What Is Vitamin D
Vitamin D serves many purposes within the body, and you can get it from several different sources. The main function of vitamin D is to promote calcium absorption in your body.
You can get vitamin D through your diet and by getting out in the sun, as long as you dont have sunscreen on. Sunscreens block the skins absorption of the vitamin.
In both cases, the vitamin undergoes several changes within the body before its put to use. From there, vitamin D can help:
- keep your bones healthy
Cholesterol is another necessary substance in the human body. But too much of it can be a bad thing.
There are two main types of cholesterol: LDL, which we mentioned previously, and high-density lipoprotein .
HDL is commonly referred to as good cholesterol, and you want to keep HDL levels above 60 milligrams/dL.
LDL, on the other hand, is known as bad cholesterol, which is the type of cholesterol that can clot your arteries and increase your risk for heart disease and stroke. You should keep your LDL levels below 100 milligrams/dL.
B12 Deficiency Induces Expression Of Cholesterol Biosynthesis Genes In Human Adipose Tissue
The prevalence of serum B12 deficiency in this cohort of pregnant women at the time of delivery was 39.6%. Low B12 mothers had significantly higher BMI, cholesterol, LDL cholesterol, triglycerides, and homocysteine than normal B12 mothers . To validate the findings from our cultured primary human adipocytes, we further performed the key experiments in maternal subcutaneous adipose tissue chosen from normal B12 and low B12 mothers. We observed that the mRNA expressions of cholesterol regulatory genes SREBF1, SREBF2 and LDLR , and cholesterol biosynthetic gene and HMGCR were upregulated in adipose tissue from low B12 mothers compared to normal B12 mothers .
Dna Methylation And Regulation Of Lipid Metabolism Through Low B12
Methylation generally involves the process of transferring a methyl group to substrates such as enzymes, proteins, amino acids and DNA in diverse cells and tissues . In the process, guanine is normally bound with 5-methylcytosine following its development from cytosine . Usually, hypermethylation of global DNA and 5â²-cytosine-phosphate-guanineâ3â² islands located within the promoters of genes involved in lipid synthesis, accounts for the stability of the genome and silencing of the lipogenic genes, respectively . This is greatly dependent on the availability and sufficiency of SAM synthesized with the aid of methyl donors such as B12 and folate . Low B12 independently impairs the MS action affecting SAM/SAH ratio which is a principal determinant of the methylation potential of cellular DNA, thereby inducing dysregulation of gene expressions . Demethylation associated with DNA of the genome, persists as one of the earliest evidences of epigenetic modifications triggered by diets deficient in methyl donors, contributing to hepatocarcinogenesis in animals .
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Culture And Differentiation Of Human Pre
Human preadipocyte cell line Chub-S7 and human primary preadipocytes were cultured and differentiated as described elsewhere . Briefly, the preadipocytes were grown to confluence in customised growth media . At confluence , preadipocytes were differentiated in differentiation media for 72 h and were maintained in nutrition media thereafter for 11 days . The day differentiation was initiated was considered as day 0. On day 14, conditioned media were collected and cells were harvested for protein and RNA analysis and stored at 80°C until use. Primary human preadipocytes were isolated from human abdominal subcutaneous AT, collected from patients undergoing surgery with informed consent obtained in accordance with LREC guidelines and with ethics committee approval.
The DMEM/F-12 medium used above was customised initially for 12 different B12 and folic acid concentrations but we will present three main conditions as follows: control: normal B12 LB: low B12 and NoB: no B12 and 6 M folic acid. For methylation inhibition, preadipocytes were incubated with 200 nM of 5-aza-2-deoxycytidine at 50% confluency for 72 h and were differentiated at confluence.
Evidence From Clinical 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. As previously stated, the term âlow B12â in all clinical evidence reported in this review refers to plasma/serum B12 levels â¤120â300 pmol/L .
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Effect Of Vitamin B12 Deficiency On Gestational Outcome
Severely deficient B12R+ mice showed very poor gestational outcome as compared to both control and moderately deficient B12Râ mice. There was around 35% weight gain during pregnancy in the B12R+ mice as compared to approximately 51 and 47% in control and B12Râ mice, respectively. There was delayed conception in B12R+ mice and the percentage of successful conception in B12R+ was half of that observed in the control and B12Râ mice. The litter size was very low in case of severe deficiency as compared to 8 and 7 in control and B12Râ mice, respectively. The body weight and body length at birth were significantly lower in pups of both the severe and moderately deficient dams clearly indicating that these pups were small for gestational age. A high percentage of pups born to B12R+ dams died during lactation period compared to both control and B12Râ dams. The body weight of pups from B12R+ mothers remained significantly lower even at weaning as compared to those born to control and B12Râ dams .
Table 5. Gestational outcome.
How Vitamin B12 Deficiency Harms Health
In the body, vitamin B12 also known as cobalamin is especially vital to making red blood cells, and maintaining proper function of nerve cells. When vitamin B12 levels are low, a person can develop health problems related to red blood cells and nerve cells malfunctioning.
The most common problems related to low vitamin B12 levels include:
- Anemia. This means the red blood cell count is low. Red blood cells carry oxygen in the blood, so anemia can cause fatigue or shortness of breath. The breakdown of faulty red blood cells can also cause jaundice.
- Neuropathy. This means that nerves in the body are not working well. This can cause a variety of symptoms, including tingling, numbness, burning, poor balance, and walking difficulties.
- Cognitive impairment. This means that nerve cells in the brain are not working well. This can cause memory problems, irritability, and even dementia.
You may have heard that vitamin B12 deficiency can cause pernicious anemia. But in fact, the term pernicious anemia means a specific vitamin B12 deficiency caused by the loss of a bodys ability to make intrinsic factor. The body needs intrinsic factor to absorb vitamin B12 without it, vitamin B12 levels eventually drop. This often causes anemia, but sometimes symptoms of nerve and brain problems occur first.
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Srebf1 And Ldlr Genes Are Hypomethylated In Low Vitamin B12 Condition
Vitamin B12 plays an important role in regulating AdoMet levels which has been shown to regulate the SREBF1 expression . AdoMet is the methyl donor and is responsible for methylation of DNA, protein, and lipids we hypothesised that the upregulation of cholesterol synthesis in low B12 conditions could be due to altered methylation of genes regulating cholesterol biosynthesis. Therefore, we interrogated data from our genome-wide study to generate quantitative levels of DNA methylation at SREBF1, SREBF2, and LDLR.
Effect of vitamin B12on methylation of cholesterol regulatory genes. Genome-wide DNA methylation analysis of cholesterol regulatory genes was performed in adipocytes cultured in customised media, control, LB, and NoB. SREBF-1 and LDLR from Illumina. Validation by BS-pyrosequencing was also done in the same samples and methylation status confirmed for SREBF-1 and LDLR. All experiments were performed as triplicates. Values are mean±SEM. *P0.05 **P0.01, ***P0.001, P value compared to control.
Effect Of Vitamin B12 Restriction On Plasma Vitamin B12 And Homocysteine Levels After 12 Weeks Of Feeding
After 12 weeks of feeding different experimental diets, we observed significantly decreased levels of vitamin B12 in both B12R+ and B12Râ mice as compared to control mice . The plasma homocysteine was also significantly high in both B12R+ and B12Râ as compared to the control mice. However, there were no changes in the plasma folate levels between the groups.
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The Best Foods To Increase B12 Status
Food is hands down the best way to restore adequate and optimal vitamin B12 status. Often, low B12 status reveals a diet that is lacking in animal protein and thus nutrient density. Prioritizing animal protein – in particular darker cuts of meat and organ meats – is crucial for correcting the root cause of most insufficiencies and deficiencies. Traditional diets are a great foundation for correcting low B12, try adding more of the following to your nutritional arsenal
clams – 49mcg
beef – 3.0mcg
eggs – 1.3mcg
Aim for 2-5 servings per day of these nutrient-dense foods, depending on your level of deficiency and activity.
Why Do I Need Vitamin B12
Vitamin B12, biochemical name cobalamin, is an essential B-vitamin that helps to convert the carbs you eat into fuel. In fact, b-vitamins work as a team and also help to metabolize proteins and fats .
Vitamin B12 is particularly important for your nervous system, producing RNA and DNA for growth and repair, methylation pathways, red blood cell production , and much more.
Vitamin B12 teams up with folate and vitamin B6 to metabolize homocysteine in the body, where high levels are associated with inflammation and increased risk of heart disease. It also plays a role in melatonin production, the circadian hormone that helps to initiate sleep so you can recover effectively.
Common symptoms of low B12 include fatigue, shortness of breath, weakness, as well as anxiousness, poor sleep, inability to concentrate, subpar memory, loose stools, numbness and tingling sensations in your toes and fingers.
Let’s take a look at who might be at risk of low vitamin B12 levels.
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Body Composition Analysis By Dual Energy X
The body composition of mice from each group was monitored after 4 weeks and 12 weeks of feeding their respective diets by using DEXA . Adiposity index , an index of visceral adiposity, was calculated following the method of Taylor and Philips . Briefly, three major fat pads were quickly dissected at the end of 12 weeks of feeding and their wet weights were recorded.
High Activity High Stress
Are you training intensely for an event or competitive season? Are you really busy and on the go with work and/or kids at home? The greater stress load on your body, the greater the demand for vitamin B12 which can put drain your levels, especially when combined with a diet that doesn’t contain enough of the essential vitamin.
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Vitamin B3 Niacin For Lowering Cholesterol
Niacin works in the liver by affecting the production of blood fats, and it has been well-researched. Several well-designed double-blind, placebo controlled studies have found that niacin can reduce LDL cholesterol by approximately 10 percent and triglycerides by 25 percent while raising HDL cholesterol by 20 percent to 30 percent.
High LDLs lead to atherosclerosis and then cardiovascular disease, warns Nadia Chariff, Health Advisor & Registered Dietitian at Coffeeble. Make no mistake, dietary & lifestyle factors such as high saturated fat intake & lack of exercise definitely play a part! Besides recommending alternative diets & increased activity, I recommend niacin to my patients.
Supplement A Healthy Lifestyle
Heart disease is a significant concern for Americans. Living a healthy lifestyle, exercising regularly, and supplementing a nutritious diet with certain vitamins and herbs can help to lower cholesterol and improve heart health. Speak with a healthcare provider or pharmacist to find out what heart health supplements are best.
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Analytical Determinations For Clinical Study
Serum, HDL and LDL cholesterol, and triglycerides were determined using an auto analyzer Synchron CX7 based on enzymatic colorimetric assays. B12 and folate were determined by electrochemiluminescent immunoassay using a Roche Cobas immunoassay analyzer. The reference values in our laboratory for non-pregnant women are as follows: 191 to 663 ng/L for vitamin B12 and 4.6 to 18.7 g/L for folate.
Does Low B12 Affect Cholesterol
Specifically, we have demonstrated that low vitamin B12 is associated and independently predicted higher total cholesterol, LDL cholesterol, and cholesterol-to-HDL ratio in serum induced cholesterol biosynthesis and homocysteine in adipocytes increased expression of SREBPs and genes responsible for
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The Link Between Vitamin B12 Deficiency And Stroke
Vitamin B12 deficiency is one of the lesser-known factors that can contribute to stroke risk. Vitamin B12 is an important nutrient found in several types of food. Nutritional deficiency has long been known to cause health problems, particularly in children and pregnant women. It turns out that not getting enough vitamin B12 can contribute to stroke among people of all ages, and it can lead to an increased risk of stroke among children and pregnant women as well.
The link between vitamin B12 deficiency and stroke involves a multi-step process.
Nutritional deficiencies of folic acid, B vitamins, and especially vitamin B12, cause an increase of a chemical called homocysteine. Excessive homocysteine creates two problems one of these problems is inflammation of the blood vessels and the other problem is a process called oxidative stress.
Inflammation is a major contributor to stroke. Inflammation is the buildup of white blood cells that are intended to fight infection. But the unnecessary inflammation that is associated with vitamin B12 deficiency results in damage to the blood vessels and excess deposits inside the blood vessels. This buildup can ultimately lead to interruption of normal blood flow in the brain which is a stroke.
Therefore, vitamin B12 deficiency can be the culprit in a cascade of stroke-inducing physiological events.
Effect Of Vitamin B12 In Primary Human Adipocytes
In order to validate the findings from human adipocyte cell line ChubS-7, the key experiments were also performed in cultured primary human adipocytes under the same conditions. The total cholesterol as well as homocysteine was significantly increased in primary adipocytes in the LB and NoB conditions compared with control . The mRNA expressions of genes regulating cholesterol biosynthesis, SREBF1 and SREBF2, and LDLR were also significantly increased .
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Neural Tube Defects And Folic Acid
As with a vitamin B12 deficiency, a lack of folate can also affect an unborn baby’s growth and development in the womb .
This increases the risk of neural tube defects, such as spina bifida, developing in the unborn baby.
It’s recommended that all women who could get pregnant should take a daily supplement of folic acid.
You should take a 400 microgram supplement of folic acid every day before you get pregnant, and up until you’re 12 weeks pregnant.
Page last reviewed: 23 May 2019 Next review due: 23 May 2022
Establishing A Mouse Model For Vitamin B12 Deficiency
After 4 weeks of feeding the respective diets to weanling female C57BL/6 mice, we measured the levels of vitamin B12 and homocysteine in their plasma. Concentration of vitamin B12 in the plasma of B12R+ and B12Râ mice was significantly lower than that of control mice. As expected, among the B12-restricted groups, B12R+ mice had lower plasma vitamin B12 concentrations than B12Râ mice, showing severe deficiency. On the other hand, plasma homocysteine levels were significantly higher in both the restricted groups as compared to control . In line with their lowest plasma vitamin B12 levels, the plasma homocysteine levels were the highest in B12R+ mice. The levels of folate were comparable among all the three study groups. In line with available literature, dietary fiber pectin inhibited vitamin B12 absorption and led to severe deficiency in B12R+ mice. On the other hand, dietary fiber cellulose did not interfere with vitamin B12 absorption and the B12Râ mice developed moderate deficiency. Thus, 4 weeks of feeding vitamin B12-restricted AIN-76A diet with different dietary fibers pectin and cellulose to weanling C57BL/6 mice successfully established severe and moderate vitamin B12-deficient mouse models, respectively.
Table 1. Plasma vitamin B12, folate, and homocysteine levels after 4 and 12 weeks of feeding.
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Low Vitamin B12 Induces Expression Of Cholesterol Synthesis And Transport Regulators
The sterol regulatory element-binding protein transcription factors and LDLR play a critical role in regulating cholesterol quantity. Protein as well as mRNA expressions of both SREBPs was significantly upregulated in NoB and LB conditions compared with control . The LDLR mRNA expression was also significantly higher in LB and NoB conditions compared with control . The mRNA expression of other regulatory genes insulin induced gene 1 and StAR-related lipid transfer protein 4 was also significantly upregulated in both NoB and LB conditions compared to control .
Effect of vitamin B12on regulation of cholesterol biosynthesis. Protein and/or mRNA expression of genes regulating cholesterol biosynthesis in adipocytes. SREBP-1, SREBP-2, SREBF1 and SREBF2, LDLR, INSIG1 and StarD4. All experiments were performed as triplicates. Values are mean±SEM. *P0.05 **P0.01, ***P0.001, P value compared to control.
Diabetic Neuropathy And B
Diabetic neuropathy can also affect other body parts, including the gastrointestinal tract.
You dont have to have diabetes to develop neuropathy. Prolonged B-12 deficiency can also damage your nerves.
Whether you have diabetes or not, symptoms of neuropathy should not be ignored.
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