How much vitamin B12 is too much. What are the potential side effects of excessive B12 supplementation. Is it necessary to take B12 supplements if you have a balanced diet. How can you ensure adequate B12 intake without risking overconsumption.

The Importance of Vitamin B12 in Human Health

Vitamin B12 plays a crucial role in numerous bodily functions, making it an essential nutrient for overall health. This water-soluble vitamin is responsible for:

• Red blood cell formation
• Energy production
• DNA synthesis
• Nerve maintenance

While B12 is naturally present in many animal-based foods, some individuals may struggle to obtain sufficient amounts through diet alone. Factors that can increase the risk of B12 deficiency include:

• Inflammatory bowel disease (IBD)
• Certain medications
• Genetic mutations
• Advanced age
• Dietary restrictions (e.g., vegan or vegetarian diets)

Given its importance, it’s crucial to maintain adequate B12 levels. But how much is enough, and is there such a thing as too much B12?

Understanding B12 Deficiency and Its Consequences

B12 deficiency can lead to severe health complications if left untreated. Some of the most common symptoms include:

• Nerve damage
• Anemia
• Chronic fatigue
• Cognitive decline

Individuals at risk of B12 deficiency should consult their healthcare provider about incorporating a high-quality B12 supplement into their diet. However, it’s essential to understand that not everyone requires supplementation.

Do Healthy Individuals Need B12 Supplements?

Current evidence suggests that people who consume adequate amounts of B12-rich foods and can properly absorb and utilize this nutrient may not need to supplement. A 2021 meta-analysis found that B12 supplementation is likely ineffective for improving cognitive function and depressive symptoms in patients without advanced neurological disorders.

The Upper Limit of B12 Intake: How Much Is Too Much?

Interestingly, no Tolerable Upper Intake Level (UL) has been established for B12 due to its low toxicity level. The body typically excretes excess B12 through urine, making it generally safe even at high doses. However, this doesn’t mean that excessive supplementation is without risks.

Potential Side Effects of High-Dose B12 Supplementation

While rare, some studies have linked megadoses of B12 to adverse effects:

• Acne outbreaks
• Rosacea flare-ups
• Potential complications in individuals with diabetes or kidney disease
• Possible increased risk of autism spectrum disorder in unborn children when pregnant women take extremely high doses

It’s important to note that many of these studies focused on high-dose injections rather than oral supplements, and more research is needed to confirm these findings.

Recommended B12 Intake: Finding the Right Balance

The recommended daily intake (RDI) of vitamin B12 is 2.4 mcg for both men and women, with slightly higher needs for pregnant and breastfeeding women. However, when treating B12 deficiency, daily oral supplements of up to 2 mg (2,000 mcg) have been found safe and effective.

Natural Sources of Vitamin B12

For individuals not at risk of B12 deficiency, a well-rounded diet should provide sufficient B12. Rich food sources include:

• Eggs
• Red meat
• Poultry
• Seafood
• Milk and dairy products
• Fortified cereals
• Nutritional yeast
• Fortified non-dairy milk

The Role of B12 in Energy Production: Separating Fact from Fiction

B12 supplements are often marketed as energy boosters, but is there truth to this claim? While B12 plays a crucial role in energy metabolism, there’s currently no evidence suggesting that additional B12 increases energy levels in people with adequate stores of this vitamin.

However, individuals with B12 deficiency may experience increased energy levels upon supplementation, as addressing the deficiency can improve overall metabolic function. It’s important to distinguish between addressing a deficiency and seeking benefits beyond normal physiological needs.

The Energy Myth: Why More Isn’t Always Better

The misconception that more B12 equals more energy has led some individuals to consume megadoses of this vitamin. However, once the body’s B12 needs are met, additional intake doesn’t provide extra benefits. In fact, excessive supplementation may lead to unnecessary side effects or mask underlying health issues.

B12 Supplementation and Cognitive Function: What Does the Research Say?

The relationship between B12 and cognitive function has been a subject of extensive research. While B12 deficiency can certainly impact cognitive performance, the benefits of supplementation for those with adequate levels are less clear.

B12 and Depression: Examining the Link

Some studies have suggested a potential link between B12 deficiency and depression. However, the 2021 meta-analysis mentioned earlier found that B12 supplementation was likely ineffective for improving depressive symptoms in individuals without advanced neurological disorders. This highlights the importance of addressing B12 deficiency when present, but also cautions against expecting mood-boosting effects from supplementation in those with normal B12 levels.

Special Considerations: B12 Supplementation in Specific Populations

While B12 supplementation is generally safe, certain groups may need to exercise caution or seek medical advice before starting a supplement regimen.

B12 and Diabetes: A Complex Relationship

A 2010 study found that people with diabetic nephropathy experienced a more rapid decline in kidney function when supplemented with high-dose B vitamins, including 1 mg per day of B12. Furthermore, these participants had a greater risk of heart attack, stroke, and death compared to those receiving a placebo. While more recent studies are needed to confirm these findings, individuals with diabetes should consult their healthcare provider before starting high-dose B12 supplementation.

Pregnancy and B12: Striking the Right Balance

Adequate B12 intake is crucial during pregnancy for fetal development. However, one study suggested that extremely high B12 levels due to vitamin supplements might increase the risk of autism spectrum disorder in the unborn child. This underscores the importance of following recommended intake levels and consulting with a healthcare provider for personalized advice during pregnancy.

Absorption Challenges: When Supplementation Becomes Necessary

While a balanced diet can provide sufficient B12 for many people, certain conditions can impair B12 absorption, necessitating supplementation. These include:

• Pernicious anemia
• Atrophic gastritis
• Celiac disease
• Crohn’s disease
• Surgical procedures affecting the stomach or small intestine

In these cases, healthcare providers may recommend oral supplements, sublingual tablets, or B12 injections to ensure adequate intake.

The Aging Factor: B12 Absorption in Older Adults

As we age, our ability to absorb B12 from food sources may decrease. This is primarily due to a reduction in stomach acid production, which is necessary for B12 absorption. Consequently, adults over 50 are often advised to meet their B12 needs through fortified foods or supplements.

Monitoring B12 Levels: The Importance of Regular Check-ups

Given the potential risks of both deficiency and excessive intake, regular monitoring of B12 levels is crucial, especially for individuals in high-risk groups. Blood tests can accurately measure B12 levels, helping healthcare providers determine whether supplementation is necessary and at what dosage.

Beyond Blood Tests: Recognizing the Signs of B12 Imbalance

While blood tests are the most accurate way to assess B12 status, being aware of potential symptoms of deficiency or excess can be helpful. Symptoms of B12 deficiency may include:

• Fatigue
• Weakness
• Shortness of breath
• Numbness or tingling in extremities
• Memory problems
• Mood changes

On the other hand, potential signs of excessive B12 intake might include:

• Acne or rosacea flare-ups
• Headaches
• Nausea
• Dizziness

If you experience any of these symptoms, it’s important to consult with a healthcare provider for proper evaluation and guidance.

The Future of B12 Research: Emerging Trends and Potential Applications

As our understanding of vitamin B12’s role in human health continues to evolve, researchers are exploring new potential applications and refining our knowledge of optimal intake levels. Some areas of ongoing research include:

B12 and Neurological Health

While the link between B12 and cognitive function is well-established, researchers are delving deeper into its potential role in preventing or managing neurological disorders. Studies are investigating the potential benefits of B12 supplementation in conditions such as Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis.

Personalized Nutrition: Tailoring B12 Intake to Individual Needs

As the field of nutrigenomics advances, researchers are exploring how genetic variations might influence an individual’s B12 requirements and absorption capabilities. This could lead to more personalized recommendations for B12 intake based on genetic profiles.

Novel Delivery Methods

Scientists are continually working on developing new and more effective ways to deliver B12, especially for individuals with absorption issues. This includes improved sublingual formulations, transdermal patches, and even nasal sprays.

As research in these areas progresses, our understanding of optimal B12 intake and its wide-ranging health effects will undoubtedly become more nuanced and comprehensive.

How Much Vitamin B12 Is Too Much?

This essential vitamin is generally considered safe, even at high doses. However, most people get enough B12 through diet alone, and unnecessary supplementing may lead to negative side effects.

Vitamin B12 is a water-soluble nutrient that plays many critical roles in your body.

Some people think that taking high doses of B12 — rather than the recommended intake — is best for their health.

This practice has led many to wonder how much of this vitamin is too much.

This article examines the health benefits, as well as potential risks of taking megadoses of B12.

There’s no question that vitamin B12 is essential for health.

It’s responsible for numerous functions in your body, including red blood cell formation, energy production, DNA formation, and nerve maintenance (1).

Though B12 is found in many foods, such as meat, poultry, seafood, eggs, dairy products, and fortified cereals, many people don’t get enough of this important vitamin.

Health conditions such as inflammatory bowel disease (IBD), certain medications, genetic mutations, age, and dietary restrictions can all contribute to an increased need for B12.

Vitamin B12 deficiency can lead to serious complications such as nerve damage, anemia, and fatigue, which is why those at risk should talk with their doctor about adding a high quality B12 supplement to their diet (2).

Current evidence suggests that people who consume adequate amounts of B12-rich foods and are able to properly absorb and use this nutrient don’t necessarily need to supplement.

For example, a meta-analysis from 2021 found that Vitamin B12 supplementation is likely ineffective for improving cognitive function and depressive symptoms in patients without advanced neurological disorders (3).

Although B12 supplements are commonly taken to boost energy levels, there is currently no evidence suggesting that more B12 increases energy in people with adequate levels of this vitamin.

However, B12 supplements will most likely increase energy levels in those who are deficient, as this nutrient plays an important role in converting food into energy.

Summary

B12 is an important nutrient that is essential for red blood cell formation, DNA synthesis, and many other vital processes. Supplements may help boost mood and reduce symptoms of depression in those who are not deficient in this vitamin.

Since B12 is a water-soluble vitamin, it’s generally considered safe, even at high doses.

No Tolerable Upper Intake Level (UL) has been established for B12, due to its low level of toxicity. UL refers to the maximum daily dose of a vitamin unlikely to cause adverse side effects in the general population.

This threshold has not been set for B12 because your body excretes whatever it doesn’t use through your urine.

However, supplementing with excessively high levels of B12 has been linked to some negative side effects.

Several studies have shown that megadoses of the vitamin can lead to outbreaks of acne and rosacea, a skin condition that causes redness and pus-filled bumps on the face.

Yet, it should be noted that most of these studies focused on high dose injections rather than oral supplements (4, 5, 6).

There is also some evidence suggesting that high doses of B12 may lead to negative health outcomes in those with diabetes or kidney disease.

One 2010 study found that people with diabetic nephropathy (loss of kidney function due to diabetes) experienced a more rapid decline in kidney function when supplemented with high dose B vitamins, including 1 mg per day of B12 (7).

What’s more, the participants receiving the high dose B vitamins had a greater risk of heart attack, stroke, and death, compared to those receiving a placebo. However, more recent studies are needed to support this claim (7, 8).

Another study in pregnant women showed that extremely high B12 levels due to vitamin supplements increased the risk of autism spectrum disorder in their unborn child (9).

Though there is evidence that supplementing with B12 may cause negative health outcomes, studies have demonstrated that daily oral supplements of up to 2 mg (2,000 mcg) are safe and effective in treating B12 deficiency (10).

For reference, the recommended daily intake (RDI) of vitamin B12 is 2.4 mcg for both men and women, though pregnant and breastfeeding women have a higher need (11).

Summary

Although there is some evidence that very high doses of B12 may cause adverse health effects in certain populations, megadoses of this vitamin are commonly used to safely and effectively treat B12 deficiency.

For healthy individuals who are not at risk for B12 deficiency, eating a well-rounded, nutrient-rich diet should provide all the B12 their body needs.

Food sources of this vitamin include eggs, red meat, poultry, seafood, milk, yogurt, fortified cereals, nutritional yeast, and fortified non-dairy milk.

However, individuals taking medications that affect B12 absorption, pregnant or breastfeeding women, vegans, and anyone with a condition that negatively impacts the absorption of or increases the need for B12 should consider talking with their doctor about taking a supplement.

Additionally, evidence from population studies suggests that B12 deficiency in older adults is common, which is why it’s recommended that adults over 50 years old consider taking supplements (12).

While megadoses of up to 2,000 mcg are considered safe in treating B12 deficiency, it’s always best to avoid excessive amounts of any vitamin, especially when it’s not needed.

Though daily high doses of B12 are unlikely to cause harm in most people, extremely high doses should be avoided unless a healthcare professional prescribes it.

If you think you may be deficient in B12, speak with your doctor, who can recommend an appropriate treatment based on your level of deficiency.

While no UL has been set for B12, your body’s ability to absorb the vitamin depends on how much it actually needs.

For example, it’s estimated that only 10 mcg of a 500-mcg B12 supplement is actually absorbed in people without a deficiency (1).

For this reason, taking high doses of B12 does not benefit people without an increased need.

Summary

Although supplemental B12 is required for people with an increased need for this vitamin, it’s unnecessary for those without a deficiency to take high doses.

B12 is an important nutrient that is popularly used as a nutritional supplement, even by those without a B12 deficiency.

Though doses of up to 2,000 mcg of vitamin B12 are considered safe, it’s best to speak with a doctor to find out whether taking a supplement is necessary.

Most people can fulfill their B12 needs through a nutrient-rich diet. However, some people, including older adults and those with certain dietary restrictions, should consider talking with their doctor about supplementation.

Vitamin B12 Deficiency and Weight Gain — What to Know

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Vitamin B12, also known as cobalamin, is a water-soluble vitamin that’s involved in various essential bodily processes.

For instance, your body uses it to make DNA and create new red blood cells, as well as produce energy. It may even affect your mood and memory and is instrumental in helping your brain and nervous system function properly (1, 2, 3).

Therefore, a deficiency in this nutrient can have debilitating health effects.

What’s more, some people have recently suggested that unwanted weight gain be added to the list of possible side effects.

This article reviews the latest scientific evidence to determine whether a vitamin B12 deficiency may result in weight gain.

To absorb vitamin B12 effectively, your body requires an intact stomach and gut, a well-functioning pancreas, and sufficiently high levels of intrinsic factor, a protein that binds to vitamin B12 in the stomach (1).

Adult women require 2.4 mcg of vitamin B12 per day. This requirement increases to 2.8 mcg per day during pregnancy and breastfeeding. Adult men can meet their needs by consuming 2.6 mcg of vitamin B12 per day (1).

Extra vitamin B12 can be stored in the liver, and only small amounts are lost through your urine, sweat, or stools each day. Because of this and the small daily requirements, it can take a year or longer of insufficient vitamin B12 intake to develop an overt deficiency (1).

However, once present, it can have debilitating consequences.

Symptoms of vitamin B12 deficiency include (1):

• chronic fatigue
• shortness of breath
• heart palpitations
• tingling or numbness in the extremities
• poor balance
• loss of concentration
• poor memory
• disorientation
• mood changes
• incontinence
• insomnia

People most at risk of developing a deficiency include older adults, as well as those who smoke, abuse alcohol, or follow a vegetarian or vegan diet.

Gut surgery, pancreatic insufficiency, small intestinal bacterial overgrowth (SIBO), parasite infections, and certain autoimmune disorders are considered additional risk factors.

Moreover, certain medications, including metformin, proton pump inhibitors, and antacids may also reduce your body’s ability to absorb vitamin B12 from your diet (1, 4).

summary

Vitamin B12 deficiency can manifest itself through a variety of symptoms. People most at risk of deficiency include older adults, vegans, and those with specific medical conditions or taking certain medications.

Despite the numerous processes in which vitamin B12 is involved, there’s little evidence to suggest that it has any influence on weight gain or loss.

Most of the evidence giving rise to this claim comes from a few observational studies.

For instance, one study notes that people with excess weight or obesity appear to have lower vitamin B12 levels than people who have a body mass index (BMI) in the “normal” range (5).

Additional research has observed that people who voluntarily took vitamin B12 supplements gained between 2.5–17 fewer pounds (1.2–7.7 kg) over 10 years than those who did not supplement with this vitamin (6).

Still, such observational studies cannot confirm whether low vitamin B12 levels are what caused the weight gain, nor whether they’re what protected against low levels.

On the other hand, a vitamin B12 deficiency appears to cause a loss of appetite in some people, leading to weight loss rather than weight gain (7, 8).

That said, the current evidence is too weak to suggest that a vitamin B12 deficiency has any strong or specific impact on weight — be it weight gain or loss.

summary

There’s little evidence to support the notion that vitamin B12 deficiency causes weight gain. More studies are needed before such strong statements can be made.

Vitamin B12 is found exclusively in animal foods or foods fortified with this vitamin, such as:

• Meat and chicken: especially organ meat and red meat like beef
• Fish and seafood: especially clams, sardines, tuna, trout, and salmon
• Dairy: including milk, cheese, and yogurt
• Eggs: especially egg yolk
• Fortified foods: breakfast cereal, nutritional yeast, as well as some mock meats or plant milks

Supplements, which are widely available in stores and online, are another way to meet your daily requirements.

They’re especially handy for people with low levels of intrinsic factor, a protein that helps your body absorb vitamin B12 more easily (9).

Additionally, they can help those who have difficulty consuming sufficient amounts of the foods above meet their daily vitamin B12 needs. This may include vegetarians or vegans who don’t plan their diet carefully (10, 11).

summary

Vitamin B12 can be found in animal products, as well as foods fortified with it. Supplements are a practical way for some people to ensure they meet their daily vitamin B12 requirements.

Vitamin B12 is a water-soluble vitamin that your body uses for a variety of processes, including producing energy and maintaining a healthy brain and nervous system.

Sources of vitamin B12 include animal foods, vitamin-B12-fortified foods, and supplements.

People with vitamin B12 deficiency are likely to experience a wide range of symptoms, though weight gain is unlikely one of them.

If you’re experiencing unexplained weight gain, consider discussing it with your healthcare provider or a registered dietitian to determine the root cause.

Side effects of vitamin B12 supplements

Overview

Since 1970, several cases of rosacea and acne have been described in the scientific literature as a result of vitamin B12 treatment. Few people get this reaction, but if you notice a rash after taking large doses of vitamin B12, stop supplementing and follow the recommendations for getting the vitamin from fortified foods or significantly lower doses of vitamin B12.

Additive safety

It is believed that large doses of vitamin B12 are not harmful. The general consensus can be summarized by a quote from the Linus Pauling Institute, Oregon: “No toxic or side effects have been found with high intakes of vitamin B12 from food or supplements in healthy individuals. For the treatment of pernicious anemia, doses greater than 1 mg (1000 mcg) of the vitamin orally daily have been used or 1 mg injection intramuscularly once a month without significant side effects.

Thematic presentations

We have received several emails from people reporting their body’s response to high doses of vitamin B12 (usually 1,000 mcg). In addition, numerous thematic reports can be found in the literature, one of the latest for 2001:

A 17-year-old girl from Germany developed a flare-up of rosacea after two weeks of taking 80 mg of vitamin B6 and 20 µg of vitamin B12 daily (Jansen, 2001). These dosages are not high.

She was diagnosed with rosacea fulminans caused by excess vitamin B. The girl was prescribed to stop taking vitamin B supplements and was treated with methylprednisolone, isotretinoin, and clobetasol propionate. The treatment was successful and prevented skin changes in 4 months without leaving any residual scarring.

The authors state: “Vitamins B2 (riboflavin), B6 ​​(pyridoxine), and B12 (cyanocobalamin) are known to aggravate acne or lead to breakouts.”

A 1991 issue paper from North Carolina stated: “This case illustrates an outbreak of rosacea that was temporarily triggered by daily high-dose vitamin B supplementation. Such an outbreak does not respond to conventional rosacea treatment regimens, but improves rapidly when vitamin supplements are discontinued.” (Sherertz, 1991)

An extract from a German article states that 14 patients developed acne from treatment with vitamin B6 and/or vitamin B12 (Braun-Falco, 1976). Dosages were not specified.

Safety of cyanocobalamin

The safety of cyanocobalamin is of concern due to cyanide being a component of cyanocobalamin. The cyanide molecule is removed from cyanocobalamin when used by the cells of the body. Cyanide is also found in many fruits and vegetables, and people regularly ingest small amounts of cyanide. And, as with most fruits and vegetables, the amount of cyanide in cyanocobalamin is considered physiologically negligible.

According to a statement from the European Food Safety Authority: “Data from the Norwegian Dietary Study show that at average and high (97.5 percentile) daily consumption [cyanide] among consumers, the amount consumed was respectively 95 and 372 µg/person or 1. 4 and 5.4 µg/kg body weight per day (7)”. The amount of cyanide in cyanocobalamin 1,000 mcg supplement is 20 mcg.

Table 1 provides some additional information on the amounts of cyanide in cyanocobalamin.

Table 1. Cyanide content of cyanocobalamin
Molecular weight of vitamin B12	1355 g/mol
Molecular weight of cyanide	27 g/mol
Percent cyanide in vitamin B12	2.0%
Amount of cyanide in 1000 micrograms of cyanocobalamin	20 micrograms
Minimum risk level for oral cyanide a (4)	0.05 mg/kg body weight per day
Minimum risk level for 140 lb human oral cyanide (approximately 63.5 kg)	3175 mcg/day
Lethal dose of cyanide (5)	0.5 to 3.0 mg/kg body weight
140 lb human lower lethal dose limit for cyanide	31750 micrograms
Percent lethal dose for a 140 lb human in 1000 micrograms of cyanocobalamin	0. 06%
a The minimum risk level does not include cancer risk (6).

Cyanocobalamin and kidney disease

People with kidney disease should not take large doses of cyanocobalamin, as in most cases they cannot absorb cyanide effectively.

References

1. Jansen T, Romiti R, Kreuter A, Altmeyer P. Rosacea fulminans triggered by high-dose vitamins B6 and B12. J Eur Acad Dermatol Venereol. 2001 Sep;15(5):484-5.

2. Sherertz EF. Acneiform eruption due to “megadose” vitamins B6 and B12. cutis. 1991 Aug;48(2):119-20.

3. Braun-Falco O, Lincke H. [The problem of vitamin B6/B12 acne. A contribution on acne medicamentosa (author’s transl)]. MMW Munch Med Wochenschr. 1976 Feb. 6;118(6):155-60. | Abstract (article in German)

4. ToxGuide for Cyanide. Agency for Toxic Substances and Disease Registry. Centers for Disease Control. July 2006. Accessed 2/7/2012.

5. Natural Toxins in Fresh Fruit and Vegetables. Canadian Food Inspection Agency. Accessed 2/8/2012.

6. Minimal Risk Levels. Toxic Substances Portal. Agency for Toxic Substances and Disease Registry. Centers for Disease Control. Accessed 2/8/2012.

7. Opinion of the Scientific Panel on Food Additives, Flavourings, Processing Aids and Materials in Contact with Food (AFC) on hydrocyanic acid in flavorings and other food ingredients with flavoring properties. The EFSA Journal (2004) 105.

Overdose of vitamins A, D, E, C and others

Vitamins are vital substances, deficiency of which causes disease. However, thoughtlessly exceeding dosages can cause an overdose. This article discusses the consequences of taking high doses of various vitamins and, where known, indicates the maximum allowable daily intake.

Vitamin A

Vitamin A overdose is quite rare due to a number of reasons:

• relatively inefficient metabolism of provitamin A in the intestine,
• unidirectional oxidation of retinoic acid, which is rapidly catabolized and excreted from the body,
• high ability of CRBP to bind retinol,
• vitamin A storage in the liver.

Therefore, the doses required to develop the toxic effects of vitamin A are quite large (the first signs of hypervitaminosis occur when plasma retinol levels are above 3 µmol/l).

The main symptoms of vitamin A overdose are: drowsiness, irritability, headache, abdominal pain, nausea, vomiting, convulsions. In chronic poisoning, hepatosplenomegaly, dry skin, hyperpigmentation, alopecia of eyelashes and eyebrows, brittle nails, pain in bones and joints, and sometimes excessive growth of bone tissue develop. In addition, the teratogenicity of one of the vitamin A metabolites has been proven, therefore, after an overdose, it is recommended to use contraception during one menstrual cycle.

Beta-carotene, found in vegetables such as carrots, is slowly converted into vitamin A in the body. Consuming large amounts of these vegetables can lead to carotenoses (yellowing of the skin, especially on the palms and soles), but does not appear to causes any toxic effects.

The maximum allowed intake of vitamin A for adults is 3000 mcg/day [1, pp. 153-156].

Relationship between vitamin A intake and clinical symptoms (original figure).

Vitamin D

Hypervitaminosis D is associated primarily with the consumption of high doses of vitamin-containing dietary supplements, since there are no reported cases of hypervitaminosis associated with excessive exposure to sunlight.

In young children, hypervitaminosis D develops when taking 40,000 IU/day for 1-4 months, in adults – more than 100,000 IU/day. It is characterized by the development of hypercalcemia as a result of increased intestinal absorption and resorption of calcium in the bones and a concomitant decrease in serum parathyroid hormone levels. In case of vitamin D poisoning, anorexia, nausea, vomiting, diarrhea, polyuria, headache, weakness, less often – arrhythmias, convulsions occur. In addition, calcification develops – calcium deposition in soft tissues (heart and blood vessels, kidneys, organs of the respiratory system, and others), and urolithiasis. The risk is especially increased when taking vitamin D and calcium at the same time. An overdose of vitamin D during pregnancy causes an increase in the frequency of spontaneous abortions, as well as the development of fetal hypercalcemia, which is manifested by intrauterine growth retardation (hypotrophy, dysplasia), aortic valve stenosis, fibroelastosis, and dysplasia of the tooth germs [1, pp. 202-204].

Recommended upper intake levels for vitamin D

Vitamin E

Vitamin E is considered one of the least toxic vitamins. Daily doses up to 400 IU are considered harmless, and high doses (up to 3200 IU) when taken orally do not cause persistent side effects. However, there are anecdotal reports of adverse effects in people consuming up to 1,000 IU of vitamin E per day. These side effects include headache, fatigue, nausea, double vision, muscle weakness, mild creatinuria, and dyspepsia. In addition, when taking high doses of vitamin E, there is a risk of impaired absorption and metabolism of other fat-soluble vitamins (A, D and K), which leads to changes in bone mineralization, the development of coagulopathy (important for patients receiving anticoagulants), a decrease in the concentration of vitamin A in liver. Premature infants given mega-doses of vitamin E may develop necrotizing enterocolitis and sepsis.

It is practically impossible to achieve a high dietary intake of vitamin E, so an overdose is mainly associated with a high intake of biological supplements [1, p. 239, 2].

Tolerable upper intake levels for vitamin E

Vitamin K

Overdose of vitamin K (phylloquinone, menaquinone) is rare. Menaquinone is considered to be more toxic than phylloquinone. So, for example, when the level is exceeded by three orders of magnitude, it causes oxidative stress, hemolytic anemia, hyperbilirubinemia and severe jaundice. Symptoms of the hemolytic syndrome are very characteristic of neonatal hypervitaminosis K. In turn, phylloquinone is associated with a risk of chronic kidney disease. Some patients who received phylloquinone intramuscularly or subcutaneously developed persistent localized eczematous plaques at the injection site. Upper tolerated intake levels for vitamin K have not been established. The daily dose of vitamin K for an adult man is 120 mcg, and for a woman – 90 µg [1, pp. 262-263].

Vitamin C

No significant side effects of ascorbic acid (vitamin C) have been identified. High doses of the vitamin both orally and intravenously do not cause the development of significant side effects. However, there are reports of gastrointestinal disturbances and diarrhea with megadoses of vitamin C. Hypervitaminosis C is also associated with the risk of developing oxaluria (oxalate in the urine) and the potential for urolithiasis, since oxalate is the main metabolite of ascorbic acid. In addition, vitamin C supplementation may enhance enteral absorption of iron and subsequent accumulation in tissues, so supplements containing this vitamin are not recommended for patients with hemochromatosis. On the other hand, despite the possibility of these side effects, the risk of their development, apparently, is small.

Other hypothesized effects caused by excess vitamin C intake, such as: uricosuria (increase in uric acid in the urine), vitamin B12 deficiency, “rebound scurvy” (increased catabolism of vitamin C and symptoms of deficiency with reduced dosage) have not been confirmed in studies [ 1, pp. 292-293; 3].

Tolerable upper intake levels for vitamin C

Vitamin B1

Vitamin B1 (thiamine) is generally well tolerated at therapeutic doses (up to 100 mg/day), but allergic reactions are not uncommon, including inhaled substances (vitamin B1 injectables). very volatile). In case of an overdose, it can inhibit the activity of cholinesterase (curare-like signs) and histaminase (allergic reactions and anaphylactic shock). Vitamin B1 poisoning is accompanied by tremor, anxiety, shortness of breath, cyanosis, pharyngeal spasm, fever, sweating, and a decrease in blood pressure. have a specific smell. Tolerable upper intake levels for thiamine have not been established. The daily requirement for adults in vitamin B1 is 1.5 mg/day [1, p.113; 4].

Vitamin B2

The toxicity of vitamin B2 (riboflavin) is very low due to poor oral absorption and rapid urinary excretion. Even at doses of 2-10 g/kg of body weight, vitamin B2 does not cause side effects when taken orally. When administered parenterally, riboflavin is slightly more toxic. It was shown that the LD50 (semi-lethal dose) for rats treated with riboflavin i.p., subcutaneously and orally was 0.6 g/kg, 5 g/kg and >10 g/kg, respectively.

Due to the low toxicity, the symptoms of an overdose of riboflavin are practically not described. The most likely symptoms are impaired liver and kidney function, pain in the right side, diarrhea, visual impairment. The daily requirement for the vitamin is 1-3 mg. The upper permissible exposure limits have not been established [1, p. 328].

Vitamin B3

Vitamin B3 (PP, nicotinic acid) has low toxicity. The most common side effect of taking it in high doses is flushing of the skin caused by vasodilatation of the skin vessels. This reaction is transient (30–90 min) and is accompanied by erythema, tingling, itching and fever. It occurs in approximately 70% of patients at the beginning of therapy and most often resembles the development of tolerance. The flushing reaction can be caused by both oral and topical exposure to nicotinic acid, which triggers the release of prostaglandin D2 from platelets and dendritic cells. The reaction can be minimized by using a slow-release nicotinic acid preparation or by using a cyclooxygenase inhibitor (eg, aspirin) before taking the drug. High doses of nicotinic acid have also been reported to cause itching, urticaria, and gastrointestinal disturbances (heartburn, nausea, vomiting, and sometimes diarrhea).

Long-term effects of high doses of nicotinic acid include insulin resistance, hyperuricemia, ulcerogenic effects on the gastric mucosa, liver damage. A few cases of transient elevations of plasma liver enzymes without associated hepatic dysfunction have also been reported. The maximum daily dose of vitamin PP for an adult is 500 mg [1, p. 348].

Vitamin B5

The toxicity of vitamin B5 (pantothenic acid) is negligible. It has been estimated that animals can tolerate doses of pantothenic acid at least 100 times their daily requirement without adverse effects. In humans, high doses of vitamin B5 (10 g/day) have only caused mild gastrointestinal distress and diarrhea. An upper tolerated intake level for pantothenic acid has not been established. The recommended daily intake of pantothenic acid for adults is 5-10 mg (in some sources – up to 15) [1, p. 397].

Vitamin B6

The toxicity of vitamin B6 (pyridoxine) is relatively low, although high doses (greater than 2 g per day) have been shown to cause sensory neuropathy characterized by gait changes, fine motor impairment, and loss of proprioceptive and vibrational sensitivity (in preservation, as a rule, pain, temperature and tactile). In addition, at doses of 10-25 mg, pyridoxine has been shown to increase the conversion of levodopa to dopamine, which, unlike its predecessor, does not cross the blood-brain barrier. Thus, B6 should not be administered to individuals taking levodopa without concomitant administration of a decarboxylase inhibitor. Upper Tolerable Intakes of Vitamin B6 have not been established [1, p. 369; 5].

Vitamin B7

The toxicity of vitamin B7 (H, biotin) is very low. Adverse reactions were not noted even when taking the vitamin in high doses (up to 200 mg orally or 20 mg intravenously). Animal studies have not shown any significant evidence of biotin toxicity, suggesting that animals, including humans, can tolerate the vitamin at doses at least an order of magnitude greater than their respective dietary requirements. The daily requirement for biotin is 50 mcg/day for adults. The maximum allowable levels of biotin intake have not been established [1, p. 383].

Vitamin B9

Folic acid (vitamin B9) has low toxicity. In general, oral intake of large amounts of folic acid does not cause significant side effects, however, there is a potential association between high doses of folate and epileptic reactions. They have been shown to occur in rats (1,000 times the daily allowance for parenteral administration) as well as in humans with epilepsy (controversial data, but according to some, high doses of folic acid (1–10 mg) were associated with an increase in the frequency and seizure severity). Taking large amounts of folic acid by pregnant women increases the risk of having babies that are small for gestational age. In addition, folate overdose can also potentially exacerbate the effects of vitamin B12 deficiency [1, p. 427; 6, 7].

Recommended Tolerable Intakes for Folic Acid

mcg/day

Vitamin B12

Vitamin B12 (cyanocobalamin) has no appreciable toxicity. The results of studies in mice show that it is harmless when administered parenterally in mega-doses. Excess of vitamin B12 by several hundred times when taken orally does not cause significant side effects. At the same time, a high level of vitamin B12 in the blood is most often associated not with hypervitaminosis, but with the presence of serious diseases. Thus, a relationship was shown between an increased concentration of vitamin B12 in the blood serum and solid neoplasms (hepatocellular carcinoma and secondary liver tumors, breast cancer, colon cancer, stomach cancer and pancreatic tumors), hemoblastoses (chronic myelomonocytic leukemia, primary hypereosinophilic syndrome, acute myeloid leukemia, etc. ), liver diseases (acute hepatitis, cirrhosis, alcoholic liver damage, etc.), kidney diseases. The norm of B12 in serum varies on average from 190 to 663 pg/ml. The daily requirement for vitamin B12 in adults is 3.0–3.4 μg [1, p. 450; 8].

Sources:

1. The Vitamins: Fundamental Aspects in Nutrition and Health 5th Edition / Gerald F. Combs Jr. (Author), James P. McClung // ‎ Academic Press; 5th edition, 2017. 628 pages.
2. Abner E.L., et al. Vitamin E and all-cause mortality: a meta-analysis. Curr Aging Sci. 2011, Vol.4, No.2, pp.158-170.
3. Mühlhofer A., ​​et al. High-dose intravenous vitamin C is not associated with an increase of pro-oxidative biomarkers. Eur J Clinic Nutr. 2004, Vol.58, No.8, pp.1151-1158.
4. Gromova O.A. Vitamin B1. Pediatric practice, school on vitamins and microelements. March 2005.
5. Mars H. Levodopa, carbidopa, and pyridoxine in Parkinson disease. Metabolic interactions. Arch Neurol. 1974 Vol. 30, No. 6, pp. 444-447
6. Moore J/L.