Can you take too much vitamin B. What are the symptoms of vitamin B toxicity. How much vitamin B is considered safe to consume daily. Are there risks associated with excessive vitamin B intake. Which B vitamins are most likely to cause toxicity.

The Importance of B Vitamins and Potential Risks of Overconsumption

Vitamins are essential for maintaining good health, but excessive intake can lead to adverse effects. B vitamins, in particular, are crucial for various metabolic functions in the body. However, as these vitamins are commonly found in supplements and fortified foods, there is a risk of overconsumption.

There are eight B vitamins, each playing a unique role in the body:

• Thiamine (B1)
• Riboflavin (B2)
• Niacin (B3)
• Pantothenic acid (B5)
• Pyridoxine (B6)
• Biotin (B7)
• Folic acid (B9)
• Cobalamin (B12)

These vitamins function as enzymatic cofactors or precursors, enabling many basic metabolic processes in the body. While vitamin toxicity is relatively rare, it’s essential to understand the potential risks associated with excessive intake.

Vitamin B1 (Thiamine): Low Risk of Toxicity

Thiamine is generally considered non-toxic, even at higher doses. The recommended daily allowance (RDA) for vitamin B1 is:

• Adults: 1.5 mg per day
• Children (ages 1-4): 0.7 mg per day

Is there a risk of thiamine toxicity? Thiamine is water-soluble, and excess amounts are typically excreted in urine. As a result, toxicity from vitamin B1 is extremely rare, even with high supplementation.

Vitamin B2 (Riboflavin): Generally Safe at Higher Doses

Similar to thiamine, riboflavin is considered non-toxic. The RDA for vitamin B2 is:

• Adults: 1.7 mg per day
• Children (ages 1-4): 0.8 mg per day

Can riboflavin cause adverse effects at high doses? While extremely high doses of riboflavin may cause minor side effects like increased urine production or diarrhea, serious toxicity is not a concern for most people.

Vitamin B3 (Niacin): Potential for Side Effects at Higher Doses

Niacin has a higher potential for side effects compared to other B vitamins. The RDA for vitamin B3 is:

• Adults: 20 mg per day
• Children (ages 1-4): 9 mg per day

While there is no established toxic dose in humans, doses higher than 50 mg per day can cause side effects such as skin flushing. Therapeutic doses of 1500 to 1600 mg per day may be prescribed for certain conditions but carry a risk of liver toxicity, especially in individuals with pre-existing liver disease.

In 2015, there were 1,374 reported cases of niacin toxicity. This highlights the importance of being cautious with niacin supplementation and following recommended dosages.

Vitamin B5 (Pantothenic Acid): Low Risk of Toxicity

Pantothenic acid is generally considered safe, even at higher doses. The recommended adequate intake for vitamin B5 is:

• Adults: 5 mg per day

Is there a tolerable upper intake level for pantothenic acid? No tolerable upper intake level has been established for vitamin B5. However, very high doses (10 to 20 grams per day) have been associated with diarrhea in some cases.

Vitamin B6 (Pyridoxine): Potential for Neurotoxicity at High Doses

Vitamin B6 requires more caution compared to some other B vitamins. The RDA for pyridoxine is:

• Adults (19-50 years): 1.3 mg per day

While an acute toxic dose has not been established, long-term consumption of 300 to 500 mg per day may cause neurotoxicity. In 2015, 189 cases of vitamin B6 toxicity were reported, emphasizing the need for careful supplementation.

What are the symptoms of vitamin B6 toxicity? Symptoms may include nerve damage, skin lesions, photosensitivity, and nausea. If you experience any of these symptoms while taking B6 supplements, consult a healthcare professional immediately.

Vitamin B7 (Biotin): Low Risk of Toxicity

Biotin plays a crucial role in gene regulation and is considered safe at higher doses. The recommended intake for vitamin B7 is:

• Adults: 30 mcg per day

Is there a risk of biotin toxicity? Biotin is not considered toxic, and no tolerable upper intake level has been established. Even at high doses, adverse effects are rare.

Vitamin B9 (Folic Acid): Potential Masking of B12 Deficiency

Folic acid is essential for various bodily functions, but excessive intake can pose certain risks. The RDA for vitamin B9 varies based on age and life stage:

• Adults (14+ years): 400 mcg per day
• Pregnant women: 600 mcg per day
• Lactating women: 500 mcg per day

What is the safe upper limit for folic acid intake? The safe upper limit for adults is 1000 mcg per day from fortified foods and supplements. Exceeding this amount may mask the signs of vitamin B12 deficiency, particularly in older adults.

Why is masking B12 deficiency a concern? B12 deficiency can lead to neurological problems and anemia. By masking these symptoms, high folic acid intake may delay diagnosis and treatment of B12 deficiency, potentially leading to more severe health issues.

Vitamin B12 (Cobalamin): Low Risk of Toxicity

Vitamin B12 is essential for nerve function and DNA synthesis. The RDA for cobalamin is:

• Adults (14+ years): 2.4 mcg per day

Is there a risk of vitamin B12 toxicity? No tolerable upper intake level has been established for vitamin B12. It is generally considered safe, even at high doses, as excess B12 is typically excreted in urine.

General Symptoms of Vitamin B Toxicity

While specific symptoms may vary depending on the particular B vitamin involved, general signs of vitamin toxicity can include:

• Nausea
• Gastrointestinal issues (constipation or diarrhea)
• Hair loss
• Skin rashes
• Nerve damage

It’s important to note that vitamin overdose and toxicity rarely lead to death or serious illness. In 2012, the American Association of Poison Control Centers reported 59,028 exposures to vitamin toxicity, with only one resulting in death.

Preventing Vitamin B Toxicity

To avoid the risk of vitamin B toxicity, consider the following precautions:

1. Follow recommended daily allowances
2. Be cautious when combining supplements with fortified foods
3. Consult a healthcare professional before starting any new supplement regimen
4. Pay attention to the dosages listed on supplement labels
5. Be aware of potential interactions with medications

Are there specific populations at higher risk for vitamin B toxicity? Individuals with pre-existing health conditions, particularly liver or kidney disease, may be more susceptible to vitamin B toxicity. Additionally, older adults should be cautious with high doses of folic acid due to the potential masking of B12 deficiency.

The Role of Fortified Foods in Vitamin B Intake

Fortified foods play a significant role in vitamin B intake for many people. Common fortified foods include:

• Breakfast cereals
• Bread and pasta products
• Plant-based milk alternatives
• Energy bars and drinks

While fortification helps prevent nutrient deficiencies, it’s essential to be aware of your total vitamin B intake from both food and supplements to avoid excessive consumption.

How can you balance vitamin B intake from fortified foods and supplements? Keep track of the fortified foods in your diet and consider their nutrient content when deciding whether to take additional supplements. If you consume a variety of fortified foods regularly, you may not need high-dose B vitamin supplements.

Natural Sources of B Vitamins

While supplements and fortified foods are common sources of B vitamins, many natural foods are rich in these essential nutrients. Some excellent sources include:

• Whole grains (for thiamine, niacin, and folate)
• Lean meats (for B12, niacin, and B6)
• Eggs (for B12 and biotin)
• Legumes (for folate and B6)
• Nuts and seeds (for thiamine, niacin, and B6)
• Leafy green vegetables (for folate and B2)
• Fish (for B12 and niacin)
• Dairy products (for B12 and B2)

Incorporating a variety of these foods into your diet can help ensure adequate B vitamin intake without the risk of overconsumption associated with high-dose supplements.

Special Considerations for Vitamin B Supplementation

While vitamin B toxicity is rare, certain situations may warrant careful supplementation:

Pregnancy and Lactation

Pregnant and breastfeeding women often require higher amounts of certain B vitamins, particularly folate. However, it’s crucial to follow healthcare provider recommendations to avoid excessive intake.

Vegetarian and Vegan Diets

Individuals following plant-based diets may need B12 supplementation, as this vitamin is primarily found in animal products. However, other B vitamins are readily available in plant-based foods.

Older Adults

As we age, the body’s ability to absorb certain B vitamins, particularly B12, may decrease. Older adults should consult with their healthcare provider about appropriate supplementation.

Certain Medical Conditions

Some health conditions, such as Crohn’s disease or celiac disease, may impair B vitamin absorption, necessitating supplementation. However, this should always be done under medical supervision.

How can you determine if you need vitamin B supplementation? A blood test can help identify any B vitamin deficiencies. Based on the results, your healthcare provider can recommend appropriate supplementation if necessary.

The Impact of Vitamin B on Overall Health

B vitamins play crucial roles in maintaining overall health and well-being. Some key functions include:

• Energy production
• Red blood cell formation
• Nervous system function
• DNA synthesis and repair
• Hormone and cholesterol production
• Immune system support

While adequate intake is essential, it’s important to remember that more is not always better. Excessive intake of certain B vitamins can lead to adverse effects and may not provide additional health benefits.

How do B vitamins contribute to energy metabolism? B vitamins act as coenzymes in various metabolic processes, helping convert the food we eat into usable energy for our cells. This is why B vitamins are often associated with increased energy levels, although they don’t provide energy directly.

Interactions Between B Vitamins and Medications

Some medications can interact with B vitamins, either affecting their absorption or altering their effects in the body. Common interactions include:

• Metformin (diabetes medication) may reduce B12 absorption
• Proton pump inhibitors (for acid reflux) can decrease B12 absorption
• Certain antibiotics may interfere with B vitamin absorption
• Some seizure medications can affect folate levels

It’s crucial to inform your healthcare provider about all supplements you’re taking, including B vitamins, to avoid potential interactions with prescribed medications.

How can you manage potential interactions between B vitamins and medications? Always consult with your healthcare provider or pharmacist before starting any new supplement regimen, especially if you’re taking prescription medications. They can advise on potential interactions and adjust dosages if necessary.

The Future of Vitamin B Research

Ongoing research continues to explore the potential benefits and risks associated with B vitamins. Some areas of current interest include:

• The role of B vitamins in cognitive function and neurodegenerative diseases
• The potential of high-dose B vitamins in cancer prevention
• The impact of genetic variations on B vitamin metabolism and requirements
• The development of more bioavailable forms of B vitamins for supplementation

As research progresses, our understanding of optimal B vitamin intake and potential risks of overconsumption may evolve. It’s important to stay informed about the latest findings and recommendations from reputable health organizations.

How might future research impact vitamin B supplementation guidelines? Advances in personalized nutrition and genetic testing may lead to more tailored recommendations for B vitamin intake based on individual needs and genetic profiles. This could help optimize the benefits of B vitamins while minimizing the risk of toxicity.

Conclusion: Balancing B Vitamin Intake for Optimal Health

While B vitamins are essential for numerous bodily functions, it’s crucial to maintain a balanced approach to intake. Most people can obtain adequate B vitamins through a varied diet rich in whole foods. Supplementation may be necessary for certain populations or under specific circumstances, but should always be done under the guidance of a healthcare professional.

Understanding the potential risks of excessive B vitamin intake, as well as the symptoms of toxicity, can help individuals make informed decisions about their nutrition and supplement use. By staying aware of both dietary sources and supplemental intake, it’s possible to reap the benefits of B vitamins while minimizing the risk of adverse effects.

Remember, when it comes to vitamins and nutrition, more is not always better. Strive for balance, variety, and moderation in your diet, and consult with healthcare professionals when considering supplement use. By doing so, you can support your body’s needs without risking the potential complications of vitamin B toxicity.

Can You Take Too Much Vitamin B?

Vitamins are required for life. A minimum daily dose of each vitamin is necessary to maintain good health. Significantly exceeding this dose, however, can cause illness. In general, the symptoms of vitamin toxicity include nausea, gastrointestinal problems like constipation and diarrhea, hair loss, rashes, and nerve damage.

It is unusual to overdose on vitamins through megadose supplements, but people sometimes receive an unsafe dose of some vitamins by combining fortified foods with supplements.

Foods containing vitamin B 6: hazelnuts, potatoes, oatmeal, raisin, buckwheat, walnuts – Image Copyright: Elena Hramova / Shutterstock

Vitamin overdose and toxicity rarely leads to death or serious illness. In 2012, the American Association of Poison Control Centers reported 59,028 exposures and only one death.

As B vitamins are often given as supplements and found in fortified foods, there is some risk of taking too much B vitamin. There are eight B vitamins; thiamine, ribovlavin, niacin, pantothenic acid, pyridoxine, biotin, folic acid, and cobalamine. Each functions as an enzymatic cofactor or is a precursor to an enzymatic cofactor enabling many of the basic functions of metabolism in the body.

Vitamin B1

The recommended daily allowance (RDA) of vitamin B1 (thiamin) is 1.5 mg per day for an adult, and 0.7 mg for children age 1 to 4. Thiamine is generally nontoxic.

Vitamin B2

The RDA for vitamin B2 (riboflavin) is 1.7 mg for adults and 0.8 mg for children age 1 to 4. Vitamin B2 is also generally nontoxic.

Vitamin B3

The RDA for vitamin B3 (niacin) is 20 mg for adults, and 9 mg for children between 1 and 4. There is no toxic dose established in humans. However, at doses higher than 50 mg per day, some side effects such as skin flushing can occur. Therapeutic doses of 1500 to 1600 mg per day can be given, but with a risk of liver toxicity, especially in the presence of pre-existing liver disease. There were 1374 exposures to niacin toxicity reported in 2015.

Vitamin B5

The recommended adequate intake of vitamin B5 (pantothenic acid) is 5 mg per day for adults. It is not known to be toxic in humans and there is no tolerable upper intake level established. Diarrhea has been documented at intakes of 10 to 20 g per day.

Vitamin B6

The RDA for vitamin B6 (pyridoxine) is 1.3 mg for adults between 19 and 50 years.  . An acute toxic dose has not been established but it is known that vitamin B6 may cause neurotoxicity at a dose of 300 to 500 mg per day over time. In 2015, 189 toxic exposures were reported for Vitamin B6.

Vitamin B7

Vitamin B7 (biotin) is a cofactor for key enzymes in the process of gene regulation. The recommended intake of biotin is 30 mcg per day in adults. Biotin is not considered to be toxic, and no tolerable upper intake level has been established.

Vitamin B9

The RDA for vitamin B9, folic acid, is 400  mcg per day for people over 14, 600 mcg for pregnant women, and 500 mcg for lactating women. Requirements for children are dependent on age. The safe upper limit of folic acid for adults is 1000 mcg from fortified foods and supplements. Taking more than that could conceal the signs of a vitamin B12 deficiency in older people.

Vitamin B12

The RDA for vitamin B12 (cobalamine) is 2.4 mcg for people over age 14. The RDA for children is dependent on age. No tolerable upper intake level for vitamin B12 is established.

Sources

1. Emedicine, Vitamin Toxicity, http://emedicine.medscape.com/article/819426-overview
2. Getting Too Much of Vitamins and Minerals, http://www.webmd.com/diet/guide/effects-of-taking-too-many-vitamins#1
3. Linus Pauling Institute, Micronutrient Information Center, Pantothenic Acid, http://lpi.oregonstate.edu/mic/vitamins/pantothenic-acid
4. Linus Pauling Institute, Micronutrient Information Center, Biotin, http://lpi.oregonstate.edu/mic/vitamins/biotin
5. MedlinePlus, Niacin, https://medlineplus. gov/ency/article/002409.htm
6. National Institutes of Health, Riboflavin: Fact Sheet for Health Professionals, https://ods.od.nih.gov/factsheets/Riboflavin-HealthProfessional/

Further Reading

Thiamin | Linus Pauling Institute

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71.  Naito E, Ito M, Yokota I, Saijo T, Ogawa Y, Kuroda Y. Diagnosis and molecular analysis of three male patients with thiamine-responsive pyruvate dehydrogenase complex deficiency. J Neurological Sci. 2002;201(1-2):33-37.  (PubMed)

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73.  Lee EH, Ahn MS, Hwang JS, Ryu KH, Kim SJ, Kim SH. A Korean female patient with thiamine-responsive pyruvate dehydrogenase complex deficiency due to a novel point mutation (Y161C)in the PDHA1 gene. J Korean Med Sci. 2006;21(5):800-804.  (PubMed)

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75.  Shaw-Smith C, Flanagan SE, Patch AM, et al. Recessive SLC19A2 mutations are a cause of neonatal diabetes mellitus in thiamine-responsive megaloblastic anaemia. Pediatr Diabetes. 2012;13(4):314-321.  (PubMed)

76.  Akin L, Kurtoglu S, Kendirci M, Akin MA, Karakukcu M. Does early treatment prevent deafness in thiamine-responsive megaloblastic anaemia syndrome? J Clin Res Pediatr Endocrinol. 2011;3(1):36-39.  (PubMed)

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Vitamin B1 – Deficiency / Overdose

Deficiency

Vitamin B1 deficiency occurs in people with poor eating habits, the poor people which is often lacking in diversity of food, but also in patients suffering from organic diseases, especially alcoholism. It is therefore B1-deficiency (avitaminosis) disease most common in developed countries. Alcohol reacts with all nutrients, but especially with vitamin B1.

In addition, some raw fish containing unstable enzyme – thiaminase, (which is normally breaked down during thermal processing of fish), which breaks down vitamin B1. This enzyme was first metioned when appeared “Částek paralysis” in foxes fed with food containing not enough amount of vitamin B1. The disease is characterized by anorexia (loss of appetite), fatigue, progressive ataxia (inability to perform coordinated movements), certain types of paraplegia (paralysis of certain parts of the body), and hypertension.

In patients with thiamine deficiency, reactions that depend on thiamine pyrophosphate were prevented or significantly reduced, leading to an accumulation of its substrate, such as pyruvate, pentose and some derivatives of amino acids.

Beri-beri

Beriberi is a disease that occurs in the absence of vitamin B1. When deficiency of vitamin B1 hits the nervous system, producing symptoms of mental confusion and vision disorder dry beriberi occur. It leads to muscle weakness, which can lead to paralysis, especially some of the eye muscles. There is also greater sensitivity in the legs and feet.

Wet beriberi involves a deficiency of vitamin B1 in the heart and circulatory system. In this case, it is disturbed heart rhythm, respiration becomes irregular and short, legs and feet begin to swell, blood pressure decreases, there are also pain in the stomach and kidney disorders. The most extreme manifestation of this type of beriberi is called Shoshin beriberi. This is a Japanese term that refers to a disorder of the heart. This disorder is characterized by reduced activity of the heart, due to buildup of lactic acid in the blood, leading, if not treated appropriately, in death.

Children suffering from beriberi

(Image taken from Hubpages)

The disease often occurs in young people who excessive consume alcohol, especially if accompanied by inadequate nutrition.

Overdose (hypervitaminosis, intoxication)

It is very rare vitamin B1 overdose due to excretion of any excess in urine.

Few symptoms of overdosing are chills, swelling, nervousness, increased heart rate and allergies.

Vitamin B1 (Thiamine) Article

Continuing Education Activity

Vitamin B1 is one of the eight B vitamins, also known as thiamin (thiamine). Because thiamin can only be stored in the body for a short time before it is readily excreted, a regular dietary intake of thiamin is necessary to maintain proper blood levels. The recommended daily intake (RDI) for adults over age eighteen is 1.2 mg/day for men and 1.1 mg/day for women. For children, adequate intake levels are lower. Women of any age who are pregnant or should increase their daily intake of thiamin to 1.4 mg/day. This activity outlines the indications, mechanism of action, methods of administration, significant adverse effects, contraindications, and monitoring of vitamin B1 so providers can direct patient therapy in treatment or supplementation where it is indicated, as part of the interprofessional team.

Objectives:

• Identify the physiological role and mechanism of action of thiamine (vitamin B1).
• Describe the signs and symptoms of thiamine deficiency.
• Review appropriate dosing of thiamine for patients exhibiting deficiency.
• Outline interprofessional team strategies for improving care coordination and communication to properly use vitamin B1 to improve patient outcomes for indicated deficiencies.

Indications

Vitamin B1 is one of the eight B vitamins. It has acquired several names since its discovery, including aneurin and, as of the year 2000, thiamin (thiamine). Because thiamin can only be stored in the body for a short time before excretion, a regular dietary intake of thiamin is necessary to maintain proper blood levels. Moderate amounts of thiamin are present in most foods, yet the food sources richest in thiamin include whole-grains, brown rice, pork, poultry, soybeans, nuts, dried beans, peas, and fortified or enriched grain products such as cereals. The recommended daily intake (RDI) for adults over age eighteen is 1.2 mg/day for men and 1.1 mg/day for women. For children, adequate intake levels are lower, with RDI levels at 0.2 mg/day during early infancy that steadily increase with age. Women of any age who are pregnant or should increase their daily intake of thiamin to 1.4 mg/day.

Vitamin B1 deficiencies may occur if the required daily intake (RDI) is not maintained.; this can happen with alcohol abuse, poor nutrition, fasting, restricted access to food, persistent vomiting, and in cases where the absorption of thiamin becomes hindered. Additionally, individuals with excessive carbohydrate consumption may fail to compensate by increasing their level of thiamin intake, resulting in a thiamin deficiency since thiamin plays a role in carbohydrate metabolism.

Decreased thiamin levels can result in reduced enzymatic activity, altered mitochondrial activity, impaired oxidative metabolism, and reduced energy production. Many cells and organ systems can be affected, and cell death can occur. Neurons have high energy requirements and therefore are especially vulnerable to a thiamin deficit.

Wernicke-Korsakoff syndrome (WKS) and beriberi are the two most common complications that may arise from a thiamin deficiency, though these two syndromes rarely occur simultaneously in an individual. WKS affects the central nervous system, which involves the brain and spinal cord. Its most common cause is alcohol misuse, seen alongside poor nutrition, but can present in individuals who are at risk for thiamin deficiency. Technically, WKS consists of two different syndromes that can often present together. Wernicke encephalopathy occurs early in the disease course and characteristically demonstrates non-inflammatory brain lesions. It can present with ataxia, ophthalmoplegia, punctate hemorrhages in the brain, altered mental status, and balance abnormalities. If left untreated, Wernicke encephalopathy can eventually evolve to include Korsakoff psychosis. Individuals will now present with delirium and permanent memory loss. Treatment should commence emergently to prevent disease progression and irreversible brain damage. Empirically, WKS treatment is with at least 500 mg thiamine hydrochloride per 100mL of normal saline given over 30 minutes. This regimen should be repeated three times a day for 2 to 3 days. Thiamine administration should be before or alongside glucose.

Beriberi is another disorder caused by thiamin deficiency. It most frequently presents in people who abuse alcohol but also can be due to other etiologies resulting in thiamin deficiency. Early on, symptoms of beriberi are nonspecific and include constipation, appetite suppression, nausea, mental depression, fatigue, peripheral neuropathy, anorexia, and weight loss. With progression, chronic symptoms can begin to manifest as either wet beriberi or dry beriberi. Wet beriberi presents with edema, an enlarged heart, cardiac failure, warm extremities, pleural effusions, and pulmonary edema. Meanwhile, complications of dry beriberi are predominantly neurological, with peripheral nervous system involvement. Individuals with dry beriberi may have paresthesia, foot drop, muscle wasting, numbness, and absent ankle reflexes.[1][2][3]

Mechanism of Action

Like all B vitamins, vitamin B1 is water-soluble and gets absorbed directly into the blood from the gastrointestinal tract. Once absorbed into the circulatory system, thiamin can circulate freely without carrier molecules in plasma and red blood cells until it eventually gets excreted in the urine. While in the body, it can be stored in the liver, but only for a maximum of eighteen days. It can cross the blood-brain barrier.

Once absorbed into the blood, the thiamin diphosphotransferase enzyme converts thiamin from its provitamin form into its active form, thiamin pyrophosphate (TPP). This reaction requires magnesium as a cofactor. TPP is a coenzyme used for energy metabolism. It is an essential component of the following three reactions:

1. TPP is a cofactor in the E1 subunit of the pyruvate dehydrogenase (PDH) complex. The E1 subunit specifically converts pyruvate to hydroxyethyl-TPP and carbon dioxide. Meanwhile, the PDH complex as a whole decarboxylates pyruvate to convert it to acetyl-CoA while also generating nicotinamide adenine dinucleotide (NADH) in the process. NADH can later convert to ATP, a source of energy for cells. Ultimately, the acetyl-CoA produced can then proceed to enter the Citric Acid Cycle to generate additional ATP. Thus, the PDH complex, which requires thiamin as a cofactor, has a significant role in deriving energy from carbohydrate metabolism. Additionally, the PDH complex function is essential in the production of acetylcholine (a neurotransmitter) and myelin.
2. TPP is also used in the citric acid cycle as a cofactor in the alpha-ketoglutarate dehydrogenase reaction where alpha-ketoglutarate is decarboxylated to form succinyl-CoA. This reaction is essential in propagating the citric acid cycle, from which energy derives. Also, this reaction has a role in maintaining glutamate, aspartate, and gamma-aminobutyric acid (GABA) levels. GABA is an inhibitory neurotransmitter in the brain that prevents the over-excitation of neurons, thus preventing delirium.
3. TPP is required as a cofactor in the pentose phosphate pathway (PPP), specifically in the transketolase reaction. The PPP occurs within the cytosol of cells as an alternate pathway in carbohydrate catabolism, and its purpose is to provide nicotinamide adenine dinucleotide phosphate (NADPH) and ribose-5-phosphate. NADPH can then factor in several biochemical pathways such as in steroid, fatty acid, amino acid, neurotransmitter, and glutathione synthesis. Glutathione synthesis is particularly important because glutathione can reduce oxidative stress and free radical damage to cells. Meanwhile, ribose-5-phosphate is an essential building block in nucleic acids. However, if nucleic acids are not necessary in a cell, then ribose-5-phosphate can enter the non-oxidative phase of the PPP where transketolase and TPP are necessary to help transform ribose-5-phosphate back into glycolysis intermediates (such as glucose-6-phosphate). In this reaction, TPP is required as a cofactor to stabilize a two carbon carbanion intermediate.

Based on its role in these reactions, it is apparent that thiamin, in the form of TPP, is essential for energy production, cell viability, and proper neuronal functioning.[4][5][6][7]

Administration

Individuals at risk of acquiring a thiamin deficiency or individuals who have a non-emergent thiamin deficiency can be instructed to take 50 mg of thiamin by mouth daily or can be given an injection of 50 to 100 mg of thiamin three to four times daily. Oral thiamin supplements may be taken with or without food since food intake does not influence the absorption of vitamin B1. Thiamin supplementation is nontoxic, even in excess.

Adverse Effects

In individuals receiving Vitamin B1 supplementation, the most commonly reported adverse effects include sensations of warmth, urticaria, pruritus, angioedema, diaphoresis, cyanosis, and anaphylaxis.

Contraindications

Allergic individuals should avoid taking Vitamin B1 supplements to avoid a hypersensitivity reaction. Also, pregnant women should use thiamin with caution as the RDI of thiamin increases during pregnancy and lactation. Finally, some parenteral thiamin products may contain aluminum. Therefore, these products should be used with caution in individuals with renal impairments, particularly in premature infants, to avoid the accumulation of aluminum and subsequent aluminum toxicity.

Monitoring

The best way to measure thiamin levels in patients is with erythrocyte transketolase activity. Thiamin levels also can be obtained from blood and urine; however, these values fail to include the amount of stored thiamin that may be present in the liver. It is important to note that thiamin easily gets destroyed by heat. 

Enhancing Healthcare Team Outcomes

All healthcare workers should encourage healthy nutrition in their patients. Vitamin B1 deficiency is not common in North America but can occur in people with malabsorption syndrome, poverty, alcoholism, and restriction to food.

Because thiamin stores in the body are small, it quickly depletes if there is no regular intake. Moderate amounts of thiamin are present in most foods, yet the food sources richest in thiamin include whole-grains, brown rice, pork, poultry, soybeans, nuts, dried beans, peas, and fortified or enriched grain products such as cereals. The recommended daily intake (RDI) for adults over age eighteen is 1.2 mg/day for men and 1.1 mg/day for women. For children, adequate intake levels are lower, with RDI levels at 0.2 mg/day during early infancy that steadily increase with age. Women of any age who are pregnant or should increase their daily intake of thiamin to 1.4 mg/day.

Thiamin therapy should have the efforts of an interprofessional healthcare team behind it. All healthcare team members may make general supplementation suggestions, but for deficiency syndromes, therapeutic dosing will likely come from physicians, dieticians, or nutritionists. Pharmacists can also weigh in on appropriate supplementation, although there is almost no toxicity risk with thiamin. Nursing can verify compliance and also monitor treatment effectiveness. Thiamin therapy becomes optimized with the participation of the entire interprofessional healthcare team, including physicians, nursing, pharmacists, and nutritionists, and/or dieticians. Collaboration among all members will drive optimal outcomes. [Level V]

The outlook for patients with thiamine deficiency is good as long as the patient has not developed moderate to severe neurological and cardiac deficits. In most people, with thiamine supplementation, the outlook is good.[4][8][9][10] [Level V]

Thiamine – an overview | ScienceDirect Topics

XV. THIAMIN

A. Names Used Previously

Vitamin B1, oryzamin, anti-beriberi vitamin, antineuritic vitamin, torulin, polyneuramin, and aneurin are names previously applied to this vitamin. It is now called thiamin. Its use in phrases such as “thiamin activity” and “thiamin deficiency” is acceptable.

B. Deficiency in Horse Diets

Horses fed poor-quality hay have been shown to develop a thiamin deficiency (54). Horses poisoned by yellow star thistle (Centaurea solstitialia) causing glossopharyngeal (throat) paralysis recovered following 5–7 days administration of 1 g of thiamin daily (55). Supplemental thiamin is beneficial in the treatment of thiamin deficiencies resulting from bracken fern poisoning (56). A recent study (57) indicated that incoordination, staggering, and muscular tremors were observed in 27 mules, 2 months after introduction to bracken fern-infested pasture. Eight died and the rest recovered after removal from the pasture and injection with 100 mg of thiamin. At necropsy, generalized congestion, pulmonary edema, and serosal and mucosal hemorrhages were noted.

C. Effect of Deficiency

Experimentally produced thiamin deficiency causes anorexia (loss of appetite), loss of weight, incoordination (especially in the hind legs), lower blood thiamin, elevated blood pyruvic acid, and a dilated and hypertrophied heart (5, 54, 58, 59). A study involving the use of amprolium (a thiamin antimetabolite) to produce a thiamin deficiency resulted in bradycardia and dropped heart beats, ataxia, muscular fasciculations, and periodic hypothermia of peripheral parts (hooves, ears, and muzzle). Some of the horses exhibited blindness, diarrhea, and body weight loss (60).

D. Requirements

The 1989 NRC report (3) states that although research data are limited, on the basis of research with horses and other species the thiamin requirement appears to be no more than 1.36 mg per pound of diet dry matter for maintenance, growth, and reproduction, unless high levels of antithiamin compounds are consumed. For performance horses it may be prudent to ensure that their diets contain 2.47 mg per pound of diet dry matter. A Texas A & M study (61) suggested that the NRC-recommended allowance of 1.36 mg of thiamin per pound of diet may not be adequate for performing horses. Thiamin is synthesized by the horse and it is estimated that 25% of the free thiamin in the cecum is absorbed by the horse (5, 62). The exact thiamin requirement of the horse is not known. Tables 5.2, 5.3, 5.4, and 15.9 give suggested levels of thiamin to use in horse diets. In certain situations, such as the heavy stress of training, racing, or performance, thiamin supplementation may be beneficial.

E. General Information

There is limited storage of thiamin in the body, which indicates the horse needs a regular supply in the diet. Thiamin functions as a constituent of enzyme systems and is essential in the utilization of carbohydrates and protein. Thiamin plays a very important role in glucose metabolism. Since the breakdown of carbohydrates is increased during racing or performance, it is important that thiamin be available in sufficient quantity.

Thiamin toxicity in the horse has not been reported. This could be due to excess thiamin being rapidly excreted in the urine; however, excessive levels of thiamin in the diet should not be used. NRC (2) states that dietary intakes of thiamin up to 1000 times the requirement level are apparently safe for most animal species. So, oral toxicity in horses is very unlikely for thiamin (3).

Thiamin is heat labile, so excess heat or autoclaving can reduce the thiamin level in feeds.

Disease conditions as well as diarrhea and malabsorption may increase thiamin requirement. Endoparasites such as Strongylids and Coccidia compete with the host for thiamin contained in the feed (27).

Thiamin antimetabolites and thiaminases can cause a thiamin deficiency. Thiaminase splits the thiamin molecule and makes it inactive.

Symptoms, Causes, Diagnosis, and Treatment

Vitamins are essential nutrients that keep the body healthy, but it is possible to have too much of a good thing. Taking an excessive amount of any one vitamin can cause serious health problems, a condition generally referred to as hypervitaminosis, or vitamin toxicity. Certain diet choices may also risk regularly overconsuming vitamins. Misusing vitamin supplements can be very dangerous. Some medications can also increase the risk of vitamin toxicity, either by increasing the body’s absorption of a vitamin or by containing vitamin-based compounds.

In 2017, vitamins were responsible for 59,761 toxic exposures in the United States, 42,553 of which were in children under age 5, as listed by the National Poison Data System. Fortunately, the number of serious medical outcomes associated with vitamin toxicity is much lower. Nevertheless, it is important to recognize the symptoms and understand the causes of vitamin toxicity.

What Are Vitamins?

Vitamins are a group of essential nutrients vital to keeping your body healthy. The right amounts are important to maintain a healthy brain, bones, skin, and blood. Several vitamins also assist in metabolizing food. Many vitamins are not produced by the body and must be obtained through food or vitamin supplements, including:

• Vitamin A
• Vitamin B1 (thiamin)
• Vitamin B2 (riboflavin)
• Vitamin B3 (niacin)
• Vitamin B5 (pantothenic acid)
• Vitamin B6
• Vitamin B7 (biotin)
• Vitamin B9 (folate, folic acid)
• Vitamin B12 (cobalamin)
• Vitamin C (ascorbic acid)
• Vitamin D (calciferol)
• Vitamin E (alpha-tocopherol)
• Vitamin K (phylloquinone, menadione)

Fat-soluble vs. Water-soluble Vitamins

The main distinction that determines the danger of overdosing is whether a vitamin is fat- or water-soluble. Water-soluble vitamins are used by the body as they are digested and are not usually absorbed in any body tissues for a long period of time. All essential vitamins are water-soluble except for vitamins A, D, E and K. These four are fat-soluble, meaning the body can keep them stored within fat deposits for long-term use. 

Due to the way vitamins are absorbed and used by the body, some vitamins pose a lower risk of a one-time toxic dose. They only cause health problems when taken in high doses continuously for many days or in very extreme doses, usually from misuse of supplements. Fat-soluble vitamins are taken up by the body quickly and can pose immediate health risks when taken in moderate-to-extreme doses.

Multivitamins or vitamin supplements shouldn’t normally be taken in excess of their recommended daily dosage. While some diseases and conditions can be helped by elevated vitamin use, a healthcare professional should always be consulted before following high-dose vitamin regimens. 

For these reasons, care should be taken to use only the recommended amount of supplements. Let’s consider each of the vitamins and the potential risk of vitamin toxicity for each one.

Consider the most common vitamins and how toxicity may occur if an excessive amount of each is taken, including the potential symptoms, diagnosis, and treatments.

Vitamin A

Vitamin A is used by the body to promote vision, the immune system response, and normal organ function when consumed in moderate amounts. It is a fat-soluble vitamin found in high concentrations in animal liver, kidney, and fish oil, and in moderate concentrations in dairy and eggs. Vegetables such as sweet potatoes and carrots are also moderate sources of vitamin A. 

Animal-based foods contain preformed vitamin A that readily becomes usable by the body through digestion, while plant-based foods often contain carotenoids generically called provitamin A, which can be made into vitamin A in the liver.

The amount of vitamin A in a food or supplement is indicated by retinol activity equivalents (RAE), a measure of how readily the various provitamin A compounds, such as beta-carotene, become vitamin A used by the body. It may also be listed in international units (IU), but FDA regulations require product labels to list amounts in micrograms (mcg) RAE by 2021.

The recommended vitamin A from animal sources and retinoid-based supplements per day varies for different people:

• Men over age 18: 900 mcg RAE (3,000 IU)
• Women over age 18: 700 mcg RAE (2,333 IU)
• Pregnant women over age 18: Contraindicated in pregnancy
• Lactating women: 1,300 mcg RAE

Adults should avoid taking more than 3,000 mcg RAE (10,000 IU). Keeping daily vitamin A intake near the recommended amounts is the safest choice as chronically taking more can be harmful. Pregnant people should avoid ingesting Vitamin A supplements during pregnancy or while trying to conceive, as they can have teratogenic effects, which leads to developmental disturbances of the embryo/fetus.

Symptoms

Vitamin A toxicity commonly affects the skin, causing reddening, irritation, and patchy peeling. Chronic, excessive supplement use may lead to more severe symptoms, including:

These severe symptoms correspond to lasting effects on bone health and possible liver damage.

A unique symptom of excess beta-carotene consumption, called carotenodermia, causes a yellow or orange coloration of the skin, but this condition is not dangerous.

Causes

Excessive consumption of animal food sources, like liver or fish oil, in addition to supplements high in preformed vitamin A, increases the risk of vitamin A toxicity. Many multivitamins contain vitamin A as a mix of preformed vitamin A and provitamin A, so it is important to identify what kinds are present in these supplements. 

Plant-derived beta-carotene, a provitamin A found in carrots, is metabolized differently than preformed vitamin A. It is not found to be responsible for any of the serious symptoms of vitamin A toxicity.

Some medications will affect how the body absorbs vitamin A. Orlistat, a common weight loss medication, decreases the absorption of fat-soluble vitamins (including vitamin A). Patients taking orlistat should take individual liposomal forms of fat-soluble vitamins (A, D, E, K) to replenish what the medication strips from the body.

Medications called retinoids consist of vitamin A related compounds and are used for treating ailments affecting the skin, blood, and organ lining. These may increase the risk of toxicity when taken together with vitamin A supplements.

Treatment

If chronic vitamin A toxicity is diagnosed based on a blood test, the most important course of action is to reduce vitamin A intake. In cases of a large toxic dose, activated charcoal can be administered. If activated charcoal isn’t available, and a hospital can’t be reached within an hour, ipecac should be used to induce vomiting. In case of a vitamin overdose, poison control should always be contacted as soon as possible at (800) 222-1222.

B Vitamins

Most of the B vitamins are important for metabolism with functions linked to skin, hair, brain, and muscle health. Fortunately, with the exception of vitamins B3 and B6, significant vitamin toxicity is not associated with their overuse.

Vitamin B1 (Thiamin)

Vitamin B1, also known as thiamin, is found in beef, pork, whole grains, legumes, nuts, and sunflower seeds. The recommended daily amount for adults is 1.2 mg for men and 1.1 mg for women.

Vitamin B1 is not known to be toxic in high doses.

Vitamin B2 (Riboflavin)

Vitamin B2, also known as riboflavin, is found in dairy, eggs, meat, salmon, whole grains, and leafy greens. The recommended daily amount for adults is 1.3 mg for men and 1.1 mg for women.

Vitamin B2 has not been shown to be toxic in high doses.

Vitamin B3 (Niacin)

Vitamin B3, also known as niacin, is found in meat, fish, whole grains, and leafy greens. The recommended daily amount for adults is 16 mg for men and 14 mg for women.

Vitamin B3 is used therapeutically to manage cholesterol. However, people taking it may be at risk of toxicity when taking doses of 50 milligrams (mg) per day or more for a prolonged period of time. Make sure to check your cholesterol levels after 30-60 days of a niacin (B3) protocol.

Pregnant women should avoid taking too much vitamin B3 as it can cause birth defects.

High one-time doses of vitamin B3 are not known to be toxic. However, B3 is contraindicated in patients with gout as it can increase uric acid levels. And when used in combination with statins, there is a higher risk of myopathy and rhabdomyolysis. B3 may also cause worsening of peptic ulcer disease.

Early symptoms of vitamin B3 toxicity are sometimes called “niacin flush” due to vasodilation properties leading to reddening of the skin, itchiness, and burning. While harmless, it is an important indicator of vitamin B3 toxicity. Prolonged overuse of vitamin B3 can cause liver damage, particularly in people with pre-existing liver disease.

Vitamin B5 (Pantothenic acid)

Vitamin B5, also known as pantothenic acid, is found in chicken, egg yolk, dairy, whole grains, legumes, mushrooms, kale, cabbage, and broccoli. The recommended daily amount for adults is 5 mg. 

Vitamin B5 has not been shown to be toxic in high doses, but in extreme doses may cause diarrhea.

Vitamin B6

Vitamin B6 is a group of compounds related to pyridoxine found in poultry, pork, fish, whole grains, legumes and blueberries. The recommended daily amount is 1.3 to 2 mg for adults.

Supplemental doses over 100 mg per day are not recommended for adults outside of therapeutic applications. Extreme doses of 1,000 to 6,000 mg taken over an extended period of time can negatively affect the brain, creating neurological symptoms like numbness and tingling in the extremities. It may cause loss of coordination, skin lesions, and disrupted digestion. The symptoms usually resolve when the vitamin supplements are discontinued.

Vitamin B7 (Biotin)

Vitamin B7, also known as biotin, is found in liver, pork, eggs, dairy, banana, sweet potato, and nuts. The recommended daily amount for adults is 30 mcg. 

Vitamin B7 has not been shown to be toxic in high doses.

Vitamin B9 (Folate, Folic Acid)

Vitamin B9, commonly known as folate or folic acid, is important for new cell production as well as early brain and spine development of a fetus during pregnancy. It is found in citrus and leafy greens.

The recommended daily amount for adults is 400 mcg. Pregnant women should get 600 mcg and those who are lactating should get 500 mcg daily.

Folic acid is not generally toxic in high doses, but it can obscure symptoms of pernicious anemia.

Vitamin B12 (Cobalamin)

Vitamin B12, also known as cobalamin, is found in dairy, eggs, fish, poultry, and meat. The recommended daily amount for adults is 2.4 mcg. 

Vitamin B12 has not been shown to be toxic in high doses.

Vitamin C

Vitamin C, also known as ascorbic acid, is used by the body as an antioxidant to prevent damage to cells and also for the growth and repair of tissues in the body. It is found in citrus fruit, potatoes, peppers, and greens. The recommended daily amount for adults is 90 mg for men and 75 mg for women.

Vitamin C is not normally considered toxic, but large doses of 2,000 mg per day can affect digestion, causing diarrhea, cramps, and nausea.

Vitamin D

Vitamin D, also known as calciferol, assists calcium absorption and bone building. Pre-vitamin D can be produced in the skin, but with more people spending the majority of their time indoors or living at latitudes with seasonally reduced sun, sunlit skin alone may not provide all the vitamin D needed. Vitamin D is therefore found in many foods such as fortified milk, fortified juice, cereal, and fish and is available as a supplement.

The recommended daily amount for adults 31 to 70 years old is 15 mcg (600 IU) and 20 mcg (800 IU) for adults 71 and older.

Taking 100 mcg (10,000 IU) or more daily as vitamin D supplements may risk vitamin D toxicity, leading to abnormally high levels of calcium in the blood. Symptoms may include kidney stones, nausea, recurrent vomiting, constipation, excessive thirst, excessive urination, confusion and weight loss. It has also been connected to cancer risk, heart problems, and an increased risk of bone fractures.

Diagnosis may be done by blood and urine tests for calcium, vitamin D, and phosphorus. For treatment, stopping vitamin D intake is recommended, but other treatments may be needed in severe cases.

Vitamin E

Vitamin E, also known as alpha-tocopherol, is a group of eight related compounds used as antioxidants to protect the body’s cells from damage. It is found in fish, vegetable oil, nuts, seeds, wheat, and leafy vegetables.

The recommended daily amount for adults is 15 mg. 

Daily use of 300 mg or more from supplements may increase the risks of prostate cancer in men, stroke, and hemorrhages.

Vitamin K

Vitamin K, also known as phylloquinone and menadione, is a fat-soluble vitamin important for blood clotting. It is found in milk, soy oil, and leafy greens. Supplements are not generally needed except in situations where absorption is decreased.

The recommended daily amount for adults is 120 mcg for men and 90 mcg for women.

Avoid Vitamin K supplementation if you are taking, or plain to take, oral anticoagulants like Coumadin (warfarin), as they are antagonists.

A Word From Verywell

If you are concerned about vitamin toxicity, speak with your healthcare provider about your use of vitamin supplements. It will be possible to identify associated symptoms, and appropriate blood testing and, if needed, treatment can be arranged. As a general rule, simply stopping the overuse of supplements may allow the body to correct the imbalance and restore health.

Alcohol related thiamine deficiency – Alcohol and Drug Foundation

Thiamine

Thiamine, also known as vitamin B1, has a number of essential functions within the body. It is an important nutrient for taking energy from food and turning it into energy for the brain, nerves and heart. Thiamine is needed by the body to process fats and proteins – but it is most important for processing carbohydrates (sugars and starches).¹

Thiamine is naturally present in some foods, including:

• whole grain products such as cereals, rice, pasta, and flour
• wheat germ
• beef and pork
• trout and bluefin tuna
• eggs
• legumes and peas
• nuts and seeds.²

It is also added to some food products such as bread³ and is available as a dietary supplement.

While fruit, vegetables, and dairy products are not very high in thiamine, they can become a substantial source of thiamine when eaten in large amounts.²

Thiamine deficiency

Thiamine deficiency is common in drinkers who consume excessive amounts of alcohol. This is due to:

• poor nutrition and the diet not containing enough essential vitamins, and
• inflammation of the stomach lining due to excessive alcohol consumption, which reduces the body’s ability to absorb vitamins.⁴

Thiamine deficiency can cause:

• loss of appetite
• constipation
• fatigue and muscle weakness.

If a lack of thiamine persists, a condition called beriberi may develop over the following weeks or months.⁵ There are two types of beriberi – wet beriberi and dry beriberi. Wet beriberi affects the heart and circulatory system and in extreme cases can cause heart failure. Dry beriberi damages the nerves and can lead to decreased muscle strength and eventually, muscle paralysis. If untreated beriberi can be life-threatening.⁵

In extreme cases, beriberi is associated with Wernicke-Korsakoff syndrome. Wernicke encephalopathy and Korsakoff syndrome are two forms of brain damage caused by thiamine deficiency. Both are conditions due to brain damage which is often caused by excessive alcohol use.⁴

Wernicke–Korsakoff’s syndrome

Wernicke’s encephalopathy is a form of serious brain injury resulting from a lack of thiamine that most commonly occurs in alcohol-dependent people. It is not a withdrawal complication, but it is often identified in people undergoing alcohol withdrawal. It can co-exist with and should be distinguished from acute alcohol withdrawal, loss of brain function due to liver disease, and other causes of confusion.⁶

Wernicke’s encephalopathy is usually reversible, but if untreated or inadequately treated can lead to Korsakoff’s syndrome, a chronic and disabling condition characterised by severe short-term memory loss and impaired ability to acquire new information. It is important to remember that Korsakoff’s syndrome is not dementia or delirium.⁶

Symptoms of Wernicke-Korsakoff’s syndrome include:

• mental confusion
• paralysis of the nerves that move the eyes
• an impaired ability to coordinate movements particularly of the lower extremities.

If you are concerned about vitamin depletion as a result of drinking alcohol, talk to your health professional.

90,000 10 diseases caused by a lack of vitamins

Until recently, the effects of vitamins on human health were largely unknown. Renaissance researchers found that ships that consumed mostly salted meat and grains caused a wide variety of diseases. Almost all diseases could be cured by switching to a more varied diet. People began to suspect the presence of vitamins, tiny substances that are essential for maintaining good health.Nobel Prizes were awarded to scientists who correctly identified specific vitamins, and this allowed thousands of people to avoid death from vitamin deficiency simply by eating certain foods. Today, vitamin deficiencies continue to occur in developing countries or in countries dominated by restricted nutrition. But many centuries ago, people lived in fear of these deadly nutritional problems, the causes of which were unknown and seemed to affect people in a random order.

1. Beri-beri disease (vitamin B1 deficiency)

Polyneuritis (beriberi, rice sickness, vitamin deficiency) is a disease characterized by the following symptoms: weight loss, weakness, pain, brain damage, heart rhythm disturbances and cardiac failure. If vitamin deficiency is not treated, the disease is fatal. For a long period of time, it was an endemic (widespread) disease in Asia. Oddly enough, vitamin deficiency was observed almost exclusively among the wealthy members of society, and did not occur among the poor.Doctors were puzzled why wealthy people, eating abundant and fresh food, became victims of vitamin deficiency, because vitamin deficiency occurred with a deficiency of nutrients, while the poor, eating very poor food, did not suffer from vitamin deficiency. As it turned out, vitamin deficiency is a deficiency of vitamin B1 (thiamine), which is found in the husk of rice grains. The rich washed the rice so well that the hulls with vitamin B1 were washed off completely, while the poor did not rinse the rice and consumed enough vitamin B1.White bread can potentially cause vitamin deficiency, so today developed countries add vitamin B1 to white bread. Avitaminosis is currently found mainly in alcoholics, whose health is too weakened to absorb enough vitamin B1.

2. Pellagra (vitamin B3 deficiency)

After the discovery and development of America, settlers began to grow corn, and subsequently it spread throughout the world. Native Americans, who ate corn since childhood, cooked it with lime added, but the taste was unpleasant for Europeans, and they eliminated lime from the corn-making process.Corn crops expanded and pink disease began to spread as well. Symptoms of the disease such as diarrhea, dermatitis, dementia were fatal. Many people believed that corn was somewhat toxic and could not explain the absence of disease among the indigenous people of the New World. After thousands of deaths, it was discovered that corn, although high in carbohydrates, did not have enough vitamin B3 (niacin). Farmers who often ate only one bread were susceptible to this disease.Native Americans actually use lime as a source of vitamin B3. Today it is well known that by eating a variety of foods, you get enough vitamin B3, and rose disease is easily treated.

3. Deficiency of biotin (vitamin B7)

Deficiency of biotin is caused by a lack of vitamin B7 (biotin). It causes rashes, hair loss, anemia, and mental health problems including hallucinations, drowsiness, and depression. Vitamin B7 is found in meat, liver, milk, peanuts, and some vegetables.Biotin deficiency is rare, however, there has been a small spike in the number of cases where the idea of ​​eating raw eggs was popular among bodybuilders. One of the proteins found in raw egg white binds vitamin B7 and makes it difficult to digest, resulting in a deficiency. Cooking egg whites renders this protein inactive. Mild biotin deficiency occurs in about half of all pregnant women, due to the higher intake of vitamin B7 in the body during pregnancy, there are supplements by the World Health Organization that are recommended for these women.

4. Scurvy (vitamin C deficiency)

Scurvy has been reported among people who have been at sea for a long time. Ships, as a rule, took on board mainly long-term products, such as salted meat and dried grains, so the sailors ate very few fruits and vegetables, and often did without them. Scurvy causes lethargy, blemishes, bleeding gums, tooth loss, and fever. Scurvy is fatal. Ancient sailors could cure scurvy with various herbs.In later times, these ancient medicines were not used and their benefits in treating scurvy were forgotten. In the 18th century, horse meat and citrus fruits were discovered to help treat scurvy, and British sailors consumed so much lime that they were nicknamed “limeys”. These foods are now known to contain vitamin C, and today scurvy is rarely fatal as it once was. Today there are groups of people who advocate megadoses of vitamin C, which are hundreds of times higher than the recommended daily requirement.No positive results have been documented, however, there is evidence that overdose is possible, which can be harmful to health.

5. Rickets (vitamin D deficiency)

Rickets causes muscles and bones to become soft, which can cause permanent muscle and bone deformation in children. Rickets is most common in children and babies who are poorly nourished or do not leave the house for a long time, but now rickets is relatively rare in developed countries.Breastfeeding babies are at greater risk if they or their mothers do not get enough sunlight and baby food is now available to prevent rickets. Rickets is caused by a deficiency of vitamin D and calcium. Vitamin D is essential for proper absorption of calcium when it enters the bones for their strength and development. Adults rarely get rickets because their bones don’t grow and they don’t need a lot of calcium. Vitamin D enters the body from many foods, but the body can only use it if it has been converted to its active form using sunlight.In recent years, there has been a slight increase in the number of children with rickets, possibly due to the fact that too many of them stay at home for long periods of time.

6. Vitamin B2 deficiency

This disease is present mainly in people who are malnourished and in alcoholics. The disease has characteristic features such as a hot pink tongue, chapped lips, swelling of the larynx, bloodshot eyes, and low red blood cells. Ultimately, this can cause coma and death.The disease is caused by a lack of vitamin B2 (riboflavin), but it is easily treated by eating foods rich in vitamin B2, including meat, eggs, milk, mushrooms, and green leafy vegetables. Vitamin B2 is also used as an artificial color (orange) in foods. It is absorbed into the bloodstream through the liver, so although an alcoholic can eat enough food rich in B2, he will not be able to use it. A real deficiency of vitamin B2 is quite rare, but about 10% of people in developed countries live in a state of mild deficiency, it is believed that this is due to a diet consisting of highly processed foods.Persistent small vitamin B2 deficiencies can increase the risk of minor health problems.

7. Vitamin K deficiency

Vitamin K deficiency occurs in half of all newborns worldwide. In severe cases, this causes uncontrolled bleeding and underdevelopment of the face and bones. In many hospitals, newborns are given vitamin K injections to avoid more severe symptoms. Unfortunately, babies born outside the hospital are statistically much more deficient in vitamin K.Vitamin K is found primarily in green leafy vegetables, although gut bacteria in the human body help produce some of it. Newborns do not yet have gut bacteria, so they are especially susceptible to vitamin K deficiency. In addition to newborns, vitamin K deficiencies are seen in dietary bulimic alcoholics and people with serious illnesses such as cystic fibrosis. Adults who bruise or bleed much more profusely than a normal person at the slightest injury have a vitamin K deficiency, which in itself may indicate one of the more serious illnesses or disorders.

8. Vitamin B12 deficiency

Vitamin B12 deficiency (Hypocobalaminemia) was first noticed as a sign of an autoimmune disease. Vitamin B12 deficiency leads to a gradual deterioration of the spinal cord and a gradual deterioration in brain function, which leads to loss of sensory or motor activity. Mental disorders with progressive brain damage begin as fatigue, irritability, depression, or memory loss.As the disease progresses, over the course of several years, psychosis and various manias may appear. This disease is irreversible and is caused by vitamin B12 deficiency. Fortunately, this vitamin is easily found in meat, dairy products, and eggs. Vitamin B12 is stored in the liver and can be consumed for years before it becomes deficient. Vitamin B12 deficiency is most common in developing countries among people who eat few animal products. In developed countries, vegans are at risk because plants do not have enough vitamin B12 for the human diet.Children need much more vitamin B12 than adults because they are growing up, so babies who are breastfed may be deficient in vitamin B12 and, as a result, may suffer permanent brain damage if their mother is deficient in vitamin B12. … Supplements are recommended for all types of diets and are the easiest way to avoid the devastating effects of this disease.

9. Paresthesia (vitamin B5 deficiency)

Vitamin B5 is found in almost every food, and vitamin B5 deficiency occurs in people who have fasted or volunteered in certain medical studies and people on a restricted diet with very little food …Lack of vitamin B5 causes chronic paresthesia. Paresthesia is very similar to the feeling of numbness that we sometimes experience when they say “goose bumps” or when limbs are “numb.” This kind of feeling is completely normal, but with a deficiency of vitamin B5 it happens all the time. Exhausted prisoners of war sometimes reported tingling and burning sensations in the hands and feet, now believed to be signs of paresthesia. This disease is virtually non-existent today and therefore most vitamin supplements do not include B5.

10. Night blindness (vitamin A deficiency)

Even the ancient Egyptians and Greeks wrote about night blindness (nyctalopia – nyctalopia). This disease prevents seeing at dusk, and sufferers of this disease become completely blind when night falls. The Egyptians discovered that they could cure those suffering from this disease by including in their diet liver, which contains high amounts of vitamin A, a deficiency of which causes night blindness. Vitamin A deficiency still affects one third of all children on earth under the age of five, with the result that more than half a million people suffer from the disease every year.The highest doses of vitamin A can be obtained from the liver, which in turn is very dangerous in case of an overdose, and can lead to various complications. In the past, starving Antarctic explorers ate dogs but became sick when they ate too much liver. Vitamin A is found in carrots, which has a slightly different variant of vitamin A compared to that found in the liver, and is non-toxic in high doses, although it can cause irritation and yellowing of the skin.During World War II, the Allies stated that they ate carrots to see well, but carrots only help to maintain normal vision, not improve it. In fact, they misled the enemy in order to hide the development of the military radar.
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Nutritionist explained why vitamin B1 deficiency is dangerous

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Nutritionist explained why vitamin B1 deficiency is dangerous

Nutritionist explained why vitamin B1 deficiency is dangerous

Memory degraded? Lethargy or chronic stress? Difficulty concentrating or collecting your thoughts? It is possible that you are deficient in vitamin B1.What’s with this … Sport RIA Novosti, 11.03.2021

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Memory degraded? Lethargy or chronic stress? Difficulty concentrating or collecting your thoughts? It is possible that you are deficient in vitamin B1.Nutritionist Olga Korableva explains what to do with this. Tonic for the nervous system If B1 (thiamine) is not enough, the nervous system suffers first. Thiamine is an important participant in carbohydrate metabolism: it suppresses lactic acid (the so-called fatigue toxin), which accumulates in the body and destroys nerve fibers. Therefore, the first symptoms of B1 deficiency are the so-called bare nerves: irritability and fatigue, insomnia and depressive conditions. Norm for a day The daily requirement of vitamin B1 for an adult is 1.5 milligrams.For pregnant women, the dosage is higher – 1.7 milligrams. But it should be borne in mind that these values ​​are close to ideal – if you have dysbiosis, stomach diseases, you drink alcohol and smoke, then you are at risk: thiamine will be absorbed three times worse. Acute deficiency of vitamin B1 is rare, but the consequences can be really unpleasant: neuropathy, low muscle tone, heart failure. Proper nutrition: menu with B1 Since thiamine is soluble in water, it does not accumulate in the body – therefore, foods with vitamin B1 should be on table every day.Thiamine is found in any plant, the only question is the degree of saturation. Most of all vitamin B1 is in pine nuts, sunflower seeds, pork, peanuts. If you are taking vitamin B1 in addition, you should not drink it with tea or coffee – this interferes with the absorption of thiamine. In addition, coffee provokes the release of hydrochloric acid, which inhibits the action of B1. Too much vitamin? An excess of B1 is possible only if a person undergoes a long course of injections – it can manifest itself as redness on the skin, and in a more severe case – in the form of allergic urticaria …Thus, if we are not talking about medicines, one should not be afraid of an overdose of the vitamin: thiamine, which the body receives from food, is excreted from the body through the kidneys. Nevertheless, you should not prescribe yourself B1 on your own – it is best to take a blood test and consult a doctor.

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vitamins, health

Memory deteriorated? Lethargy or chronic stress? Difficulty concentrating or collecting your thoughts? It is possible that you are deficient in vitamin B1. Nutritionist Olga Korableva explains what to do about it.

Tonic for the nervous system

If B1 (thiamine) is not enough, the nervous system suffers first. Thiamine is an important participant in carbohydrate metabolism: it suppresses lactic acid (the so-called fatigue toxin), which accumulates in the body and destroys nerve fibers.Therefore, the first symptoms of B1 deficiency are the so-called bare nerves: irritability and fatigue, insomnia and depression.

“Apathy, lethargy, bad mood, low concentration of attention – it is not customary in society to pay attention to this. People write off everything on their way of life, they think that they are just tired. They say something like:” I can’t get myself together, everything is forever I forget “, – comments Olga Korableva. – In fact, there is a high probability that the reason is commonplace – vitamin deficiency, which affects all systems of the body.For example, the task of thiamine is to ensure the transmission of nerve impulses, to supply the brain with glucose – the material for work. Therefore, if a blood test reveals a lack of vitamin B1 and you drink the drug, you will notice how your quality of life will increase. ” vitamin B1 for an adult is 1.5 milligrams, for pregnant women the dosage is higher – 1.7 milligrams.But it should be borne in mind that these values ​​are close to ideal – if you have dysbiosis, stomach diseases, you drink alcohol and smoke, then you are at risk: thiamine will be absorbed three times worse.

Acute vitamin B1 deficiency is rare, but the consequences can be really unpleasant: neuropathy, low muscle tone, heart failure.

Proper nutrition: menu with B1

Since thiamine dissolves in water, it does not accumulate in the body – therefore products with vitamin B1 should be on the table every day.Thiamine is found in any plant, the only question is the degree of saturation. Most of all vitamin B1 is in pine nuts, sunflower seeds, pork, peanuts.

“You can and should eat porridge – oatmeal, buckwheat, millet,” says Olga Korableva, “vegetables: onions, carrots, tomatoes, beets, potatoes. These are all affordable products that are in any store. But keep in mind that thiamine is destroyed when heating or freezing, so fresh vegetables are healthier anyway. Canned vegetables still have 40% of their original B1 levels. “

December 28, 2019, 09:00 hOZhHow to fill the deficiency of vitamin D: advice from an endocrinologist

If you take vitamin B1 in addition, you should not drink it with tea and coffee – this interferes with the absorption of thiamine. In addition, coffee provokes the release of hydrochloric acid, which inhibits the action of B1.

Too much vitamin?

Excess B1 is possible only if a person undergoes a long course of injections – it can manifest itself as redness on the skin, and in a more severe case – in the form of allergic urticaria.

Thus, if we are not talking about medicines, you should not be afraid of an overdose of vitamin: thiamine, which the body receives from food, is excreted from the body through the kidneys. Nevertheless, you should not prescribe yourself B1 on your own – it is best to take a blood test and consult a doctor.

Vitamin B1 (thiamin). Vitamins for a healthy lifestyle, vitamin and mineral complexes for your health and longevity.

Daily requirement

Norms of physiological need for vitamin B ₁ depending on age in Russia [MR 2.3.1.2432-08]

The upper permissible level of vitamin B intake ₁ for adults is 5 mg per day (“Unified Sanitary and Epidemiological and Hygienic Requirements for Goods Subject to Sanitary and Epidemiological Supervision (Control)” of the EurAsEC Customs Union).

The need for thiamine depends on a number of factors in the external and internal environment, in particular, on the nature of the diet.

Proteins of high biological value have a thiamine-preserving effect. They can reduce the need for thiamine. There have been cases of acute thiamine deficiency caused by protein starvation.

An excess of carbohydrates in food, on the contrary, increases the consumption of thiamine, especially in the child’s body.

The need for a vitamin is influenced by the level of physical activity.

The need for thiamine, in addition to significant physical exertion, is influenced by great neuropsychic stress. The following factors and conditions are also of greatest importance: pregnancy (especially with toxicosis), lactation, diseases of the gastrointestinal tract with malabsorption, diabetes, alcoholism, various infections and states of intoxication.

Vitamin B1 (thiamin)

What does vitamin B1 do?

In the body, thiamine joins two molecules of phosphoric acid and turns into thiamine diphosphate or cocarboxylase.Thiamine diphosphate is included as a coenzyme in the composition of the most important enzymes of carbohydrate, energy metabolism. The need for energy is the primary need of every living being. Without constant production and consumption of energy, no biological function of the body can be carried out.

Vitamin B1-dependent enzymes containing thiamine diphosphate in their active catalytic center “work” at intermediate stages of energy metabolism. They ensure the oxidation and use of energy of the residues of acetic and pyruvic acids formed during the oxidative breakdown of carbohydrates, primarily glucose, and fats.Insufficient energy supply to the body is one of the causes of muscle and heart weakness in vitamin B1 deficiency, which is so clearly manifested in patients with “take-take”.

With the most active participation of vitamin B1, acetylcholine is synthesized – a substance that plays an extremely important role in the transmission of nerve impulses. That is why in the picture of vitamin B deficiency, the leading place is taken by symptoms indicating a violation of the functions of the nervous system. These symptoms include changes in mood, skin sensitivity, sleep disturbances, memory disorders, paralysis, and seizures.Other consequences of B1-avitaminosis are severe disturbances in the activity of the heart, digestive organs, general depletion of the body (cachexia).

Where can you find vitamin B1?

The main source of vitamin B1 is wholemeal bread. But in white bread made from premium flour, that is, finely ground, thiamine is 5–10 times less. As with rice, it is removed when white flour is cooked along with the bran. Legumes are relatively rich in thiamine: peas, beans, lentils, soybeans, as well as buckwheat and oatmeal.In semolina, pasta and noodles it is almost absent. Lean pork, liver and kidneys contain the highest amount of vitamin B1 of meat products. Beef, fish, eggs and milk are very low in thiamine.

How much vitamin B1 do you need?

The human body should receive 1.2–2.1 mg of vitamin B1 per day. The need for it increases with frequent alcohol consumption, during pregnancy and lactation, and when taking antibiotics.

Lack and excess of vitamin B1.

A slight lack of vitamin B1 in the diet increases cravings for sugary foods and often causes a lack of appetite. More serious, it can lead to a condition called beri-beri (manifested by fatigue, weight loss and bloating).

Vitamin B1 is non-toxic. A significant overdose can cause allergic reactions and a drop in blood pressure.

Vitamin B1 is found in the following medicines:

Vitamin B1 is found in the following dietary supplements:

90,000 Hypovitaminosis – what is it

Hypovitaminosis is a disease caused by insufficient intake of one or more vitamins from food.Vitamin deficiency in diets is rare in developed countries, but is still common in some developing countries. A lack of vitamins is usually combined with a lack of essential nutrients. Vitamin deficiency can be categorized as primary or secondary. The primary deficiency is caused by poor nutrition. In a secondary deficiency, the recommended amount of vitamins may be ingested, but due to some problems such as gastrointestinal upset, malabsorption (malabsorption syndrome), certain medications, allergies, metabolic diseases, the nutrient is not absorbed and / or metabolized ineffectively.

Regardless of the reason, a sufficiently long-term deficiency of vitamins leads to a gradual loss of their reserves by the body. A full-fledged vitamin deficiency does not develop overnight. One of the earliest consequences of deficiency is a decrease in the level of excretion of the vitamin or its metabolite in the urine and / or a decrease in plasma levels. Thus, determining the level of vitamin in plasma or urine is one of the ways to assess the vitamin status of a person. If the deficiency continues, tissue levels of vitamins are gradually depleted and the enzymes (or functions) that depend on the vitamins will be less active, leading to organ and tissue damage and disease.

Minimum Daily Requirements have been established for vitamins and other nutrients to protect ordinary healthy people of specific age and sex groups from deficiencies. The daily requirement is set for each vitamin at the level below which deficiency symptoms appear. Recommended Daily Values ​​are the levels of essential nutrients that are considered sufficient to meet all nutritional needs in healthy individuals. For example, for vitamin D this level is 200 IU, for vitamin A – 800 μg, for vitamin C – 60 mg, for niacin (vitamin B3) – 18 mg, for vitamin E – 10 mg, for vitamin B6 – 2 mg, for vitamin B12 – 1 mg.

According to various estimates, more than a third of the world’s adult population takes vitamin supplements. A properly balanced diet contains sufficient amounts of all nutrients, including vitamins, but in some cases, vitamin supplementation is warranted. Increased requirements for vitamins are observed in pregnant and lactating women, people adhering to a low-calorie diet, strict vegetarians who have completely excluded meat and dairy products from their diet, as well as in some diseases, taking certain medications and in some other cases.

Some vitamins, especially the fat-soluble vitamins A and D, can be toxic. Taking too much vitamin A can lead to headaches, vomiting, etc. Although water-soluble vitamins are generally less toxic than similar amounts of fat-soluble vitamins, they can also have adverse effects on humans. High levels of the vitamin or its metabolite can interfere with the normal absorption of other nutrients.

There are natural as well as synthetic substances that interfere with the biological functions of vitamins.They can be natural food ingredients or medicines. These substances – antivitamins or vitamin antagonists – can cause deficiency symptoms similar to those observed in the absence / deficiency of the corresponding vitamin. At the same time, the additional intake of the vitamin eliminates the symptoms of deficiency. For example, isoniazid, a drug used to treat tuberculosis, can cause niacin and vitamin B6 deficiencies.

Antivitamins usually work as follows:

– they can break down the vitamin and render it inactive.Some foods (such as raw freshwater fish) contain the enzyme thiaminase, which breaks down vitamin B1;

– they can form a complex with a vitamin, as happens between avidin, which is present in raw egg white, and biotin;

– they can occupy the receptors for vitamins. For example, dicumarol, a structural vitamin K antagonist, occupies the appropriate receptors and prevents blood clots.

In recent years, in order to prevent and combat hypovitaminosis, fortification of food with vitamins has become a common practice.Vitamins are added to compensate for losses that occur during the processing and processing of food raw materials, or to fortify foods that are initially low in vitamins. Flour, breakfast cereals, and milk are examples of the most commonly vitamin-fortified foods.

Vitamin B1 (thiamin)

STYLAB offers test systems for the determination of thiamine (vitamin B ₁ ) in food, animal feed and pharmaceuticals by microbiological analysis.

Thiamine, or vitamin B ₁ is a sulfur-containing water-soluble substance. The old name for thiamine – aneurin – reflects the symptoms that occur when this vitamin is deficient in food. Its vitamin deficiency leads to neurological disorders. Vitamin B ₁ is essential for the normal development and life of the body. Its active form – thiamine pyrophosphate – is a coenzyme of several enzymes involved in the metabolism of proteins, fats and carbohydrates. In yeast, this substance regulates the first stage of alcoholic fermentation.There are other thiamine phosphates, as well as adenosine thiamine phosphates, but their role has not yet been studied.

Vitamin B ₁ is produced by some bacteria, fungi and plants. Animals, including humans, should receive this substance with food. Foods such as yeast and pork are high in thiamine, as well as many grains, flaxseeds, sunflower seeds, asparagus, cauliflower and some others. Freshwater fish, seafood, fern sprouts contain thiaminase – an enzyme that destroys vitamin B ₁ .Tea and coffee interfere with its absorption. Thiamine deficiency occurs in people with diabetes mellitus, diseases of the gastrointestinal tract, and alcoholism.

Lack of thiamine leads to various damages of the nervous, cardiovascular and digestive systems. With a slight deficiency of vitamin B ₁ , this is weakness, irritability, partial confusion and weight loss. Avitaminosis can manifest itself as beriberi disease, Korsakov-Wernicke syndrome, optic neuropathy.Beriberi comes in four forms. Symmetrical damage to the nervous system is characteristic of “dry” beriberi: decreased sensitivity, motor skills and reflexes. “Wet” beriberi manifests itself in the form of confusion and disorders of the cardiovascular system, up to heart failure. Infantile beriberi can manifest as aphonia, pseudomeningitis, or heart disease. In 2004, gastrointestinal beriberi was identified. Its symptoms are nausea, vomiting, abdominal pain, and lactic acidosis.The connection between beriberi and vitamin deficiency has been suggested since 1884. In 1897, Christian Eikman experimentally confirmed the connection between beriberi and eating polished rice. In 1911, Casimir Funk isolated thiamine in its pure form from rice bran. It was the first water-soluble vitamin to be isolated.

Korsakoff-Wernicke syndrome occurs with prolonged alcohol abuse, malnutrition or brain damage. With this disease, a person remembers past events, but cannot remember current ones.This leads to disorientation in time and space. Lack of thiamine can lead to coma or death.

With intravenous, subcutaneous, intramuscular and, in rare cases, with oral administration of high doses of thiamine, allergic reactions may occur, including Quincke’s edema and anaphylactic shock. Hypervitaminosis of vitamin B ₁ can lead to a decrease in blood pressure, bradycardia (slow heartbeat), as well as impaired absorption of certain minerals and a deficiency of vitamin B ₆ .

In the Russian Federation and the countries of the Customs Union, the content of thiamine in food products is regulated by TR CU 027/2012 “On the safety of certain types of specialized food products, including dietary therapeutic and preventive dietary nutrition” and TR CU 033/2013 “On the safety of milk and dairy products “. You can find the latest legislation on the website compact 24. com .

For the determination of thiamine in food, animal feed and medicines, a microbiological method of analysis is used.The VitaFast® Vitamin B1 (Thiamin) test system is a microplate coated with the microorganism Lactobacillus fermentum , whose growth depends on the presence of vitamin B ₁ in the medium. The concentration of thiamine is estimated using spectrophotometry at a wavelength of 610-630 (or 540-550) nm. The microbiological method for the analysis of vitamin B ₁ is simpler than chromatographic and does not require special equipment.

Literature

1. Encyclopedia of Medicines and Pharmacy Products RLSNET
2. Jane Higdon.Thiamin. Micronutrient Information Center, Linus Pauling Institute
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Medicinal liver damage induced by intake of vitamins A and E uMEDp

According to DILIN (Drug Induced Liver Injury Network), drug-induced liver injury (DILI) has increased markedly as a result of the use of vitamin supplements by people leading a healthy lifestyle.The greatest danger is the uncontrolled use of drugs in high doses, which can lead to toxic liver damage. DILI can be associated, among other things, with the intake of high doses of vitamins A and E. The article presents literature data on DILI caused by the use of drugs and dietary supplements containing vitamins A and E. The results of a number of studies demonstrate an increase in the level of hepatic transaminases, the development of non-cirrhotic portal hypertension , hepatitis and cirrhosis of the liver with hypervitaminosis A, severe liver damage leading to transplantation.A high risk of developing hemorrhagic stroke and even an increase in mortality from various causes are associated with hypervitaminosis E, especially with the combined use of high doses of both vitamins. A rare case of DILI associated with uncontrolled intake of high doses of the combined vitamin preparation Aevit was analyzed. A 23-year-old woman with no alcohol history with edematous-ascitic syndrome, hepatodepression syndrome without jaundice took Aevit 15 capsules daily for two years.The disease debuted with the appearance of edematous-ascitic syndrome. A thorough study ruled out viral hepatitis (A, B, C and E), autoimmune, toxic, ischemic and metabolic etiology, in particular Wilson’s disease. Aevitis was identified with a high degree of probability as the etiological factor of DILI. Based on the results of liver biopsy, chronic focal lobular hepatitis of drug etiology was diagnosed. Diagnosed with non-cirrhotic portal hypertension caused by vitamin A hypervitaminosis.

Fig. 1. Medicinal hepatitis – hypervitaminosis A. The cytoplasm of Ito’s cells is overflowing with lipid vacuoles containing vitamin A. Staining with hematoxylin and eosin (500-fold increase)

Fig. 2. Medicinal hepatitis – hypervitaminosis A. Perisinusoidal fibrosis – thin bundles of collagen fibers are deposited along the borders of the hepatic beams. Van Gieson picrofuchsin staining (500x magnification)

Introduction

Medicinal liver damage (DIL) is one of the most common causes of liver dysfunction [1, 2].Hepatotoxic properties and clinical manifestations in the form of hepatic cytolysis, which characterize modern drugs, and there are more than a thousand of them, lead to liver failure [1-4].

In 2016, the World Health Organization’s international database for monitoring drug side effects (Vigi Base) contained 13,208,000 Individual Case Safety Report (ICSR) reports [5-7] …

In European countries and the United States, DILI is observed on average in 15 out of 100 thousand patients using drugs (MP) [2, 8]. Acute hepatitis and liver failure develop in 10% of cases of DILI [1, 8]. According to the results of prospective studies, a chronic course is observed in 7-14% of DILIs, mortality rates or organ transplantation rates vary from 3.7 to 11% [9-11].

DILI can be caused by the use of not only drugs, but also herbal and multivitamin biologically active additives (BAA) [12-14].The effectiveness of dietary supplements is highly questionable. Nevertheless, they are popular among the population. The number of registered liver injuries as a result of their use increases annually [14-16]. According to a number of DILI registries, the proportion of such DILIs ranges from 2 to 20% of all detected cases [17–19].

There is no consensus on the use of a number of vitamins. Meanwhile, their use by persons of both sexes leading a healthy lifestyle is increasing [14, 16]. Doctors and patients underestimate the possibility of developing a hepatotoxic effect due to uncontrolled intake of vitamins [14, 16].

Many studies have demonstrated the individual characteristics of the hepatotoxicity of Ayurvedic and Chinese herbs, green tea, herbalife, including vitamins A and E [20–23]. Fat-soluble vitamins A and E are more often regarded as antioxidants that inhibit reactions that prevent the formation of free radicals that damage cell membranes [24–26]. However, against the background of a violation of the intake regimen or failure in the hepatobiliary system, they have a toxic effect on the liver [25–27].An overdose of these vitamins is considered more dangerous in the presence of acute and chronic diseases of the gastrointestinal tract, in particular the liver [27, 28]. Of the side effects of an overdose of vitamin E, it should be noted that it has a depressing effect on the blood coagulation process and, as a result, possible bleeding [26].

In a number of studies, as a result of an overdose of vitamin A, patients developed DILI in the form of hepatitis, non-cirrhotic portal hypertension (PNH), and liver cirrhosis [26-28].

G. Bucciol et al. in 2018 and T. Mounajjed et al. in 2014, the development of PNH in hypervitaminosis A was explained by obliteration of the Disse space as a result of hyperplasia and hypertrophy of stellate cells stimulated by lipid vacuoles of their cytoplasm that accumulate retinol [29, 30]. Further activation of Ito cells can lead to their transformation into myofibroblasts with the production of large amounts of collagen and the development of perisinusoidal fibrosis of the liver with the formation of cirrhosis [30, 31].Intracellular retention of vitamin A contributes not only to the progression of fibrosis, but also to the development of carcinogenesis [30, 31].

In hypervitaminosis E, increased mortality was recorded for various reasons [32, 33]. The severity of liver damage as a result of combined hypervitaminosis A and E varies from mild hepatitis to acute liver failure requiring transplantation [34, 35].

Vitamin A (retinol and other retinoids) is the main component for the functioning of the retina of the eye, since it forms the visual purple rhodopsin, which is necessary for visual adaptation in the dark [20, 28].Vitamin A plays the role of a cofactor in various biochemical processes, increases the mitotic activity of epithelial cells, and also prevents hyperkeratosis through RNA synthesis and sulfated mucopolysaccharides [20, 21, 28]. Retinol is absorbed in the small intestine with the participation of bile acids. From the intestine, it enters the liver, where about 90% is deposited in stellate cells. The daily requirement for vitamin A in an adult is about 3000–3500 IU [26, 28].

The function of vitamin E (alpha-tocopherol) is not fully understood.The structure of vitamin E makes it a highly effective antioxidant, it inhibits free radical reactions, prevents the formation of peroxides that have a damaging effect on cell membranes, which ensures the functioning of the nervous and muscular systems [22–34]. Alpha-tocopherol, being inside the phospholipid layer of cell membranes, protects cell membranes from oxidation by free radicals [24]. Together with selenium, it inhibits erythrocyte hemolysis, is a cofactor of some enzyme systems – it restores capillary blood circulation and increases tissue resistance to hypoxia [23].

Vitamin A hepatotoxicity

In 1937 the Swiss chemist R. Karrer was awarded the Nobel Prize in Chemistry for his work “Investigation of carotenoids and flavins”, as well as for the study of vitamins A and B ₂ [36]. In clinical practice, vitamin A is used to treat and prevent deficiency. High doses of fat-soluble vitamins contain many dietary supplements that are usually used uncontrollably by the population. As a result, there is an increase in the incidence of chronic intoxication with fat-soluble vitamins [22, 34].In the United States alone, 10–15 cases of such chronic intoxication are reported annually [8–10].

Severe liver damage as a result of chronic intoxication develops with the use of high doses of vitamin A (> 40,000 IU / day for several years) or ultra-high doses for a short period (> 100,000-200,000 IU / day for days / weeks) [ 26, 28]. About 90% of total vitamin A is found in the liver, mainly in stellate cells, which tend to be activated, acquiring a myofibroblast-like phenotype and producing a large amount of extracellular matrix [31].

The histopathological picture in liver diseases caused by the use of vitamin A is characterized by hyperplasia of hepatic stellate cells with the presence of large, lipid-filled vacuoles in the cytoplasm of cells by electron microscopy, and obliteration of the Disse space with collagen deposits, which causes portal hypertension [29, 30].

Several authors have found histological similarities between vitamin A-induced liver disease and primary biliary cholangitis.This made it possible to recommend ursodeoxycholic acid as a therapy for cholestatic types of liver damage [37].

Several clinical cases of DILI as a result of hypervitaminosis A have been described in the literature [31, 34, 36, 38–40].

N.L. Jeoffrey et al. in 2015, PNH was diagnosed due to exposure to drugs and multivitamin supplements. With unambiguous signs of portal hypertension, cirrhosis and thrombosis in the portal vein system were absent [38].

A close correlation between the severity of perisinusoidal fibrosis and the daily dose of retinol in the form of a dose-response relationship was established by M.C. Nollevaux et al. in 2006, Scientists concluded that high doses of vitamin A are toxic to the liver and can lead to cirrhosis [31].

A.P. Geubel et al. in 1991 published the results of a study of clinical symptoms and morphological characteristics of the liver of 41 patients with DILI, due to the use of vitamin A.Histological characteristics indicated hyperplasia of fat cells with fluorescent vacuoles. Liver cirrhosis was registered in 17 patients, mild chronic hepatitis – in ten, PNH – in five, “increased content of vitamin A vacuoles” – in nine patients. For 4.6 years of follow-up, six deaths were recorded due to liver disease. The exact fact of the use of vitamin A has been proven in 29 cases. Among them, the total cumulative intake was the highest in patients with liver cirrhosis (423 ± 103 × 10 ⁶ IU) and significantly lower in patients with non-cirrhotic liver disease (88.5 ± 41 IU; p

G.C. Farrell et al. in 1977 described a case of chronic hypervitaminosis A in a 57-year-old woman who took vitamin preparations for alopecia. Morphological examination of the patient’s liver showed an increase in the number and size of fat-accumulating cells under light microscopy, rapidly disappearing green autofluorescence of vitamin A. Electron microscopy confirmed the presence of fat-accumulating cells saturated with vitamin A in the Disse space and minor toxic changes in hepatocytes.The authors stated the presence of early morphological changes in the liver tissue in chronic hypervitaminosis A [34].

G. Hensley et al. in 2010 described an unusual case of intrahepatic cholestasis caused by vitamin A intoxication. The patient took Herbalife ^TM cocktail with two multivitamin tablets (daily intake of vitamin A) daily for 12 years. The impaired liver function tests corresponded to cholestatic syndrome.Liver biopsy revealed pathognomonic signs of vitamin A hepatotoxicity without the usual fibrosis. After stopping the intake of dietary supplements and multivitamins, the manifestations of cholestasis were completely stopped. This case proves that long-term use of low doses of vitamin A can cause cholestatic liver damage [37].

H.J. Kistler et al. In 1977, the reversibility of portal hypertension was observed in a patient with psoriasis who used excessive amounts of retinol for a long time.The authors presented a clinical case of manifestation of hypervitaminosis A with portal hypertension without histological signs of liver cirrhosis. All the characteristic signs of chronic intoxication were reversible after discontinuation of the drug, the impaired liver function returned to normal, and the signs of portal hypertension completely disappeared [40].

Currently, there is no reliable method for calculating the optimal dose of vitamin A. Levels of retinol in the blood do not reflect its accumulation in the liver.Therefore, vitamin A levels may remain within normal limits despite proven hepatic stellate cell hyperplasia and liver damage [31]. The most sensitive method for assessing the state of vitamin A in relation to its reserves in the liver is the isotope dilution test [41, 42].

Vitamin E hepatotoxicity

Vitamin E (alpha-tocopherol, tocotrienol) is a fat-soluble antioxidant known as an inhibitor of lipid peroxidation [24, 25].Taking into account this property, tocopherol is considered as a protector in cardiovascular diseases and is used in coronary heart disease [26]. However, animal experiments have shown that high doses of this vitamin interfere with the absorption of other fat-soluble vitamins [26]. Long-term intake of high doses of vitamin E can cause deficiencies in vitamins D, A, and K [25, 26, 43]. The daily requirement of vitamin E for men is 13 mg / day, for women – 10 mg / day. Based on the results of the conducted studies, with long-term use in doses up to 300 IU, serious side effects were rarely recorded [23, 28].Long-term use of tocopherol in excess of 800 IU / day increased the risk of bleeding, especially with vitamin K deficiency. Severe overdose leads to the development of thrombophlebitis, blockage of blood vessels [23, 28, 43]. Thus, meta-analysis data show an increase in the risk of hemorrhagic stroke by 20% with the use of vitamin E. The use of a high-dose vitamin E supplement leads to a statistically significant increase in overall mortality [33, 44]. Given these risks, experts from the American Association for the Study of Liver Disease recommend that vitamin E be used only in adults with non-alcoholic steatohepatitis, but not in diabetic patients and children [45].

In one of the major reviews of the literature on the hepatoprotective properties of vitamin E in humans and animals, it is said that vitamin E is characterized by a high hepatoprotective effect in animals, but not in humans. The hepatoprotective effect of tocopherol is associated with a decrease in oxidative stress in the liver. At the same time, microsomal lipid peroxidation, levels of tumor necrosis factor, hepatic porphyrin, liver inflammation and fibrosis decrease, levels of alanine aminotransferase and aspartate aminotransferase, alkaline phosphatase, bilirubin, glutathione improve and histopathological changes in the liver improve [22, 35].In this regard, researchers have studied the role of vitamin E in liver disease. However, analysis of the histological effect of alpha-tocopherol supplementation in non-alcoholic steatohepatitis showed no histological improvement over placebo [45]. In patients with chronic hepatitis C, high doses of alpha-tocopherol significantly reduced oxidative stress, but did not affect liver enzymes or histological features of damage [32].

In a randomized placebo-controlled study of alcoholic hepatitis, no positive effect was recorded with the use of vitamin E at a dose of 1000 IU / day [33].

Hepatotoxicity of the combined use of vitamins A and E

The literature describes isolated cases of DILI, provoked by the simultaneous intake of high doses of fat-soluble vitamins. As a rule, these are separate observations associated with hypervitaminosis A and E [35]. The most dangerous complications of hypervitaminosis A and E are myocardial infarction, sepsis, and disorders of the central nervous system. When high doses are prescribed, drowsiness, headache and nausea appear [25, 35].An excess of vitamins A and E blocks the absorption of vitamin K, possibly as a result of a competitive effect during diffusion in the proximal small intestine [26]. As a result of this enzymatic process, glutamic acid residues are converted into gamma-carboxyglutamic acid residues (Gla-radicals). Gla radicals, due to two free carboxyl groups, are involved in calcium binding and play an important role in the biological activity of all known Gla proteins [28]. Gla proteins are involved in the regulation of blood coagulation (prothrombin (factor II), factors VII, IX, X, proteins C, S and Z), bone metabolism (osteocalcin – Gla-bone protein or Gla-protein matrix) [35, 43 ].

G. Bjelakovic et al. in 2007 conducted a meta-analysis of 68 randomized trials involving 232,606 patients (385 publications) on the effect of antioxidant supplementation on all-cause mortality. It has been proven that both vitamin A (relative risk (RR) 1.16; 95% confidence interval (CI) 1.10–1.24) and vitamin E (RR 1.04; 95% CI 1.01– 1.07), individually or collectively, significantly increase mortality. Concomitant treatment with beta-carotene, vitamin A and vitamin E also increases mortality [44].

Clinical observation

Patient L., 23 years old, a housewife, was admitted to the Center for Diagnosis of Liver Diseases of the Moscow Clinical Scientific and Practical Center named after I.I. A.S. Loginova in September 2018 with complaints of heaviness in the right hypochondrium and epigastric region, general weakness, dry skin, hair loss, abdominal enlargement, edema of the lower extremities. For two years, the patient independently took the drug Aevit (a complex of fat-soluble vitamins A and E) in increased doses (15 capsules per day) for “general recovery”, which corresponded to 1,500 IU / day of alpha-tocopherol acetate and 1,500,000 IU / day of retinol …She denied the use of herbal supplements, teas, narcotic and any other drugs; she used alcohol very rarely. Family history is unremarkable. On physical examination, sclera subicterus, liver enlargement by 1.5 cm from under the edge of the costal arch, spleen by 3 cm. There are no signs of hepatic encephalopathy. Initial laboratory tests revealed a moderate increase in the levels of aspartate aminotransferase – 62.4 IU / L, alkaline phosphatase – 251 IU / L, hypoalbuminemia (albumin – 30 g / L). Hemoglobin – 114.0 g / l, erythrocytes – 3.58 × 10 ⁶ / μl, leukocytes – 3.8 × 10 ⁹ / l, platelets – 97.0 × 10 ³ / μl.Other laboratory parameters, including glucose and creatinine levels, are within normal limits. The patient started intravenous administration of ademetionine. A complete assessment of the causes of liver damage was carried out: viral hepatitis (hepatitis A, B, C and E), human immunodeficiency virus, autoimmune hepatitis (the full range of autoantibodies, the level of immunoglobulin G were investigated), systemic inflammatory diseases (systemic scleroderma, Sjogren’s syndrome) were excluded, storage diseases, in particular Wilson’s disease. The etiology of liver damage was preliminarily identified as drug-related.Ultrasound examination (US) of the abdominal cavity revealed diffuse liver changes, hepatosplenomegaly, portal hypertension, and slight ascites. According to the data of liver fibroelastometry, the elasticity was 13.3 kPA, which corresponded to the F4 stage on the METAVIR scale, that is, liver cirrhosis. A standardized assessment of the causal relationship and the severity of liver damage was performed according to the Roussel Yuklaf scale (RUCAM), according to which the etiological relationship with drugs (Aevit) was determined with a high probability (≥ 7 points).

Based on the results of laboratory and instrumental studies (cytolytic and cholestatic syndromes, hypersplenism syndrome, pronounced liver fibrosis with fibroelastometry, ultrasound signs of portal hypertension), a preliminary clinical diagnosis was established: liver cirrhosis of drug etiology, minimal biochemical activity with cholestasis syndrome, class B on the Child’s scale – Pugh (6 points), portal hypertension – enlargement of the portal and splenic veins, splenomegaly, hypersplenism syndrome – latent thrombocytopenia, mild leukopenia, hepatic encephalopathy of 0–1st degree.A liver biopsy was performed to verify the diagnosis. There were no histological signs of liver cirrhosis. When staining a biopsy specimen for copper, Wilson’s disease is excluded. When staining for iron, no changes characteristic of hemochromatosis were found. The pathological report indicated focal lobular hepatitis of drug etiology (hypervitaminosis A) (Fig. 1 and 2). Morphological conclusion: chronic focal lobular hepatitis of a low degree of activity, most likely of drug etiology (hypervitaminosis A).Activity according to METAVIR A1, fibrosis stage F1.

According to the liver biopsy, hepatitis was diagnosed due to hypervitaminosis A. Additionally, duplex scanning of the abdominal and liver vessels was performed to clarify the presence of portal hypertension. An increase in the diameter of the veins of the portal system was revealed (portal vein – 14.5 mm, splenic vein – 8.8 mm), indicating moderately pronounced signs of extrahepatic form of portal hypertension with an increase in velocity parameters along the visceral arteries.

Conclusion

Patient L., 23 years old, who had been taking the drug Aevit for a long time in high doses, developed hypervitaminosis A and E, clinically manifested by asthenic, edematous-ascitic, cytolytic and cholestatic syndromes. Based on clinical data and the result of liver fibroelastometry, hepatic cirrhosis was preliminarily diagnosed. However, the results of a morphological study did not confirm liver cirrhosis and showed a characteristic histological picture of drug-induced hepatitis.The development of PNH was most likely caused by obliteration of the Disse space as a result of hyperplasia and hypertrophy of stellate cells stimulated by lipid vacuoles accumulating retinol in their cytoplasm. The results of fibroelastometry, which showed pronounced fibrosis of the liver, can be explained by the overestimation of indicators against the background of a significant number of fatty vacuoles in the structure of the liver.

The final diagnosis was formulated as drug-induced hepatitis induced by hypervitaminosis A and E, low biochemical activity with cholestasis syndrome, A1, F1 on the METAVIR scale, PNH.

Upon discharge from the hospital, the patient was recommended to continue hepatoprotective therapy with ursodeoxycholic acid at a dose of 750 mg / day, to exclude any medications (including multivitamin supplements). After a three-month outpatient follow-up, the patient showed no progression of symptoms of the disease, she reported good health. Repeated liver function tests showed no deviations from normal values.Signs of portal hypertension were not determined, which again testified in favor of the diagnosis of PNH, which regresses when the etiological factor is eliminated.

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