Vitamin B supplementation

Although B vitamins have several vitamers, the active forms are used in Basic Micronutrition whenever possible.

The B vitamins represent a group of eight water-soluble vitamins that act as coenzymes:

Thiamine (B1). Converted to the active form, the coenzyme thiamine pyrophosphate (TPP).

Riboflavin (B2). Converted to two active forms, the coenzymes FMN and FAD. Riboflavin 5’-phosphate is the most soluble form of this vitamin.

Niacin (B3). This term encompasses nicotinic acid and niacinamide or nicotinamide, which are interconvertible. They, in turn, are converted to two active coenzymes: NAD and NADP.

Pantothenic acid (B5). Converted to two active forms: coenzyme A (CoA) and ACP. Pantethine is a vitamer of pantothenic acid that raises CoA levels more rapidly.

Vitamin B6. A family of three compounds: pyridoxal, pyridoxine, and pyridoxamine, all interconvertible. They are converted to the active enzyme pyridoxal 5′-phosphate (PLP).

Biotin (B7). Acts as coenzyme without any need for modification.

Folates (B9). Natural folates are a numerous group of compounds of foods that are metabolized to L-methylfolate, the main active form, which is also found in foods. Vitamin B12. This term encompasses the free vitamin cyanocobalamin and the active enzymes methylcobalamin and 5′-deoxyadenosylcobalamin (dibencozide).

Functions of the B vitamins

Although the vitamins in the B group are quite dissimilar chemically, their metabolic functions have classically been described as falling into one of three general categories: membrane stabilizers, hydrogen (H⁺) atom donors and electron acceptors, and vitamin coenzymes. Their functions in human health are much broader than described here and often include participation in proper gene expression.

Intake and deficiencies

Vitamin B deficiency is common in the elderly.

Intake. The B vitamin concentration depends on external inputs, although some, such as niacin, can be synthesized from the amino acid tryptophan. Average intake of B vitamins is similar to or lower than the NRV, and therefore people with decreased absorption or increased needs can easily develop a deficiency. Around 10% of the population consumes less than half the NRV of most vitamins in the B group.

Deficiency in one of the B vitamins is often associated with deficiency in others, and these deficiencies are generally common in the elderly (García-Arias et al., 2003).

The yeast used in beer brewing makes this beverage a source of vitamins in the B group (Winkler, Wirleitner et al. 2006). However, its bioavailability ranges from poor to negative when it is taken into account that ethanol consumption inhibits absorption of several vitamins in the group (Hoyumpa 1980; Leevy 1982; Pinto, Huang et al. 1987; Spivak and Jackson 1977; Said, Sharifian et al. 1990). In general, consumption of ethanol-based beverages leads to a deficiency of these B vitamins and the health risks associated with these deficiencies.

The B vitamins are water soluble, eliminated rapidly, and not stored in the body (except for vitamin B12), so they must be replenished daily.

Because foods are a source of the different vitamins in the B complex, it is not surprising that diets deficient in one B vitamin are very likely to also be deficient, in different proportions, of others. Cooking and preparation methods also affect the micronutritional content of foods. Water-soluble vitamins are quickly destroyed during cooking in water and by heat (although niacin is thermostable). Milling and removal of the germ from cereal grains eliminates nearly all thiamine, riboflavin, and niacin. Therefore, it is very important to supplement the vitamins in the B group and other micronutrients as a balanced complex, never in isolation or in high doses.

Thiamine (B1)

Thiamine (B1) deficiency is common in chronic diseases like diabetes and heart disease.

Thiamine is found in small amounts in foods and is easily destroyed in industrial and culinary processes: heat, oxidation, additives, certain enzymes.

Diet. An excess of carbohydrates or refined products increases thiamine needs. Additionally, a diet rich in foods with high thiaminase levels (fresh fish or shellfish, for example) and/or foods high in anti-thiamine factors (tea or coffee, for example) also increase these needs (Highdon 2002).

Drugs. The anti-cancer drug 5-fluorouracil inhibits conversion of thiamine to TPP (Schumann 1999). The use of diuretics, particularly furosemide, can increase the risk of thiamine deficiencies in individuals with marginal intake, due to increased urinary excretion of the vitamin (Rieck, Halkin et al. 1999).

Riboflavin (B2)

Riboflavin deficiency (ariboflavinosis) tends to be accompanied by other nutritional deficiencies and can lead to vitamin B6 and niacin deficiency. It is known that diseases like cancer, heart disturbances, and diabetes mellitus precipitate or exacerbate riboflavin deficiency.

This deficiency is always accompanied by that of the other vitamins (Brody 1999), particularly ones in the B group.

In a study with omnivores, vegetarians, and vegans, riboflavin deficiency was found in 10% of the omnivores and vegetarians and 30% of the vegans (Majchrzak et al., 2006).

There is no evidence of adverse effects due to excessive riboflavin intake, possibly because it is absorbed in limited form in the intestine and excreted rapidly in urine.

Drugs. Antipsychotics like chlorpromazine and tricyclic antidepressants inhibit the conversion of riboflavin to FAD or FMN, as in the case of antimalarials such as quinacrine and chemotherapeutic agents such as adriamycin.

Niacin (B3)

It is not essential: the vitamin can be ingested in food or synthesized from tryptophan. As a result, deficiencies are rare in industrialized countries, although they are seen under conditions of malnutrition or chronic alcohol abuse (Pitsavas, Andreou et al. 2004).

Drugs. Long-term treatment with 5-fluorouracil has been reported to cause symptoms of pellagra, which can require niacin supplements, something that is also true of treatments with the tuberculosis drug isoniazide (Highdon 2002). Estrogens increase the efficiency of niacin synthesis from tryptophan, which reduces niacin nutritional requirements (Highdon 2002).

Pantothenic acid (B5)

Deficiency is very rare and has only been observed in severe cases of malnutrition, as seen in some wars (Plesofsky-Vig 1999).

Drugs. Oral contraceptives and similar drugs can increase requirements (Flodin 1988).

Vitamin B6

Vitamin B6 deficiency is common in the population.

Low intake. A third of adults may not be obtaining the recommended amounts of vitamin B6, and some authors believe that 80% of the population may not be receiving all the B6 the body needs.

Deficiency. According to the American Journal of Clinical Nutrition Volume 87, pages 1446-54: “Trends of Vitamin B6 Status in US Population Sample.” (Morris MS, Picciano, MF, Jacques PF, Selhub, J.), a quarter of the population may have B6 levels below 20 nmol/L, the point at which symptoms appear, but the optimal levels for cell functioning are higher than this figure. People over the age of 65 represent an especially vulnerable sector.

In a study with omnivores, vegetarians, and vegans, a third were deficient in B6, regardless of diet (Majchrzak et al., 2006).

Difficulties in obtaining from sources: in the case of grains, it is not absorbable, and in the case of animal products, it is easily lost in cooking.

Proteins. Vitamin B6 needs depend on the amount of protein consumed, the greater the amount, the greater the need for B6.

Alcohol. As in the case of other B vitamins, alcohol abusers are considered to be at risk of vitamin B6 deficiency due to low dietary intake and altered metabolism of the vitamin.

Drugs. Some drugs interfere in vitamin B6 metabolism, making some individuals more susceptible to deficiencies. The following can accentuate a marginal deficiency: oral contraceptives, hormone replacement therapy, furosemide, and bronchodilators.

Biotin (B7)

Deficiency is very rare, although it has been observed in two situations: prolonged parenteral nutrition without biotin supplementation, and consumption of fresh raw eggs. In the latter case, cooking and the resulting denaturation of the avidin in eggs, which is related to the problem, would avoid this problem (Holmberg, Blomstergren et al. 2005). High doses of vitamin B5 can also have an effect, as it competes for the same intestinal transporter (Debourdeau, Djezzar et al. 2001).

Folates (B9)

Folate deficiency is common in the population.

Intake. The NHANES III and CSFII surveys conducted in the 1990s indicated that most adults were not consuming adequate amounts of folate (Alaimo, McDowell et al. 1994; Raiten and Fisher 1995). The folate enrichment program carried out in the United States after this time increased the synthetic folic acid content of common foods like cereals and grains. This has allowed the majority of adult Americans to have a diet that meets the recommended doses of the folate equivalents (Lewis, Crane et al. 1999).

Deficiency. Serum folate levels of 3 μg/L or lower indicate deficiency (Johnson 2007). Cobalamin deficiencies can lead to folate deficiencies, which raise homocysteine levels and ultimately can lead to the development of heart disease or congenital defects (Varela-Moreiras, Murphy et al. 2009). According to the ENIDE survey in Spain, 76% to 94% of the population has a risk of inadequate intake. These results seem worrisome, particularly in the case of women in their childbearing years, due to the risk of fetal nervous system malformations (AECOSAN, 2011).

Increased requirements. Alcohol abuse, pregnancy, and cancer increase requirements and can lead to a collateral deficiency (Herbert, 1999).

Drugs. There are also cases of drugs, such as NSAIDs consumed in high doses or the use of anticonvulsants, which inhibit intestinal absorption of folates (Apeland, Mansoor et al. 2001). Treatments for dyslipidemia, such as cholestyramine, also reduce intestinal absorption (Anonymous 2001). The use of methotrexate, trimethoprim, pyrimethamine, triamterene, sulfasalazine, and hormonal contraceptives leads to folate deficiency symptoms that can be remedied through supplementation (Highdon, 2002). In addition, the following can accentuate a marginal deficiency: sulfasalazine, NSAIDs, antacids, cimetidine, ranitidine, omeprazole, metformin, furosemide, and thiazides.

Folic acid and L-methylfolate. Folate absorption varies greatly from one person to the next and, moreover, a high percentage of the population (40%–60%) have genetic polymorphisms (MTHFR polymorphisms) that prevent its conversion to L-methylfolate (L-methyltetrahydrofolate), the active form that reduces homocysteine. These individuals may need more folates from foods or L-methylfolate, but not high doses of folic acid, as this would not be active and could accumulate, having negative health consequences (Bailey and Gregory 1999; Kauwell, Wilsky et al. 2000).

Vitamin B12

12 deficiency is common in the population, mainly among the elderly.

Deficiency. Deficiencies affect 10% to 15% of people over the age of 60 (Baik and Russell 1999). Vitamin B12 is exclusively supplied by foods of animal origin: meats, fish, shellfish, eggs, and milk. Industrial and culinary processes eliminate 30% to 70% of the initial B12 content. B12 absorption requires acidity and certain enzymes to release it from its bond with food proteins, as well as the intrinsic (Castle’s) factor for the vitamin to bind to it for absorption in the intestine. Stomach acid releases the vitamin from foods and facilitates its binding to the R proteins. In the small intestine, the alkaline pH and pancreatic enzymes release it from the R protein, associating it with what is known as the intrinsic factor. Complexes of this factor with the vitamin can only be absorbed in the presence of calcium (Herbert 1996).

Drugs. The drugs used to treat gastric secretion problems, such as proton pump inhibitors (omeprazole or lansoprazole) and H2 antihistimines (ranitidine or famotidine), prevent the release and absorption of vitamins from foods, although to a lesser degree than from supplements. However, problems do not tend to appear until approximately two to three years after starting treatment (Kasper 1999)(Termanini, Gibril et al. 1998).

Other problematic drugs include cholestyramine, chloramphenicol, neomycin, and colchicine. Some anti-diabetic drugs, such as metformin, interfere with the calcium required for intestinal absorption and may, therefore, affect it. This can, however, be corrected with calcium supplements or by increasing intake of dairy products (Herbert 1996).

High doses of folic acid on a continuous basis reduce B12 blood levels. This can occur with pregnant women treated with folic acid. The total serum level of B12 is a late indicator of B12 deficiency.

Common medications that can reduce B12 levels over the long term include the following: folic acid supplements, hormonal contraceptives, antacids, omeprazole, ranitidine, metformin, allopurinol, and colchicine.

Vegetarians. It should be noted that vitamin B12 is not available from plant sources, which means that deficiency of this vitamin can be a serious problem for vegans. Nonetheless, some producers of processed plant-based foods report the vitamin B12 content. This confusion is due to a faulty interpretation of the standard method of the US Pharmacopoeia (USP) for determining vitamin B12 content. Similarly, there can be cases of over-reporting of the content of this vitamin in other types of foods (Herbert 1988).

Old age. The following are common in old age and increase the incidence of B12 deficiency: hypochlorhydria, reduced intrinsic factor levels, a diet with less meat and fish, use of proton pump inhibitors (omeprazole), etc. They also induce deficiency of folic acid.

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Reference values

NRV, PRI, UL for the B vitamins

Although most of the B vitamins are eliminated regularly in urine, consumption of high doses of certain B vitamins can produce harmful effects:

Thiamine (B1)

The NRV is 1.1 mg. The PRI is 1 mg for women and 1.2 mg for men.

It produces no harmful effects at high doses. Excretion is directly proportional to intake, and it does not accumulate in tissues. Nonetheless, it is not advisable to exceed 100 mg in long-term administration. No maximum tolerated intake levels have been reported (Anonymousb3 1998), and cases of toxicity due to oral intake are unknown. Even so, some cases of anaphylaxis caused by high doses of thiamine administered intravenously or intramuscularly have been described. However, the doses were higher than those that humans are able to absorb from oral intake (Anonymousb3 1998).

There is no UL defined at the moment.

Riboflavin (B2)

The NRV is 1.4 mg. The PRI is 1.1 mg for women and 1.8 for men.

It produces no harmful effects at high doses. Excretion is directly proportional to intake, and it does not accumulate in tissues. Nonetheless, it is not advisable to exceed 200 mg in long-term administration.

There is no UL defined at the moment.

Niacin (B3)

The NRV is 16 mg. The PRI is 15 mg for women and 20 mg for men.

The UL for nicotinamide is 900 mg.

Megadoses (1.5–4 g) of nicotinic acid can improve the lipid profile, but they cause side effects: flushing, itching, nausea, and liver damage.

There have been reports of maximum tolerated intakes of 35 mg/day from supplements, drugs, or enriched foods (Anonymousb3 1998) which have given rise to cases of flushing (reddening of the skin, frequently accompanied by itching and a slight burning sensation). Intake of 3,000 mg/day of nicotinamide and 1,500 mg/day of nicotinic acid are associated with nausea, vomiting, and signs and symptoms of liver toxicity (Anonymousb3 1998).

Pantothenic acid (B5)

La VRN es de 6 mg. The PRI for adults, both men and women, is 5 mg.

It produces no harmful effects at high doses. Excretion is directly proportional to intake, and it does not accumulate in tissues. Nonetheless, it is not advisable to exceed 1,000 mg in long-term administration.

There is no UL defined at the moment.

Vitamin B6

The NRV is 1.4 mg. The PRI is 1.3–1.5 mg for women and 1.3–1.8 mg for men.

The UL is 25 mg.

Maximum tolerated intakes of 100 mg/day from supplements, drugs, or enriched foods (Anonymousb6 1998) which can give rise to cases of flushing (reddening of the skin, frequently accompanied by itching and a slight burning sensation) were reported.

Biotin (B7)

The NRV is 50 µg. The PRI is 30 mg for adult men and women.

It produces no harmful effects at high doses. Excretion is directly proportional to intake, and it does not accumulate in tissues. Nonetheless, it is not advisable to exceed 2,500 mg in long-term administration.

There is no UL defined at the moment.

Folic acid (B9)

The NRV for adults is 200 µg. The PRI for adults is 400 µg.

The UL is 1,000 µg.

It is not toxic. The maximum known tolerated intake is 1 mg/day (Anonymousb9 1998), beyond which the signs and symptoms of vitamin B12 deficiency are masked, leading to permanent neurological damage (Anonymousb9 1998).

Doses of up to 15 mg/day of folic acid have been administered, but its safety in individuals who do not metabolize folic acid properly due to genetic polymorphisms affecting folic acid metabolism is currently being questioned.

Vitamin B12

The NRV is 2.5 µg. The PRI is 2.4 µg for women and men.

While not toxic, it is stored in the liver and exceeding 3,000 µg in long-term administration is not advisable.

There is no UL defined at the moment.

NRV: Nutrient Reference Value. These are the daily amounts recommended for vitamins and minerals (micronutrients only) considered sufficient in the European Union to prevent a deficit in most healthy individuals in the population. They are the values used for labeling and claims.

PRI: Population Reference Intake. These are the reference values for a specific population group, defined as the amount of energy and/or nutrients (macronutrients and micronutrients) recommended to cover the nutritional needs of practically the entire population. They refer to healthy population groups. The values are expressed per person per day, as a 15-day average. To account for individual differences in digestive and metabolic processes, the PRI figure used for each nutrient is the average plus twice the standard deviation (except for energy, for which the average is used), thereby including almost all healthy individuals in the group (97.5%).

UL: Tolerable Upper Intake Level: the maximum level of total daily intake of a nutrient in a context of long-term or chronic consumption which does not pose a risk to health.

Foods with B vitamins

The B vitamins are found all whole and unprocessed foods. Processing, or the use of sugars or flour, reduces the B vitamin content of foods. These vitamins are especially abundant in meats (particularly turkey and tuna) and derived products such as liver. Other good sources are potatoes, bananas, lentils, chili peppers, peas, molasses, etc.

The B vitamin content of foods can be reduced by 20% to 90% due to a variety of factors: storage, processing, freezing, canning, refining of grains, contact with air and light, and cooking and exposure to heat.

Vitamins A, E, C and B, and carotenoids are quite unstable and affected to a greater or lesser degree by these factors. Storage and cooking produce a significant loss of folates and vitamin C. Culinary processes result in a 50% reduction in folate content; in fried foods, this is 90%, and in boiled vegetables it is 70%.

NADH or nicotinamide adenine dinucleotide phosphate. This is an active form of niacin. It is found in meats, poultry, and fish, but it is not known whether its content in foods can be absorbed and utilized by the body.

Folates. Green leafy vegetables are a good source of folates. Asparagus, watercress, chives, endive, spinach, leeks, escarole, liver, foie-gras, paté, and eggs contain folates in significant amounts. Storage and cooking produce a significant loss of folates. Culinary processes result in a 50% reduction in folate content; in fried foods, this is 90%, and in boiled vegetables it is 70%.

Vitamin B12. Vitamin B12 is contained in foods of animal origin: liver and other organ meats, foie-gras, paté, rabbit, beef, lamb, poultry, fish, shellfish, and aged cheeses. Plants do not contain bioavailable vitamin B12 with biological activity. Vitamin B12 is more stable than the others, although exposure to intense and prolonged heat also destroys it.

Many foods contain B vitamins. The main sources are the following:

• Nuts and seeds: walnuts, almonds, hazelnuts, peanuts, pine nuts, pistachios, and sunflower seeds.
• Legumes: soybeans, lentils, chick peas, peas, etc.
• Whole eggs.
• Liver.
• Oily fish.
• Whole grains: wheat, oats, rye, rice, etc.

Folates:

• Green leafy vegetables, asparagus, watercress, chives, endive, spinach, leeks, and escarole.
• Livers, foie-gras, and paté.
• Whole eggs.

Vitamin B12:

• Liver and other organ meats, foie-gras, paté, etc.
• Rabbit, beef, lamb, poultry, etc.
• Fish and shellfish.
• Aged cheeses.

Vegetables, while they do contain molecules with a similar chemical structure to vitamin B12 (corrinoids), these are not bioavailable forms with biological activity.

Information for professionals