardial infarction (MI) in rats presenting with hyperhomocysteinemia, there was a significant reduction in the elevated heart rate and blood pressure as well as attenuation of severe cardiac histopathological alterations. The study suggested that aggravation of MI risk might result from hyperhomocysteinemia, however, B12 and/or folate administration may reduce MI risk and tHcy levels, accounting for reduced harmful consequences associated with hyperhomocysteinemia.
Vitamin B12 and Weight Loss: Human Studies
Most observational and epidemiological evidence on the effects of B12 on metabolic risk are from an Asian population but there are few studies in Western populations. An association between maternal body mass index (BMI) at early stage pregnancy and plasma B12 and/or B9, in a recent cross-sectional study, was observed in obese women compared to women with normal BMI.
While several studies suggest a potential link between vitamin B12 and weight management, the evidence remains inconclusive. Some studies have found that individuals with higher B12 levels are less likely to be obese, while others have shown that low B12 levels are associated with a higher risk of overweight or obesity. However, these studies only demonstrate an association and do not prove that B12 directly causes weight loss.
Vitamin B12 Injections and Weight Loss
Vitamin B12 injections have gained popularity as a potential weight loss aid. These injections deliver a concentrated dose of vitamin B12 directly into the bloodstream, bypassing the digestive system and ensuring optimal absorption.
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The rationale behind using B12 injections for weight loss is based on the vitamin's role in metabolism and energy production. B12 helps convert fats and proteins into energy, potentially increasing metabolic rate and promoting fat burning. Additionally, B12 injections can boost energy levels, combating fatigue and enabling individuals to engage in more physical activity.
However, it's important to note that B12 injections are not a magic bullet for weight loss. They are most effective when combined with a healthy lifestyle that includes a balanced diet and regular exercise.
Sources of Vitamin B12
Vitamin B12 is naturally found in animal products, including:
- Meat
- Fish
- Poultry
- Eggs
- Milk and milk products
It is also added to fortified foods, such as:
- Breakfast cereals
- Plant-based milk (almond, soy, or hemp milk)
Vitamin B12 supplements are available in various forms, including:
- Tablets
- Capsules
- Liquids
- Lozenges
Individuals who do not regularly consume animal products may consider adding fortified foods to their diet or taking a supplement to ensure adequate B12 intake.
Potential Benefits of Vitamin B12
Beyond its potential role in weight management, vitamin B12 offers several other health benefits:
- Improved Energy Levels: B12 helps convert food into energy, reducing fatigue and increasing overall energy levels.
- Enhanced Brain Function: B12 is essential for cognitive function and memory.
- Healthy Red Blood Cell Formation: B12 is required for the production of red blood cells, preventing megaloblastic anemia.
- Nervous System Support: B12 helps maintain the health of the nervous system.