Important Of Skin Molecules

Important Skin Molecules

Health, resilience and youthful appearance of the skin depends, among other things, on several key classes of biological molecules, just like the quality of a house depends on the quality of bricks, beams and concrete. The most important skin molecules are collagen, elastin, glycosoaminoglycans and proteoglycans.

Collagen is a protein forming the structural grid that holds other skin structures. It plays a role somewhat similar to that of steel rods in a reinforced concrete block. It gives the skin its strength and durability. As any other protein, collagen is composed of amino acids. However, it is unusually rich in a few specific amino acids, proline, hydroxyproline, lysine and glycine. Some experts believe that foods or supplements rich in these amino acids may benefit the skin by stimulating collagen production. There is a number of other ways to stimulate collagen production, including topical vitamin C and copper peptides. Increasing collagen production is important because age-related decline in the collagen synthesis is partly responsible for the signs of skin aging such as thinning, wrinkles and sagging.

Elastin is also a protein. It is more stretchable than collagen and helps maintain skin resilience and elasticity. Elastin contains two special amino acids, desmosine and isodesmonsine. When both elastin and collagen and abundant and undamaged, the skin easily regains its shape after being stretched or folded. Just as collagen, elastin deteriorates with age, leading to wrinkles and facial sag.

Glycosoaminoglycans (GAGs) and proteoglycans are special biological polymers whose key role is to hold moisture in the skin. In essense, they are extremely effective natural moisturizers - far more effective that common cosmetic moisturizers. Hydrated GAGs and proteoglycans help the skin stay plump and fresh and provide mechanical support for skin cells. GAGs are composed of special units (mainly water-holding sugars) such as glucosamine hydrochloride, N-acetyl glucosamine, and glucosamine sulfate. These units combine to form various types of GAGs, such as hyaluronic acid, keratin sulfate, heparin, heparin sulfate, dermatin sulfate, and chondroitin sulfate. Proteoglycans are larger than GAGs and are formed when certain types of GAGs are attached to a protein backbone. Since GAGs and proteoglycans are composed largely of water-holding sugars, supplementing one's diet with these sugars may enhance the skins production of GAGs and proteoglycans. In particular, N-acetyl-D-glucosamine, D-glucosamine hydrochloride, and D-glucosamine sulfate are often used as supplemets to increase skin moisture.

Vitamin B 12

Vitamin B 12 is the largest and most complex of all the vitamins . It is unique among vitamins in that it contains a metal ion , cobalt. For this reason cobalamin is the term used to refer to compounds having B 12 activity. Methylcobalamin and 5-deoxyadenosyl cobalamin are the forms of vitamin B 12 used in the human body (1) . The form of cobalamin used in most supplements , cyanocobalamin, is readily converted to 5-deoxyadenosyl and methylcobalamin.
Vitamin B 12: function
Cofactor for methionine synthase

Methylcobalamin is required for the function of the folate-dependent enzyme , methionine synthase. This enzyme is required for the synthesis of the amino acid , methionine , from homocysteine . Methionine is required for the synthesis of S-adenosylmethionine, a methyl group donor used in many biological methylation reactions, including the methylation of a number of sites within DNA and RNA (2) . Methylation of DNA may be important in cancer prevention. Inadequate function of methionine synthase can lead to an accumulation of homocysteine, which has been associated with increased risk of cardiovascular diseases ( diagram ).
Cofactor for L-methylmalonyl-CoA mutase

5-Deoxyadenosylcobalamin is required by the enzyme that catalyzes the conversion of L-methylmalonyl-CoA to succinyl-CoA. This biochemical reaction plays an important role in the production of energy from fats and proteins. Succinyl CoA is also required for the synthesis of hemoglobin , the oxygen carrying pigment in red blood cells (2) .
Vitamin B 12: deficiency

Vitamin B 12 deficiency is estimated to affect 10%-15% of individuals over the age of 60 (3. Absorption of vitamin B 12 from food requires normal function of the stomach, pancreas , and small intestine . Stomach acid and enzymes free vitamin B 12 from food , allowing it to bind to other proteins , known as R proteins (2) . In the alkaline environment of the small intestine, R proteins are degraded by pancreatic enzymes, freeing vitamin B 12 to bind to intrinsic factor (IF), a protein secreted by specialized cells in the stomach. Receptors on the surface of the small intestine take up the IF-B 12 complex only in the presence of calcium , which is also supplied by the pancreas (4) . Vitamin B 12 can also be absorbed by passive diffusion, but this process is very inefficient, allowing only about 1% absorption of a vitamin B 12 dose.
Causes of vitamin B 12 deficiency

The most common causes of vitamin B 12 deficiency are 1) an autoimmune condition known as pernicious anemia and 2) food-bound vitamin B 12 malabsorption. Although both causes become more common with age, they are two separate conditions (3) .
Vitamin B 12: pernicious anemia

Pernicious anemia has been estimated to be present in approximately 2 % of individuals over 60 (5) . Although anemia is often a symptom, the condition is actually the end stage of an autoimmune inflammation of the stomach, resulting in destruction of stomach cells by one's own antibodies . Progressive destruction of the cells that line the stomach cause decreased secretion of acid and enzymes required to release food bound vitamin B 12 . Antibodies to intrinsic factor (IF) bind to IF preventing formation of the IF-B 12 complex , further inhibiting vitamin B 12 absorption. If the body's vitamin B 12 stores are adequate prior to the onset of pernicious anemia , it may take years for symptoms of deficiency to develop. About 20% of the relatives of pernicious anemia patients also have pernicious anemia , suggesting a genetic predisposition . Treatment of pernicious anemia generally requires injections of vitamin B 12 , bypassing intestinal absorption. High-dose oral supplementation is another treatment option, because consuming 1,000 mcg (1 mg)/day of vitamin B 12 orally should result in the absorption of about 10 mcg/day (about 1%) by passive diffusion (3).
Food-bound vitamin B 12 malabsorption

Food-bound vitamin B 12 malabsorption is defined as an impaired ability to absorb food or protein-bound vitamin B 12 , although the free form is fully absorbable (6) . In the elderly, food-bound vitamin B 12 malabsorption is thought to result mainly from atrophic gastritis, a chronic inflammation of the lining of the stomach, which ultimately results in the loss of glands in the stomach (atrophy) and decreased stomach acid production. Because stomach acid is required for the release of vitamin B 12 from the proteins in food, vitamin B 12 absorption is diminished. Decreased stomach acid production also provides an environment more conducive to the overgrowth of anaerobic bacteria in the stomach, interfering further with vitamin B 12 absorption (2) . Because vitamin B 12 in supplements is not bound to protein , and because intrinsic factor (IF) is still available, the absorption of supplemental vitamin B 12 is not reduced as it is in pernicious anemia . Thus, individuals with food-bound vitamin B 12 malabsorption do not have an increased requirement for vitamin B 12 ; they simply need it in the form of a supplement rather than from food .
Atrophic gastritis

Atrophic gastritis is thought to affect 10% - 30% of people over 60 years of age, and is frequently associated with infection by the bacteria, Heliobacter pylori. H. pylori infection induces a chronic inflammation of the stomach which may progress to peptic ulcer disease , atrophic gastritis, and/or gastric cancer in some individuals. The relationship of H. pylori infection to atrophic gastritis, gastric cancer, and vitamin B 12 deficiency is presently an area of active research (3) .
Other causes of vitamin B 12 deficiency

Other causes of deficiency include surgical resection of the stomach or portions of the small intestine where receptors for the IF- B 12 complex are located. Conditions affecting the small intestine, such as malabsorption syndromes (celiac disease and tropical sprue), may also result in vitamin B 12 deficiency . Because the pancreas provides critical enzymes as well as calcium required for vitamin B 12 absorption , pancreatic insufficiency may contribute to vitamin B 12 deficiency . Since vitamin B 12 is found only in foods of animal origin, a strict vegetarian (vegan) diet has resulted in cases of vitamin B 12 deficiency . In alcoholics, vitamin B 12 intake and absorption are reduced, while elimination is increased (5) . Individuals with acquired immunodeficiency syndrome (AIDS) appear to be at increased risk of deficiency, possibly related to a failure of the IF-B 12 receptor to take up the IF-B 12 complex (2) . Long-term use of acid-reducing drugs has also been implicated in vitamin B 12 deficiency .
Symptoms of vitamin B 12 deficiency

Vitamin B 12 deficiency results in impairment of the activities of B 12 -requiring enzymes. Impaired activity of methionine synthase may result in elevated homocysteine levels, while impaired activity of L-methylmalonyl-CoA mutase results in increased levels of a metabolite of methylmalonyl-CoA, called methylmalonic acid (MMA). Individuals with mild vitamin B 12 deficiency may not experience symptoms, although blood levels of homocysteine and/or MMA may be elevated (7) .
Megaloblastic anemia

Diminished activity of methionine synthase in vitamin B 12 deficiency inhibits the regeneration of tetrahydrofolate (THF) and traps folate in a form that is not usable by the body ( diagram ), resulting in symptoms of folate deficiency even in the presence of adequate folate levels. Thus, in both folate and vitamin B 12 deficiency , folate is unavailable to participate in DNA synthesis. This impairment of DNA synthesis affects the rapidly dividing cells of the bone marrow earlier than other cells, resulting in the production of large, immature, hemoglobin-poor red blood cells. The resulting anemia is known as megaloblastic anemia and is the symptom for which the disease, pernicious anemia, was named (2) . Supplementation of folic acid will provide enough usable folate to restore normal red blood cell formation . However, if vitamin B 12 deficiency was the cause, it will persist despite the resolution of the anemia. Thus, megaloblastic anemia should not be treated with folic acid until the underlying cause has been determined (4) .
Neurologic symptoms

The neurologic symptoms of vitamin B 12 deficiency include numbness and tingling of the arms and more commonly the legs, difficulty walking, memory loss, disorientation, and dementia , with or without mood changes. Although the progression of neurologic complications is generally gradual, they are not always reversible with treatment of vitamin B 12 deficiency , especially if they have been present for a long time. Neurologic complications are not always associated with megaloblastic anemia , and are the only clinical symptom of vitamin B 12 deficiency in about 25% of cases (5) . Although vitamin B 12 deficiency is known to damage the myelin sheath covering cranial, spinal, and peripheral nerves, the biochemical processes leading to neurological damage in vitamin B 12 deficiency are not well understood (2) .
Gastrointestinal symptoms

A sore tongue, appetite loss, and constipation have also been associated with vitamin B 12 deficiency . Their origins are unclear, but may be related to the stomach inflammation underlying some cases of vitamin B 12 deficiency , or the increased vulnerability of the rapidly dividing cells along the gastrointestinal tract to impaired DNA synthesis (5) .
Vitamin B 12: the Recommended Dietary Allowance (RDA)

The current RDA was revised by the Food and Nutrition Board (FNB) of the Institute of Medicine in 1998. Because of the increased risk of f ood-bound vitamin B 12 malabsorption in older adults, the FNB recommended that adults over 50 years of age get most of the RDA from fortified food or vitamin B 12 -containing supplements (5) .

Recommended Dietary Allowance (RDA) for Vitamin B 12
Life Stage Age Males (mcg/day) Females (mcg/day)
Infants 0-6 months 0.4 (AI) 0.4 (AI)
Infants 7-12 months 0.5 (AI) 0.5 (AI)
Children 1-3 years 0.9 0.9
Children 4-8 years 1.2 1.2
Children 9-13 years 1.8 1.8
Adolescents 14-18 years 2.4 2.4
Adults 19-50 years 2.4 2.4
Adults 51 years and older 2.4* 2.4*
Pregnancy all ages - 2.6
Breastfeeding all ages - 2.8

* Vitamin B 12 intake should be from supplements or fortified foods , due to the age-related increase in food bound malabsorption.
Disease Prevention
Homocysteine and cardiovascular disease

Evidence is mounting that an elevated plasma homocysteine concentration is an independent risk factor for cardiovascular diseases , including heart disease, stroke, and peripheral vascular disease . The amount of homocysteine in the blood is regulated by at least three vitamins : folate, vitamin B 12 , and vitamin B 6 ( diagram ). Analysis of the results of 12 homocysteine-lowering trials showed folic acid supplementation (0.5-5 mg/day) to have the greatest lowering effect on blood homocysteine levels (25%), with vitamin B 12 (0.5 mg/day or 500 mcg/day) providing an additional 7% reduction (8) . The results of a sequential supplementation trial in 53 men and women indicated that after folic acid supplementation , vitamin B 12 became the major determinant of plasma homocysteine (9) . Some evidence indicates that vitamin B 12 deficiency is a major cause of elevated homocysteine levels in people over the age of 60. Two studies found blood methylmalonic acid (MMA) levels to be elevated in more than 60 % of elderly individuals with elevated homocysteine levels. An elevated MMA level in conjuction with elevated homocysteine suggests either a vitamin B 12 deficiency, or a combined vitamin B 12 and folate deficiency, in the absence of impaired kidney function (10) . Thus, it is important to evaluate vitamin B 12 status as well as kidney function in older individuals with elevated homocysteine levels, prior to initiating homocysteine-lowering therapy. For more information regarding homocysteine and cardiovascular diseases, see folic acid .
Cancer

Folate is required for synthesis of DNA , and there is evidence that decreased availability of folate results in strands of DNA that are more susceptible to damage. Deficiency of vitamin B 12 traps folate in a form that is unusable by the body for DNA synthesis. Both vitamin B 12 and folate deficiencies result in a diminished capacity for methylation reactions ( diagram ). Thus, vitamin B 12 deficiency may lead to an elevated rate of DNA damage and altered methylation of DNA, both of which are important risk factors for cancer . A recent series of studies in young adults and older men indicated that increased levels of homocysteine and decreased levels of vitamin B 12 in the blood were associated with a biomarker of chromosome breakage in white blood cells. In a double blind , placebo -controlled study the same biomarker of choromosome breakage was minimized in young adults who were supplemented with 700 mcg of folic acid and 7 mcg of vitamin B 12 daily in cereal for two months (11) .
Breast cancer

A case-control study compared prediagnostic levels of serum folate, vitamin B6 , and vitamin B 12 in 195 women later diagnosed with breast cancer and 195 age-matched women who were not diagnosed with breast cancer (12) . Among women who were postmenopausal at the time of blood donation, the association between blood levels of vitamin B 12 and breast cancer suggested a threshold effect. The risk of breast cancer was more than doubled in those women with serum vitamin B 12 levels in the lowest quintile (1/5) compared to those women in the four highest quintiles. The investigators found no relationship between breast cancer and serum levels of vitamin B 6 , folate, or homocysteine. Because this study was obsrvational , it cannot be determined whether decreased serum levels of vitamin B 12 were a cause or a result of breast cancer . Previously, there has been little evidence to suggest a relationship between vitamin B 12 status and breast cancer risk. However, the above studies point to a need for further investigation of the relationship between vitamin B 12 status and cancer risk.
Neural tube defects

Neural tube defects (NTD) may result in anencephaly or spina bifida , devastating and sometimes fatal birth defects. The defects occur between the 21st and 27th days after conception, a time when many women do not realize they are pregnant (13) . Randomized controlled trials have demonstrated 60% to 100% reductions in NTD cases when women consumed folic acid supplements in addition to a varied diet during the month before and the month after conception. Increasing evidence indicates that the homocysteine -lowering effect of folic acid plays a critical role in lowering the risk of NTD (14) . Homocysteine may accumulate in the blood when there is inadequate folate and/or vitamin B 12 for effective functioning of the methionine synthase enzyme . Decreased vitamin B 12 levels in the blood and amniotic fluid of pregnant women have been associated with an increased risk of NTD, suggesting that adequate vitamin B 12 intake in addition to folic acid may be beneficial in the prevention of NTD.
Alzheimer's disease and dementia

Individuals with Alzheimer's disease often have low blood levels of vitamin B 12 . One study found lower vitamin B 12 levels in the cerebrospinal fluid of patients with Alzheimer's disease than in patients with other types of dementia , though blood levels of vitamin B 12 did not differ (15) . The reason for the association of low vitamin B 12 status with Alzheimer's disease is not clear. Vitamin B 12 deficiency , like folate deficiency, may lead to decreased synthesis of methionine and S-adenosylmethionine, adversely affecting methylation reactions essential for the metabolism of components of the myelin sheath of nerve cells, as well as neurotransmitters . Moderately increased homocysteine levels, as well as decreased folate and vitamin B 12 levels have also been associated with Alzheimer's disease and vascular dementia . A case-control study of 164 patients with dementia of Alzheimer's type included 76 cases in which the diagnosis of Alzheimer's disease was confirmed by examination of the brain cells after death (16) . Compared to 108 control subjects without evidence of dementia, subjects with dementia of Alzheimer's type and confirmed Alzheimer's disease had higher blood homocysteine levels and lower folate and vitamin B 12 levels. Measures of general nutritional status indicated that the association of increased homocysteine levels and diminished vitamin B 12 status with Alzheimer's disease was not due to dementia-related malnutrition. Low serum vitamin B 12 (< 150 pmol/L) or folate (< 10 nmol/L) levels were associated with a doubling of the risk of developing Alzheimer's disease in 370 elderly men and women followed over 3 years (17) . In a sample of 1092 men and women without dementia followed for an average of 10 years, those with higher plasma homocysteine levels at baseline had a significantly higher risk of developing Alzheimer's disease and other types of dementia (18) . Those with plasma homocysteine levels greater than 14 mmol/L had nearly double the risk of developing Alzheimer's disease.
Depression

Observational studies have found as many as 30% of patients hospitalized for depression to be deficient in vitamin B 12 (19) . A recent cross-sectional study of 700 community-living, physically disabled women over the age of 65 found that vitamin B 12 deficient women were twice as likely to be severely depressed as non- deficient women (20) . The reasons for the relationship between vitamin B 12 deficiency and depression are not clear. Vitamin B 12 and folate are required for the synthesis of S-adenosylmethionine, a methyl group donor essential for the metabolism of neurotransmitters , whose bioavailability has been related to depression . Because few studies have examined the relationship of vitamin B 12 status and the development of depression over time, it cannot yet be determined if vitamin B 12 deficiency plays a causal role in depression . However, due to the high prevalence of vitamin B 12 deficiency in older individuals, it may be beneficial to screen them for vitamin B 12 deficiency as part of a medical evaluation for depression .
Vitamin B 12: sources
Food sources

Only bacteria can synthesize vitamin B 12 . Vitamin B 12 is present in animal products such as meat, poultry, fish (including shellfish), and to a lesser extent milk, but it is not generally present in plant products or yeast (1) . Fresh pasteurized milk contains 0.9 mcg per cup and is an important source of vitamin B 12 for some vegetarians (5) . Those vegetarians who eat no animal products need supplemental vitamin B 12 to meet their requirements. Also, individuals over the age of 50 should obtain their vitamin B 12 in supplements or fortified foods like fortified cereal because of the increased likelihood of food-bound vitamin B 12 malabsorption.

Most people do not have a problem obtaining the RDA of 2.4 mcg/day of vitamin B 12 in food . In the United States, the average intake of vitamin B 12 is about 4.5 mcg/day for young adult men, and 3 mcg/day for young adult women. In a sample of adults over the age of 60, men were found to have an average dietary intake of 3.4 mcg/day and women 2.6 mcg/day (5) . Some foods with substantial amounts of vitamin B 12 are listed in the table below along with their vitamin B 12 content in micrograms (mcg). For more information on the nutrient content of foods you eat frequently, search the USDA food composition database.
Food Serving Vitamin B 12 (mcg)
Clams (steamed) 3 ounces 84.0
Mussels (steamed) 3 ounces 20.4
Crab (steamed) 3 ounces 8.8
Salmon (baked) 3 ounces* 2.4
Rockfish (baked) 3 ounces 1.0
Beef (cooked) 3 ounces 2.1
Chicken (roasted) 3 ounces 0.3
Turkey (roasted) 3 ounces 0.3
Egg (poached) 1 large 0.4
Milk 8 ounces 0.9
Brie (cheese) 1 ounce 0.5

*A three-ounce serving of meat or fish is about the size of a deck of cards.
Vitamin B 12: supplements

Cyanocobalamin is the principal form of vitamin B 12 used in supplements but methylcobalamin is also available. Cyanocobalalmin is available by prescription in an injectable form and as a nasal gel for the treatment of pernicious anemia . Over the counter preparations containing cyanocobalamin include multivitamin , vitamin B-complex , and vitamin B 12 supplements (21) .
Safety
Toxicity

No toxic or adverse effects have been associated with large intakes of vitamin B 12 from food or supplements in healthy people . Doses as high as 1 mg (1000 mcg) daily by mouth or 1 mg monthly by intramuscular (IM) injection have been used to treat pernicious anemia , without significant side effects. When h igh doses of vitamin B 12 are given orally only a small percentage can be absorbed, which may explain its low toxicity. Because of the low toxicity of vitamin B 12 , no tolerable upper intake level ( UL ) was set by the Food and Nutrition Board in 1998 when the RDA was revised (5) .
Drug interactions

A number of drugs reduce the absorption of vitamin B 12 . Proton pump inhibitors (e.g., omeprazole and lansoprazole), used for therapy of Zollinger-Ellison syndrome and gastroesophageal reflux disease (GERD), markedly decrease stomach acid secretion required for the release of vitamin B 12 from food but not supplements . Long-term use of proton pump inhibitors has been found to decrease blood vitamin B 12 levels . However, vitamin B 12 deficiency does not generally develop until after at least three years of continuous therapy (22) . Another class of gastric acid inhibitors known as H 2 -receptor antagonists (e.g., Tagamet, Pepsid, Zantac), often used to treat peptic ulcer disease , has also been found to decrease the absorption of vitamin B 12 from food . Because inhibition of gastric acid secretion is not as prolonged as with proton pump inhibitors H 2 -receptor antagonists have not been found to cause overt vitamin B 12 deficiency even after long-term use (23) . Individuals taking drugs that inhibit gastric acid secretion should consider taking vitamin B 12 in the form of a supplement , because gastric acid is not required for its absorption. Other drugs found to inhibit the absorption of vitamin B 12 from food include cholestyramine (a bile acid -binding resin used in the treatment of high cholesterol ), chloramphenicol, neomycin ( antibiotics ), and colchicine (anti-gout). Metformin, a medication for individuals with type 2 (non-insulin dependent) diabetes, decreases vitamin B 12 absorption by tying up free calcium required for absorption of the IF- B 12 complex. This effect is correctable by drinking milk or taking calcium carbonate tablets along with food or supplements (4) . Previous reports that megadoses of vitamin C resulted in the destruction of vitamin B 12 have not been supported (24) and may have been an artifact of the assay used to measure vitamin B 12 levels (5) .

Nitrous oxide, a commonly used anesthetic inhibits both vitamin B 12 dependent enzymes and can produce many of the clinical features of vitamin B 12 deficiency, such as megaloblastic anemia or neuropathy . Because nitrous oxide is commonly used for surgery in the elderly, some experts feel vitamin B 12 deficiency should be ruled out prior to its use (, 7) .

Large doses of folic acid given to an individual with an undiagnosed vitamin B 12 deficiency could correct megaloblastic anemia without correcting the underlying vitamin B 12 deficiency , leaving the individual at risk of developing irreversible neurologic damage (5) . For this reason the Food and Nutrition Board of the Institute of Medicine advises that all adults limit their intake of folic acid (supplements and fortification) to 1000 mcg (1 mg) daily.
Linus Pauling Institute Recommendation

A varied diet should provide enough vitamin B 12 to prevent deficiency in most individuals 50 years of age and younger. Individuals over the age of 50, strict vegetarians, and women planning to become pregnant should take a multivitamin tablet daily or eat a fortified breakfast cereal, which would ensure a daily intake of 6 to 30 mcg of vitamin B 12 in a form that is easily absorbed .
Older adults (65 years and over)

Because vitamin B 12 malabsorption and vitamin B 12 deficiency are more common in older adults, some respected nutritionists recommend 100 to 400 mcg/day of supplemental vitamin B 12 , an amount provided by a number of vitamin B-complex supplements.

References

Written by:
Jane Higdon, Ph.D.
Linus Pauling Institute
Oregon State University

Reviewed by:
Jeffrey Blumberg, Ph.D., F.A.C.N.
Professor and Associate Director
Jean Mayer USDA Human Nutrition Research Center on Aging
Tufts University

Last updated 03/05/2003 Copyright 2000-2003 Linus Pauling Institute

Disclaimer

The Linus Pauling Institute Micronutrient Information Center provides scientific information on health aspects of micronutrients and phytochemicals for the general public. The information is made available with the understanding that the author and publisher are not providing medical, psychological, or nutritional counseling services on this site. The information should not be used in place of a consultation with a competent health care or nutrition professional.

The information on micronutrients and phytochemicals contained on this Web site does not cover all possible uses, actions, precautions, side effects, and interactions. It is not intended as medical advice for individual problems. Liability for individual actions or omissions based upon the contents of this site is expressly disclaimed.

Vitamin B 1 injections 10 vials 1 ml

Vitamin B 1 ( thiamin )

Thiamin (also spelled thiamine) is a water-soluble B-complex vitamin, previously known as vitamin B 1 or aneurine . Isolated and characterized in the 1930's, thiamin was one of the first organic compounds to be recognized as a vitamin . Thiamin occurs in the human body as free thiamin and its phosphorylated forms: thiamin monophosphate (TMP), thiamin triphosphate (TTP), and thiamin pyrophosphate (TPP), which is also known as thiamin diphosphate.
Function
Vitamin B 1: coenzyme function

Thiamin pyrophosphate (TPP) is a required coenzyme for a small number of very important enzymes . The synthesis of TPP from free thiamin requires magnesium , adenosine triphosphate ( ATP ), and the enzyme, thiamin pyrophosphokinase.

Pyruvate dehydrogenase, a-ketoglutarate dehydrogenase, and branched chain ketoacid (BCKA) dehydrogenase each comprise a different enzyme complex found within cellular organelles called mitochondria . They catalyze the decarboxylation of pyruvate, a-ketoglutarate, and branched-chain amino acids to form acetyl-coenzyme A, succinyl-coenzyme A, and derivatives of branched chain amino acids, respectively, all of which play critical roles in the production of energy from food . In addition to the thiamin coenzyme (TPP), each dehydrogenase complex requires a niacin -containing coenzyme (NAD), a riboflavin -containing coenzyme (FAD), and lipoic acid .

Transketolase catalyzes critical reactions in another metabolic pathway known as the pentose phosphate pathway. One of the most important intermediates of this pathway is ribose-5-phosphate, a phosphorylated 5-carbon sugar, required for the synthesis of the high-energy ribonucleotides, ATP and guanosine triphosphate ( GTP ), the nucleic acids , DNA and RNA , and the niacin-containing coenzyme NADPH, which is essential for a number of biosynthetic reactions . Because transketolase decreases early in thiamin deficiency, measurement of its activity in red blood cells has been used to assess thiamin nutritional status .
Vitamin B 1: non-coenzyme function

Thiamin triphosphate (TTP) is concentrated in nerve and muscle cells. Research in animals indicates that TTP activates membrane ion channels , possibly by phosphorylating them (4) . The flow of electrolytes like sodium or potassium in or out of nerve and muscle cells through membrane ion channels plays a role in nerve impulse conduction and voluntary muscle action. Impaired formation of TTP may play a role in the neurologic symptoms of severe thiamin deficiency.
Vitamin B 1: deficiency

Beriberi, the disease resulting from severe thiamin deficiency, was described in Chinese literature as early as 2600 B.C. Thiamin deficiency affects the cardiovascular, nervous, muscular, and gastrointestinal systems . Beriberi has been termed dry, wet, and cerebral, depending on the systems affected by severe thiamin deficiency .
Vitamin B 1: dry berberi

The main feature of dry (paralytic or nervous) beriberi is peripheral neuropathy . Early in the course of the neuropathy "burning feet syndrome" may occur. Other symptoms include abnormal (exaggerated) reflexes, diminished sensation and weakness in the legs and arms. Muscle pain and tenderness and difficulty rising from a squatting position have also been observed. Severely thiamin deficient individuals may experience seizures .
Vitamin B 1: wet beriberi

In addition to neurologic symptoms, wet (cardiac) beriberi is characterized by cardiovascular manifestations of thiamin deficiency, which include rapid heart rate, enlargement of the heart, severe swelling ( edema ), difficulty breathing, and ultimately congestive heart failure .
Vitamin B 1: cerebral beriberi

Cerebral beriberi may lead to Wernicke's encephalopathy and Korsakoff's psychosis. The diagnosis of Wernicke's encephalopathy is based on a "triad" of signs, which include abnormal eye movements, stance and gait abnormalities, and abnormalities in mental function, which may include a confused apathetic state or a profound memory disorder termed Korsakoff's amnesia or Korsakoff's psychosis. Thiamin deficiency affecting the central nervous system is referred to as Wernicke's disease when the amnesic state is not present and Wernicke-Korsakoff syndrome (WKS) when the amnesic symptoms are present along with the eye movement and gait disorders. Most WKS sufferers are alcoholics, although it has been observed in other disorders of gross malnutrition, including stomach cancer and AIDS. Administration of intravenous thiamin to WKS patients generally results in prompt improvement of the eye symptoms, but improvements in motor coordination and memory may be less, depending on how long the symptoms have been present. Recent evidence of increased immune cell activation and increased free radical production in the areas of the brain that are selectively damaged suggests that oxidative stress plays an important role in the neurologic pathology of thiamin deficiency .
Vitamin B 1: causes of thiamin deficiency

Thiamin deficiency may result from inadequate thiamin intake, an increased requirement for thiamin, excessive loss of thiamin from the body, consumption of anti-thiamin factors in food, or a combination of factors.
Vitamin B 1: inadequate intake

Inadequate consumption of thiamin is the main cause of thiamin deficiency in underdeveloped countries . Thiamin deficiency is common in low-income populations whose diets are high in carbohydrate and low in thiamin (e.g., milled or polished rice). Breast fed infants whose mothers are thiamin deficient are vulnerable to developing infantile beriberi. Alcoholism, which is associated with low intake of thiamin among other nutrients, is the primary cause of thiamin deficiency in industrialized countries.
Vitamin B 1: increased requirement

Conditions resulting in an increased requirement for thiamin include strenuous physical exertion, fever, pregnancy, breastfeeding, and adolescent growth. Such conditions place individuals with marginal thiamin intake at risk for developing symptomatic thiamin deficiency. Recently, malaria patients in Thailand were found to be severely thiamin deficient more frequently than non-infected individuals. Malarial infection leads to a large increase in the metabolic demand for glucose , as well as increased demand for the disposal of lactate. The stresses induced by malarial infection could exacerbate thiamin deficiency in individuals already predisposed . HIV -infected individuals, whether or not they had developed AIDS , were also found to be at increased risk for thiamin deficiency . The lack of association between thiamin intake and evidence of deficiency in these HIV-infected individuals suggested they had an increased requirement for thiamin.
Vitamin B 1: excessive loss

Excessive loss of thiamin may precipitate thiamin deficiency. Individuals with kidney failure requiring hemodialysis lose thiamin at an increased rate, and are at risk for thiamin deficiency . By increasing urinary flow, diuretics may prevent reabsorption of thiamin by the kidney and increase its excretion in the urine . Alcoholics who maintain a high fluid intake and urine flow rate may also experience increased loss of thiamin, exacerbating the effects of low thiamin intake .
Vitamin B 1: anti-thiamin factors (ATF)

The presence of anti-thiamin factors (ATF) in foods also contributes to the risk of thiamin deficiency. Certain plants contain ATF, which react with thiamin to form a product that is oxidized in the body, rendering it inactive. Consuming large amounts of tea and coffee (including decaffeinated), as well as chewing tea leaves and betel nut have been associated with thiamin depletion in humans due to the presence of ATF. Vitamin C and other antioxidants can protect thiamin in some foods by preventing its oxidation to an inactive form . Thiaminases are enzymes that break down thiamin in food. Individuals who habitually eat certain raw freshwater fish, raw shellfish, and ferns are at higher risk of thiamin deficiency because these foods contain a thiaminase, which would normally be inactivated by the heat used for cooking. An acute neurologic syndrome (seasonal ataxia) in Nigeria has been associated with thiamin deficiency precipitated by a thiaminase in African silkworms, a traditional high-protein food for some Nigerians .
Vitamin B 1: The Recommended Dietary Allowance (RDA)

The RDA for thiamin, revised in 1998, was based on the prevention of deficiency in generally healthy individuals .
Recommended Dietary Allowance (RDA) for Thiamin
Life Stage Age Males (mg/day) Females (mg/day)
Infants 0-6 months 0.2 (AI) 0.2 (AI)
Infants 7-12 months 0.3 (AI) 0.3 (AI)
Children 1-3 years 0.5 0.5
Children 4-8 years 0.6 0.6
Children 9-13 years 0.9 0.9
Adolescents 14-18 years 1.2 1.0
Adults 19 years and older 1.2 1.1
Pregnancy all ages - 1.4
Breastfeeding all ages - 1.4
Vitamin B 1: disease Treatment
Vitamin B 1: alzheimer's disease

Because thiamin deficiency can result in a form of dementia (Wernicke-Korsakoff syndrome), its relationship to Alzheimer's disease and other forms of dementia have been investigated. Several investigators found evidence of decreased activity of the thiamin pyrophosphate-dependent enzymes, a-ketoglutarate dehydrogenase and transketolase, in the brains of patients who died of Alzheimer's disease . Such findings are consistent with evidence of reduced glucose metabolism found on PET scans of the brains of Alzheimer's disease patients . The finding of decreased brain levels of thiamin pyrophophosphate (TPP) in the presence of normal levels of free thiamin and thiamin monophosphate (TMP) suggests that the decreased enzyme activity is not likely to be the result of thiamin deficiency, but rather of impaired synthesis of TPP . Presently, there is only slight evidence that thiamin supplements are of benefit in Alzheimer's disease. A double blind placebo -controlled study of 15 patients (10 completed the study) reported no beneficial effect of 3 grams of thiamin/day on cognitive decline over a 12-month period. A preliminary report from another study claimed a mild benefit of 3 to 8 grams of thiamin/day in dementia of Alzheimer's type in 1993, but no additional data from that study are available . A mild beneficial effect in patients with Alzheimer's disease was reported after 12 weeks of treatment with 100 milligrams/day of a thiamin derivative (thiamin tetrahydrofurfuryl disulfide), but this study was not placebo -controlled . A recent systematic review of randomized , double blind, placebo-controlled trials of thiamin in patients with dementia of Alzheimer's type found no evidence that thiamin was a useful treatment for the symptoms of Alzheimer's disease .
Vitamin B 1: congestive heart failure (CHF)

Severe thiamin deficiency (wet beriberi) can lead to impaired cardiac function and ultimately congestive heart failure (CHF). Although cardiac manifestations of beriberi are rarely encountered in industrialized countries, CHF due to other causes is common, especially in the elderly. Diuretics used in the treatment of CHF, notably furosemide (Lasix), have been found to increase thiamin excretion, potentially leading to marginal thiamin deficiency. A number of studies have examined thiamin nutritional status in CHF patients and most found a fairly low incidence of thiamin deficiency, as measured by assays of transketolase activity. As in the general population, older CHF patients were found to be at higher risk of thiamin deficiency . An important measure of cardiac function in CHF is the left ventricular ejection fraction (LVEF), which can be assessed by echocardiography . In a randomized double-blind study of 30 CHF patients, all of whom had been taking furosemide for at least 3 months, intravenous (IV) thiamin therapy (200 mg/day) for 7 days resulted in an improved LVEF compared to IV placebo . When all 30 of the CHF patients in that study subsequently received 6 weeks of oral thiamin therapy (200 mg/day) the average LVEF improved by 22%. This finding may be significant because improvements in LVEF have been associated with improved survival in CHF patients . Conclusions that can be drawn from the studies published to date are limited due to small sample sizes, lack of randomization in some studies, and a need for more precise assays of thiamin nutritional status. Presently, the role of thiamin supplementation in maintaining cardiac function in CHF patients remains controversial.
Vitamin B 1: cancer

Thiamin deficiency has been observed in some cancer patients with rapidly growing tumors. Recent research in cell culture and animal models indicates that rapidly dividing cancer cells have a high requirement for thiamin . All rapidly dividing cells require nucleic acids at an increased rate, but some cancer cells appear to rely heavily on the TPP-dependent enzyme, transketolase, to provide the ribose-5-phosphate necessary for nucleic acid synthesis . Thiamin supplementation in cancer patients is common to prevent thiamin deficiency, but some investigators caution that too much thiamin may fuel the growth of some malignant tumors. These investigators suggest that thiamin supplementation be reserved for those cancer patients that are actually thiamin deficient . Presently, there is no evidence available from studies in humans to support or refute this theory. However, it would be prudent for individuals with cancer who are considering thiamin supplementation to discuss this issue with the clinician managing their cancer therapy.
Vitamin B 1: sources
Vitamin B 1: food sources

A varied diet should provide most individuals with adequate thiamin to prevent deficiency. In the U.S. the average dietary thiamin intake for young adult men is about 2 mg/day and 1.2 mg/day for young adult women. A survey of people over the age of 60 found an average dietary thiamin intake of 1.4 mg/day for men and 1.1 mg/day for women . However, institutionalization and poverty increase the likelihood of inadequate thiamin intake in the elderly .Whole grain cereals, legumes (e.g., beans and lentils), nuts, lean pork, and yeast are rich sources of thiamin . Because most of the thiamin is lost during the production of white flour and polished (milled) rice, white rice and foods made from white flour (e.g., bread and pasta) are fortified with thiamin. A number of thiamin-rich foods are listed in the table below along with their thiamin content in milligrams (mg). For more information on the nutrient content of foods you eat frequently, search the USDA food composition database .
Food Serving Thiamin (mg)
Lentils (cooked) 1/2 cup 0.17
Peas (cooked) 1/2 cup 0.21
Long grain brown rice (cooked) 1 cup 0.19
Long grain white rice, enriched (cooked) 1 cup 0.26
Long grain white rice, unenriched (cooked) 1 cup 0.03
Whole wheat bread 1 slice 0.10
White bread , enriched 1 slice 0.12
Fortified breakfast cereal 1 cup 0.5-2.0
Wheat germ breakfast cereal 1 cup 1.89
Pork, lean (cooked) 3 ounces* 0.74
Brazil nuts 1 ounce 0.28
Pecans 1 ounce 0.13
Spinach ( cooked) 1/2 cup 0.09
Orange 1 fruit 0.11
Cantaloupe 1/2 fruit 0.10
Milk 1 cup 0.10
Egg (cooked) 1 large 0.03

*3 ounces of meat is a serving about the size of a deck of cards
Vitamin B 1: supplements

Thiamin is available in nutritional supplements and for fortification as thiamin hydrochloride and thiamin nitrate .
Vitamin B 1: safety
Vitamin B 1: toxicity

The Food and Nutrition Board did not set a tolerable upper level ( UL ) of intake for thiamin because there are no known toxic effects from the consumption of excess thiamin in food or through long-term oral supplementation (up to 200 mg/day). A small number of life threatening anaphylactic reactions have been observed with large intravenous doses of thiamin. However, anaphylactic reactions are the result of an overwhelming allergic response rather than a toxic effect of thiamin .
Vitamin B 1: drug interactions

Reduced blood levels of thiamin have been reported in individuals with seizure disorders (epilepsy) taking the anticonvulsant medication, phenytoin, for long periods of time . 5-Fluorouracil, a drug used in cancer therapy, inhibits the phosphorylation of thiamin to thiamin pyrophosphate (TPP) . Diuretics , especially furosemide (Lasix), may increase the risk of thiamin deficiency in individuals with marginal thiamin intake due to increased urinary excretion of thiamin .
Vitamin B 1: linus Pauling Institute Recommendation

The Linus Pauling Institute supports the recommendation by the Food and Nutrition Board of 1.2 mg of thiamin/day for men and 1.1 mg/day for women. A varied diet should provide enough thiamin for most people. Following the Linus Pauling Institute recommendation to take a daily multivitamin/multimineral supplement, containing 100 % of the Daily Values (DV), will ensure an intake of at least 1.5 mg of thiamin/day.
Vitamin B 1: older adults (65 years and older)

Presently, there is no evidence that the requirement for thiamin is increased in older adults, but some studies have found inadequate dietary intake and thiamin insufficiency to be more common in elderly populations . Thus, it would be prudent for older adults to take a multivitamin / multimineral supplement, which will generally provide at least 1.5 mg of thiamin/day.

References

Written by:
Jane Higdon, Ph.D.
Linus Pauling Institute
Oregon State University

Reviewed by:
Charles K. Singleton, Ph.D.
Professor
Department of Biological Sciences
Vanderbilt University

Last updated 09/23/2002 Copyright 2000-2002 Linus Pauling Institute

Disclaimer

The Linus Pauling Institute Micronutrient Information Center provides scientific information on health aspects of micronutrients and phytochemicals for the general public. The information is made available with the understanding that the author and publisher are not providing medical, psychological, or nutritional counseling services on this site. The information should not be used in place of a consultation with a competent health care or nutrition professional.

The information on micronutrients and phytochemicals contained on this Web site does not cover all possible uses, actions, precautions, side effects, and interactions. It is not intended as medical advice for individual problems. Liability for individual actions or omissions based upon the contents of this site is expressly disclaimed.

Vitamin B 6 injections 10vials 1 ml

Vitamin B 6

Vitamin B 6 is a water-soluble vitamin that was first isolated in the 1930's. There are six forms of vitamin B 6 : pyridoxal (PL), pyridoxine (PN), pyridoxamine (PM), and their phosphate derivatives: pyridoxal 5'-phosphate (PLP), pyridoxine 5'-phosphate (PNP), and pridoxamine 5'-phospate (PMP). PLP is the active coenzyme form, and has the most importance in human metabolism .
Vitamin B 6: function

Vitamin B 6 must be obtained from the diet because humans cannot synthesize it, and the coenzyme , PLP plays a vital role in the function of approximately 100 enzymes that catalyze essential chemical reactions in the human body . For example, PLP functions as a coenzyme for glycogen phosphorylase, an enzyme that catalyzes the release of glucose stored in the muscle as glycogen . Much of the PLP in the human body is found in muscle bound to glycogen phosphorylase. PLP is also a coenzyme for reactions used to generate glucose from amino acids , a process known as gluconeogenesis .
Vitamin B 6: nervous system function

The synthesis of the neurotransmitter , serotonin, from the amino acid, tryptophan, in the brain is catalyzed by a PLP-dependent enzyme. Other neurotransmitters such as dopamine, norepinephrine and gamma-aminobutyric acid (GABA) are also synthesized using PLP-dependent enzymes .
Vitamin B 6: red blood cell formation and function

PLP functions as a coenzyme in the synthesis of heme, a component of hemoglobin . Hemoglobin is found in red blood cells and is critical to their ability to transport oxygen throughout the body. Both PL and PLP are able to bind to the hemoglobin molecule and affect its ability to pick up and release oxygen. However, the impact of this on normal oxygen delivery to tissues is not known.
Vitamin B 6: niacin formation

The human requirement for another vitamin, niacin , can be met in part by the conversion of the dietary amino acid, tryptophan, to niacin, as well as through dietary intake. PLP is a coenzyme for a critical reaction in the synthesis of niacin from tryptophan. Thus, adequate vitamin B 6 decreases the requirement for niacin in the diet .
Vitamin B 6: hormone function

Steroid hormones , such as estrogen and testosterone, exert their effects in the body by binding to steroid hormone receptors in the nucleus of the cell and altering gene transcription . PLP binds to steroid receptors in such a manner as to inhibit the binding of steroid hormones, thus decreasing their effects. The binding of PLP to steroid receptors for estrogen, progesterone, testosterone, and other steroid hormones suggest that the vitamin B 6 status of an individual may have implications for diseases affected by steroid hormones, such as breast cancer and prostate cancer .
Vitamin B 6: nucleic acid synthesis

PLP serves as a coenzyme for a key enzyme involved in the mobilization of single-carbon functional groups (one-carbon metabolism). Such reactions are involved in the synthesis of nucleic acids . The effect of vitamin B 6 deficiency on immune system function may be partly related to the role of PLP in one-carbon metabolism .
Vitamin B 6 deficiency

Severe deficiency of vitamin B 6 is uncommon. Alcoholics are thought to be most at risk of vitamin B 6 deficiency, due to a low intake and impaired metabolism of the vitamin. In the early 1950's seizures were observed in infants as a result of severe vitamin B 6 deficiency due to an error in the manufacture of infant formula. Abnormal electroencephalogram (EEG) patterns have been noted in some studies of vitamin B 6 deficiency. Other neurologic symptoms noted in severe vitamin B 6 deficiency include irritability, depression, and confusion; additional symptoms include inflammation of the tongue, sores or ulcers of the mouth, and ulcers of the skin at the corners of the mouth .
Vitamin B 6:The Recommended Dietary Allowance ( RDA )

Because vitamin B 6 is involved in so many aspects of metabolism, several factors are likely to affect an individual's requirement for vitamin B 6 . Of those factors, protein intake has been studied the most. Increased dietary protein results in an increased requirement for vitamin B 6 , probably because PLP is a coenzyme for many enzymes involved in amino acid metabolism . Unlike previous recommendations, the Food and Nutrition Board (FNB) of the Institute of Medicine did not express the most recent RDA for vitamin B6 in terms of protein intake, although the relationship was considered in setting the RDA . The current RDA was revised by the Food and Nutrition Board (FNB) in 1998 and is presented in the table below.
Recommended Dietary Allowance (RDA) for Vitamin B 6
Life Stage Age Males (mg/day) Females (mg/day)
Infants 0-6 months 0.1 (AI) 0.1 (AI)
Infants 7-12 months 0.3 (AI) 0.3 (AI)
Children 1-3 years 0.5 0.5
Children 4-8 years 0.6 0.6
Children 9-13 years 1.0 1.0
Adolescents 14-18 years 1.3 1.2
Adults 19-50 years 1.3 1.3
Adults 51 years and older 1.7 1.5
Pregnancy all ages - 1.9
Breastfeeding all ages - 2.0
Vitamin B 6: DISEASE PREVENTION
Vitamin B 6: homocysteine and cardiovascular disease

Even moderately elevated levels of homocysteine in the blood have been associated with increased risk for cardiovascular disease, including heart disease and stroke . When we digest protein, amino acids , including methionine, are released. Homocysteine is an intermediate in the metabolism of methionine. Healthy individuals utilize two different pathways to metabolize homocysteine. One pathway results in the conversion of homocysteine back to methionine, and is dependent on folic acid and vitamin B 12 . The other pathway converts homocysteine to another amino acid, cysteine, and requires two vitamin B 6 (PLP)-dependent enzymes. Thus, the amount of homocysteine in the blood is regulated by at least three vitamins: folic acid, vitamin B 12 , and vitamin B 6 . Several large observational studies have demonstrated an association between low vitamin B 6 intake or status with increased blood homocysteine levels and increased risk of cardiovascular diseases. A large prospective study found the risk of heart disease in women who consumed, on average, 4.6 mg of vitamin B 6 daily to be only 67% of the risk in women who consumed an average of 1.1 mg daily . Another large prospective study found higher plasma levels of PLP to be associated with decreased risk of cardiovascular disease, independent of homocysteine levels . In contrast to folic acid supplementation, studies of vitamin B 6 supplementation alone have not resulted in significant decreases of basal (fasting) levels of homocysteine. However, vitamin B 6 supplementation has been found effective in lowering blood homocysteine levels after an oral dose of methionine (methionine load test) was given , suggesting it may play a role in the metabolism of homocysteine after meals.
Vitamin B 6: immune function

Low vitamin B 6 intake and nutritional status have been associated with impaired immune function, especially in the elderly. Decreased production of immune system cells known as lymphocytes , as well as decreased production of an important immune system protein called interleukin-2, have been measured in vitamin B 6 deficient individuals. Restoration of adequate vitamin B 6 status resulted in normalization of the lymphocyte proliferation and interleukin-2 production, suggesting that adequate vitamin B 6 intake is important for optimal immune system function in older individuals . However, one study found that the amount of vitamin B 6 required to reverse these immune system impairments in the elderly was 2.9 mg/day for men and 1.9 mg/day for women, more than the current RDA .
Vitamin B 6: cognitive function

A few recent studies have demonstrated an association between declines in cognitive function or Alzheimer's disease in the elderly and inadequate nutritional status of folic acid, vitamin B 12 , and vitamin B 6 and thus, elevated levels of homocysteine . One observational study found higher plasma vitamin B 6 levels to be associated with better performance on two measures of memory, but unrelated to performance on 18 other cognitive tests . It is presently unclear whether marginal B vitamin deficiencies, which are relatively common in the elderly, contribute to age-associated declines in cognitive function or whether both result from processes associated with aging and/or disease.
Vitamin B 6: kidney stones

A large prospective study examined the relationship between vitamin B 6 intake and the occurrence of symptomatic kidney stones in women. In a group of more than 85,000 women without a prior history of kidney stones, followed over 14 years, those who consumed 40 mg or more of vitamin B 6 daily had only two thirds the risk of developing kidney stones compared with those who consumed 3 mg or less . However, in a group of more than 45,000 men followed over 6 years, no association was found between vitamin B 6 intake and the occurrence of kidney stones . Limited data have shown that supplementation of vitamin B 6 at levels higher than the tolerable upper intake level (100 mg) decreased elevated urinary oxalate levels, an important determinant of calcium oxalate kidney stone formation, in some individuals. However, it is less clear that supplementation actually resulted in decreased formation of calcium oxalate kidney stones. Presently, the relationship between vitamin B 6 intake and the risk of developing kidney stones requires further study before any recommendation can be made.
Vitamin B 6: disease Treatment

Vitamin B 6 supplements at pharmacologic doses (i.e., doses much larger than those needed to prevent deficiency) have been used in an attempt to treat a wide variety of conditions, some of which are discussed below. In general, well designed, placebo -controlled studies have shown little evidence of benefit from large supplemental doses of vitamin B 6 .
Vitamin B 6: side effects of oral contraceptives

Because vitamin B 6 is required for the metabolism of the amino acid tryptophan, the tryptophan load test (an assay of tryptophan metabolites after an oral dose of tryptophan) was used as a functional assessment of vitamin B 6 status. Abnormal tryptophan load tests in women taking high-dose oral contraceptives in the 1960's and 1970's suggested that these women were vitamin B 6 deficient. The abnormal results in the tryptophan load test led a number of clinicians to prescribe high doses (100-150 mg/day) of vitamin B 6 to women in order to relieve depression and other side effects sometimes experienced with oral contraceptives. However, most other indices of vitamin B 6 status were normal in women on high-dose oral contraceptives, and it is likely that the abnormality in tryptophan metabolism was not due to vitamin B 6 deficiency . A more recent study of women on the low-dose oral contraceptives prescribed currently showed no benefit of up to 150 mg/day of vitamin B 6 (pyridoxine) over a placebo in the prevention of side effects, such as nausea, vomiting, dizziness, depression, and irritability .
Vitamin B 6: premenstrual syndrome (PMS)

The use of vitamin B 6 to relieve the side effects of high-dose oral contraceptives led to the use of vitamin B 6 in the treatment of premenstrual syndrome (PMS). PMS refers to a cluster of symptoms, including but not limited to fatigue, irritability, moodiness/depression, fluid retention, and breast tenderness, that begin sometime after ovulation (mid-cycle) and subside with the onset of menstruation (the monthly period). A review of twelve placebo-controlled double-blind trials of vitamin B 6 in PMS concluded that evidence for a beneficial effect was weak . A more recent review of 25 studies of vitamin B 6 and PMS suggested that doses of vitamin B 6 up to 100 mg/day may be of value, but conclusions were limited by the poor quality of most of the studies evaluated .
Vitamin B 6: depression

Because a key enzyme in the synthesis of the neurotransmitters , serotonin and norepinephrine, is PLP-dependent, it has been suggested that vitamin B-6 deficiency may lead to depression. However, clinical trials have not provided evidence that vitamin B-6 supplementation is effective in the treatment of depression .
Vitamin B 6: morning sickness (nausea and vomiting in pregnancy)

Vitamin B 6 has been used since the 1940's to treat nausea during pregnancy. Vitamin B 6 was included in the medication, Bendectin, which was prescribed for the treatment of morning sickness, and later withdrawn from the market due to unproven concerns that it increased the risk of birth defects. Vitamin B6 itself is considered safe during pregnancy, and has been used in pregnant women without any evidence of fetal harm . The results of two double-blind placebo-controlled trials that used 25 mg of pyridoxine every 8 hrs for 3 days or 10 mg of pyridoxine every 8 hrs for 5 days suggest vitamin B 6 may be beneficial in alleviating morning sickness. Each study found a slight but significant reduction in nausea or vomiting in pregnant women. A recent systematic review of placebo-controlled trials for nausea of early pregnancy found vitamin B 6 to be somewhat effective . However, it should be noted that morning sickness also resolves without any treatment, making it difficult to perform well-controlled trials.
Vitamin B 6: carpal tunnel syndrome

Carpal tunnel syndrome causes numbness, pain, and weakness of the hand and fingers due to compression of the median nerve at the wrist. It may result from repetitive stress injury of the wrist or from soft tissue swelling, which sometimes occurs with pregnancy or hypothyroidism . Several early studies by the same investigator suggested that vitamin B 6 status was low in individuals with carpal tunnel syndrome and that supplementation with 100-200 mg/day over several months was beneficial . A recent study found decreased blood levels of PLP to be associated with increased pain, tingling, and nocturnal wakening, all symptoms of carpal tunnel syndrome, in men who were not taking vitamin supplements . Studies using electrophysiological measurements of median nerve conduction have generally failed to find an association between vitamin B 6 deficiency and carpal tunnel syndrome. While a few trials have noted some symptomatic relief with vitamin B 6 supplementation, double-blind placebo-controlled trials have not generally found vitamin B 6 to be effective in treating carpal tunnel syndrome .
Vitamin B 6: sources
Vitamin B 6: food sources

Surveys in the U.S. have shown that dietary intake of vitamin B 6 averages about 2 mg/day for men and 1.5 mg/day for women. A survey of elderly individuals found that men and women over 60 consumed about 1.2 mg/day and 1.0 mg/day, respectively, both less than the current RDA. Certain plant foods contain a unique form of vitamin B 6 called pyridoxine glucoside. This form of vitamin B 6 appears to be only about half as bioavailable as vitamin B 6 from other food sources or supplements. Vitamin B 6 in a mixed diet has been found to be approximately 75% bioavailable . In most cases, including foods in the diet that are rich in vitamin B 6 should supply enough to prevent deficiency. However, those who follow a very restricted vegetarian diet might need to increase their vitamin B 6 intake by eating food, fortified with vitamin B 6 , or by taking a supplement. Some foods that are relatively rich in vitamin B 6 and their vitamin B 6 content in milligrams (mg) are listed in the table below. For more information on the nutrient content of foods you eat frequently, search the USDA food composition database .

Food


Serving
Vitamin B 6 (mg)
Fortified cereal 1 cup 0.5-2.5
Banana 1 medium 0.68
Salmon 3 ounces* 0.48
Turkey, without skin 3 ounces 0.39
Chicken, light meat without skin 3 ounces 0.46
Potato, baked, with skin 1 medium 0.70
Spinach, cooked 1 cup 0.44
Hazelnuts, dry roasted 1 ounce 0.18
Vegetable juice cocktail 6 ounces 0.25

*A 3-ounce serving of meat or fish is about the size of a deck of cards.
Vitamin B 6: supplements

Vitamin B 6 is available as pyridoxine hydrochloride in multivitamin, vitamin B-complex, and vitamin B 6 supplements .
Vitamin B 6: safety
Vitamin B 6: toxicity

Because adverse effects have only been documented from vitamin B 6 supplements and never from food sources, only the supplemental form of vitamin B 6 (pyridoxine) is discussed with respect to safety. Although vitamin B 6 is a water-soluble vitamin and is excreted in the urine, very high doses of pyridoxine over long periods of time may result in painful neurological symptoms known as sensory neuropathy . Symptoms include pain and numbness of the extremities, and in severe cases difficulty walking. Sensory neuropathy typically develops at doses of pyridoxine in excess of 1,000 mg per day. However, there have been a few case reports of individuals who developed sensory neuropathies at doses of less than 500 mg daily over a period of months. None of the studies, in which an objective neurological examination was performed, found evidence of sensory nerve damage at intakes of pyridoxine below 200 mg/day . In order to prevent sensory neuropathy in virtually all individuals, the Food and Nutrition Board of the Institute of Medicine set the tolerable upper intake level ( UL ) for pyridoxine at 100 mg/day for adults (see table below) . Because placebo-controlled studies have generally failed to show therapeutic benefits of high doses of pyridoxine, there is little reason to exceed the UL of 100 mg/day.
Tolerable Upper Intake Level (UL) for Vitamin B 6
Age Group UL (mg/day)
Infants 0-12 months Not possible to establish*
Children 1-3 years 30
Children 4-8 years 40
Children 9-13 years 60
Adolescents 14-18 years 80
Adults 19 years and older 100

*Source of intake should be from food and formula only.
Vitamin B 6: drug interactions

Certain medications, interfere with the metabolism of vitamin B 6 , and may result in deficiency if individuals taking such medications are not given supplemental vitamin B 6 . The anti-tuberculosis medications, isoniazid and cycloserine, the metal chelator, penicillamine, and anti parkinsonian drugs, including L-dopa, form complexes with vitamin B 6 , creating a functional deficiency. The efficacy of other medications may be altered by high doses of vitamin B 6 . High doses of vitamin B 6 have been found to decrease the efficacy of the anticonvulsants , phenobarbitol and phenytoin, and L-dopa .
Vitamin B 6: linus Pauling Institute Recommendation

Metabolic studies suggest that young women require 0.02 mg of vitamin B 6 per gram of protein consumed daily . Using the upper boundary for acceptable levels of protein intake for women (100 grams/day), the daily requirement for young women would be calculated at 2.0 mg daily. Older adults may also require at least 2.0 mg/day. For these reasons, the Linus Pauling Institute recommends that all adults consume at least 2.0 mg of vitamin B 6 daily. Following the Linus Pauling Institute recommendation to take a daily multivitamin / mineral supplement containing 100 % of the Daily Value for vitamin B 6 will ensure an intake of at least 2.0 mg/day of vitamin B 6. Although a vitamin B 6 intake of 2.0 mg daily is slightly higher than the most recent RDA , it is 50 times less than the tolerable upper intake level (UL) set by the Food and Nutrition Board .
Vitamin B 6: older adults (65 years and older)

Metabolic studies have indicated that the requirement for vitamin B 6 in older adults is approximately 2.0 mg daily , and could be higher if the effect of marginally deficient intakes of vitamin B 6 on immune function and homocysteine levels are clarified. Despite evidence that the requirement for vitamin B 6 may be slightly higher in older adults, several surveys have found that over half of individuals over age 60 consume less than the current RDA (1.7 mg/day for men and 1.5 mg/day for women). For these reasons, the Linus Pauling Institute recommends that older adults take a multivitamin / multimineral supplement, which generally provides at least 2.0 mg of vitamin B 6 daily.

References

Written by:
Jane Higdon, Ph.D.
Linus Pauling Institute
Oregon State University

Reviewed by:
James E. Leklem, Ph.D.
Professor, Emeritus
Department of Nutrition and Food Management
Oregon State University

Last updated 2/19/2002 Copyright 2000-2002 Linus Pauling Institute

Disclaimer

The Linus Pauling Institute Micronutrient Information Center provides scientific information on health aspects of micronutrients and phytochemicals for the general public. The information is made available with the understanding that the author and publisher are not providing medical, psychological, or nutritional counseling services on this site. The information should not be used in place of a consultation with a competent health care or nutrition professional.

The information on micronutrients and phytochemicals contained on this Web site does not cover all possible uses, actions, precautions, side effects, and interactions. It is not intended as medical advice for individual problems. Liability for individual actions or omissions based upon the contents of this site is expressly disclaimed.

Vitamin - C Injection

Vitamin C

Vitamin C, also known as ascorbic acid, is a water-soluble vitamin . Unlike most mammals, humans do not have the ability to make their own vitamin C. Therefore, we must obtain vitamin C through our diet.
Vitamin C: function

Vitamin C is required for the synthesis of collagen, an important structural component of blood vessels, tendons, ligaments, and bone. Vitamin C also plays an important role in the synthesis of the neurotransmitter , norepinephrine. Neurotransmitters are critical to brain function and are known to affect mood. In addition, vitamin C is required for the synthesis of carnitine , a small molecule that is essential for the transport of fat to cellular organelles called mitochondria , for conversion to energy . Recent research also suggests that vitamin C is involved in the metabolism of cholesterol to bile acids , which may have implications for blood cholesterol levels and the incidence of gallstones .

Vitamin C is also a highly effective antioxidant . Even in small amounts vitamin C can protect indispensable molecules in the body, such as proteins, lipids (fats), carbohydrates, and nucleic acids (DNA and RNA) from damage by free radicals and reactive oxygen species that can be generated during normal metabolism as well as through exposure to toxins and pollutants (e.g. smoking). Vitamin C may also be able to regenerate other antioxidants such as vitamin E .
Vitamin C: deficiency
Vitamin C: scurvy

Severe vitamin C deficiency has been known for many centuries as the potentially fatal disease, scurvy . By the late 1700's the British navy was aware that scurvy could be cured by eating oranges or lemons, even though vitamin C would not be isolated until the early 1930's. Symptoms of scurvy include bleeding and bruising easily, hair and tooth loss, joint pain and swelling. Such symptoms appear to be related to the weakening of blood vessels, connective tissue, and bone, which contain collagen. Early symptoms of scurvy such as fatigue may result from diminished levels of carnitine , needed to derive energy from fat, or decreased synthesis of the neurotransmitter norepinephrine (see Function ). Scurvy is rare in developed countries because it can be prevented by as little as 10 mg of vitamin C daily . However, recent cases have occurred in children and the elderly on very restricted diets .
Vitamin C: the Recommended Dietary Allowance (RDA)

In the U.S., the recommended dietary allowance ( RDA ) for vitamin C was recently revised upward from 60 mg daily for men and women. The RDA continues to be based primarily on the prevention of deficiency disease, rather than the prevention of chronic disease and the promotion of optimum health. The recommended intake for smokers is 35 mg/day higher than for nonsmokers, because smokers are under increased oxidative stress from the toxins in cigarette smoke and generally have lower blood levels of vitamin C .
Recommended Dietary Allowance (RDA) for Vitamin C
Life Stage Age Males (mg/day) Females (mg/day)
Infants 0-6 months 40 ( AI ) 40 (AI)
Infants 7-12 months 50 (AI) 50 (AI)
Children 1-3 years 15 15
Children 4-8 years 25 25
Children 9-13 years 45 45
Adolescents 14-18 years 75 65
Adults 19 years and older 90 75
Smokers 19 years and older 125 110
Pregnancy 18 years and younger - 80
Pregnancy 19-years and older - 85
Breastfeeding 18 years and younger - 115
Breastfeeding 19 years and older - 120
Vitamin C: disease Prevention

The amount of vitamin C required to prevent chronic disease appears to be more than that required for prevention of scurvy. Much of the information regarding vitamin C and the prevention of chronic disease is based on prospective studies , in which vitamin C intake is assessed in large numbers of people who are followed over time to determine whether they develop specific chronic diseases.
Vitamin C: cardiovascular Disease
Vitamin C: coronary Heart Disease

Until recently, the results of most prospective studies indicated that low or deficient intakes of vitamin C were associated with an increased risk of cardiovascular diseases and that modest dietary intakes of about 100 mg/day were sufficient for maximum reduction of cardiovascular disease risk among nonsmoking men and women . In addition, several studies had failed to find significant reductions in the risk of coronary heart disease (CHD) among vitamin C supplement users in well-nourished populations . One notable exception was the First National Health and Nutrition Examination Study (NHANES I) Epidemiologic Follow-up Study . This study found that the risk of death from cardiovascular diseases was 42% lower in men and 25% lower in women who consumed more than 50 mg/day of dietary vitamin C and who regularly took vitamin C supplements, corresponding to a total vitamin C intake of about 300 mg/day . Results from the Nurses' Health Study, based on the follow-up of more than 85,000 women over 16 years, also suggest that higher vitamin C intakes may be cardioprotective . In this study, vitamin C intakes of more than 359 mg/day from diet plus supplements or supplement use itself were associated with a 27-28% reduction in CHD risk. However, in those women who did not take vitamin C supplements, dietary vitamin C intake was not significantly associated with CHD risk. More recently, a pooled analysis of 9 prospective cohort studies , including more than 290,000 adults who were free of CHD at baseline and followed for an average of 10 years, found that those who took more than 700 mg/day of supplemental vitamin C had a 25% lower risk of CHD than those who did not take vitamin C supplements . Data from the National Institutes of Health (NIH) indicate that plasma and circulating cells in healthy, young subjects became fully saturated with vitamin C at a dose of about 400 mg/day . The results of the pooled analysis of prospective cohort studies suggest that maximum reduction of CHD risk may require vitamin C intakes high enough to saturate plasma and circulating cells, and thus the vitamin C body pool .
Vitamin C: stroke

With respect to vitamin C and cerebrovascular disease , a prospective study that followed more than 2,000 residents of a rural Japanese community for 20 years found that the risk of stroke in those with the highest serum levels of vitamin C was 29% lower than in those with the lowest serum levels of vitamin C . Additionally, the risk of stroke in those who consumed vegetables 6-7 days of the week was 54% lower than in those who consumed vegetables 0-2 days of the week. In this population, serum levels of vitamin C were highly correlated with fruit and vegetable intakes. Therefore, as in many studies of vitamin C intake and cardiovascular disease risk, it is difficult to separate the effects of vitamin C on stroke risk from the effects of other components of fruits and vegetables, emphasizing the benefits of a diet rich in fruits and vegetables.
Vitamin C: cancer

A large number of studies have shown that increased consumption of fresh fruits and vegetables is associated with a reduced risk for most types of cancer . Such studies are the basis for dietary guidelines endorsed by the U.S. Department of Agriculture and the National Cancer Institute, which recommend at least 5 servings of fruits and vegetables per day. A number of case-control studies have investigated the role of vitamin C in cancer prevention. Most have shown that higher intakes of vitamin C are associated with decreased incidence of cancers of the mouth, throat and vocal chords, esophagus , stomach, colon -rectum, and lung. Because the possibility of bias is greater in case-control studies , prospective studies are generally given more weight in the evaluation of the effect of nutrient intake on disease. In general, prospective studies in which the lowest intake group consumed more than 86 mg of vitamin C daily have not found differences in cancer risk, while studies finding significant cancer risk reductions found them in people consuming at least 80 to 110 mg of vitamin C daily .

A prospective study of 870 men over a period of 25 years found that those who consumed more than 83 mg of vitamin C daily had a striking 64% reduction in lung cancer compared with those who consumed less than 63 mg per day . Although most large prospective studies found no association between breast cancer and vitamin C intake, two recent studies found dietary vitamin C intake to be inversely associated with breast cancer risk in certain subgroups. In the Nurses' Health Study, premenopausal women with a family history of breast cancer who consumed an average of 205 mg/day of vitamin C from foods had a 63% lower risk of breast cancer than those who consumed an average of 70 mg/day . In the Swedish Mammography Cohort, women who were overweight and consumed an average of 110 mg/day of vitamin C had a 39% lower risk of breast cancer compared to overweight women who consumed an average of 31 mg/day . A number of observational studies have found increased dietary vitamin C intake to be associated with decreased risk of stomach cancer, and laboratory experiments indicate that vitamin C inhibits the formation of carcinogenic compounds in the stomach. Infection with the bacteria, helicobacter pylori ( H. pylori ) is known to increase the risk of stomach cancer and also appears to lower the vitamin C content of stomach secretions. Although two intervention studies did not find a decrease in the occurrence of stomach cancer with vitamin C supplementation , more recent research suggests that vitamin C supplementation may be a useful addition to standard H. pylori eradication therapy in reducing the risk of gastric cancer .
Vitamin C: cataracts

Cataracts are a leading cause of visual impairment throughout the world. In the U.S., cataract-related expenditure is estimated to exceed 3 billion dollars annually . Cataracts occur more frequently and become more severe as people age. Decreased vitamin C levels in the lens of the eye have been associated with increased severity of cataracts in humans. Some, but not all, studies have observed increased dietary vitamin C intake and increased blood levels of vitamin C to be associated with decreased risk of cataracts. Those studies that have found a relationship suggest that vitamin C intake may have to be higher than 300 mg/day for a number of years before a protective effect can be detected . Recently, a 7-year controlled intervention trial of a daily antioxidant supplement containing 500 mg of vitamin C, 400 IU of vitamin E, and 15 mg of beta-carotene in 4,629 men and women found no difference between the antioxidant combination and a placebo on the development and progression of age-related cataracts . Therefore, the relationship between vitamin C intake and the development of cataracts requires further clarification before specific recommendations can be made.
Vitamin C: lead toxicity

Although the use of lead paint and leaded gasoline has been discontinued in the U.S., lead toxicity continues to be a significant health problem, especially in children living in urban areas. Abnormal growth and development has been observed in infants of women exposed to lead during pregnancy, while children who are chronically exposed to lead are more likely to develop learning disabilities, behavioral problems, and to have low IQs. In adults, lead toxicity may result in kidney damage and high blood pressure. In a study of 747 older men, blood lead levels were significantly higher in those who reported total dietary vitamin C intakes averaging less than 109 mg/day compared to men who reported higher vitamin C intakes . A much larger study of 19,578 people, including 4,214 children from 6 to 16 years of age, found higher serum vitamin C levels to be associated with significantly lower blood lead level . An intervention trial that examined the effects of vitamin C supplementation on blood lead levels in 75 adult male smokers found that 1,000 mg/day of vitamin C resulted in significantly lower blood lead levels over a 4-week treatment period compared to placebo . A lower dose of 200 mg/day did not significantly affect blood lead levels, despite the finding that serum vitamin C levels were not different than those of the group that took 1,000 mg/day. The mechanism for the relationship between vitamin C intake and blood lead levels is not known, although it has been postulated that vitamin C may inhibit intestinal absorption or enhance urinary excretion of lead.
Vitamin C: disease Treatment

Cardiovascular Disease
Vitamin C: vasodilation

The ability of blood vessels to relax or dilate is compromised in individuals with atherosclerosis . The damage to the heart muscle caused by a heart attack and damage to the brain caused by a stroke is related, in part, to the inability of blood vessels to dilate enough to allow blood flow to the affected areas. The pain of angina pectoris is also related to insufficient dilation of the coronary arteries . Treatment with vitamin C has consistently resulted in improved dilation of blood vessels in individuals with atherosclerosis as well as those with angina pectoris, congestive heart failure, high cholesterol, and high blood pressure. Improved blood vessel dilation has been demonstrated at a dose of 500 mg of vitamin C daily .
Vitamin C: hypertension

Individuals with high blood pressure (hypertension) are at increased risk of developing cardiovascular diseases. Several studies have demonstrated a blood pressure lowering effect of vitamin C supplementation. One recent study of individuals with high blood pressure found that a daily supplement of 500 mg of vitamin C resulted in an average drop in systolic blood pressure of 9% after 4 weeks . It should be noted that those participants who were taking antihypertensive medication continued taking it throughout the 4-week study. Because the findings regarding vitamin C and high blood pressure have not yet been replicated in larger studies it is important for individuals with significantly high blood pressure to continue current therapy (medication, lifestyle changes, etc.) in consultation with their health care provider.
Vitamin C: cancer

Studies in the 1970's and 1980's conducted by Linus Pauling and colleagues suggested that very large doses of vitamin C (10 grams/day intravenously for 10 days followed by at least 10 grams/day orally indefinitely) were helpful in increasing the survival time and improving the quality of life of terminal cancer patients . However, two randomized placebo-controlled studies conducted at the Mayo clinic found no differences in outcome between terminal cancer patients receiving 10 grams of vitamin C/day orally or placebo There were significant methodological differences between the Mayo Clinic and Pauling's studies, and recently, two researchers from the NIH suggested that the route of administration (intravenous versus oral) may have been the key to the discrepant results. Intravenous (IV) administration can result in much higher blood levels of vitamin C than oral administration, and levels that are toxic to certain types of cancer cells in culture can be achieved with intravenous but not oral administration of vitamin C . Thus, it appears reasonable to reevaluate the use of high-dose vitamin C as cancer therapy.

Currently, there are no results from controlled clinical trials indicating that vitamin C would adversely affect the survival of cancer patients. However, vitamin C should not be used in place of therapy that has been demonstrated effective in the treatment of a particular type of cancer, for example, chemotherapy or radiation therapy . If an individual with cancer chooses to take vitamin supplements, it is important that the clinician coordinating his or her treatment is aware of the type and dose of each supplement. While research is underway to determine whether combinations of antioxidant vitamins might be beneficial as an adjunct to conventional cancer therapy, definitive conclusions are not yet possible .

In a presentation at a meeting of the American Cancer Society, a scientist suggested that supplemental vitamin C might enhance the growth of cancer cells or protect them from cell-killing free radicals produced by radiation and some forms of chemotherapy. An article published in the Spring/Summer 2000 issue of the Linus Pauling Institute newsletter, Is vitamin C harmful for cancer patients? , provides additional insight on this topic.
Vitamin C: diabetes Mellitus

Cardiovascular diseases (heart disease and stroke) are the leading cause of death in individuals with diabetes . Evidence that diabetes is a condition of increased oxidative stress led to the hypothesis that higher intakes of antioxidant nutrients could help decrease cardiovascular disease risk in diabetic individuals. In support of this hypothesis, a 16-year study of 85,000 women, 2% of whom were diabetic, found that vitamin C supplement use (400 mg/day or more) was associated with significant reductions in the risk of fatal and nonfatal coronary heart disease in the entire cohort as well as those with diabetes . In contrast, a 15-year study of postmenopausal women found that diabetic women who reported taking at least 300 mg/day of vitamin C from supplements when the study began were at significantly higher risk of death from coronary heart disease and stroke than those who did not take vitamin C supplements . Vitamin C supplement use was not associated with a significant increase in cardiovascular disease mortality in the cohort as a whole. Although a number of observational studies have found that higher dietary intakes of vitamin C are associated with lower cardiovascular disease risk, randomized controlled trials have not found antioxidant supplementation that included vitamin C to reduce the risk of cardiovascular disease in diabetic or other high-risk individuals .

It is possible that genetic differences may influence the effect of vitamin C supplementation on cardiovascular disease. When the results of one randomized controlled trial were reanalyzed based on haptoglobin genotype, antioxidant therapy (1000 mg/d vitamin C + 800 IU/d vitamin E) was associated with improvement of coronary atherosclerosis in diabetic women with two copies of the haptoglobin 1 gene but worsening of coronary atherosclerosis in those with two copies of the haptoglobin 2 gene . The significance of these findings is not entirely clear, but they suggest that there may be a subpopulation of people with diabetes who will benefit from antioxidant therapy while others may not benefit or could actually be harmed. Since randomized controlled trials have not found that supplementation with vitamin C is beneficial in preventing or treating heart disease in individuals with diabetes, individuals with diabetes should avoid consuming more than 250 mg/day from vitamin C supplements until more research is available. Since vitamin C intake from foods was not associated with increased mortality from cardiovascular disease, there is no reason to limit the intake of vitamin C-rich fruits and vegetables.

Vitamin C: common cold

The work of Linus Pauling stimulated public interest in the use of large doses (greater than 1 g/day) of vitamin C to prevent the common cold . In the past 30 years, numerous placebo -controlled trials have examined the effect of vitamin C supplementation on the prevention and treatment of colds. A meta-analysis of 30 placebo-controlled prevention trials found that vitamin C supplementation in doses up to 2 g/day did not decrease the incidence of colds (40) . However, in a subgroup of marathon runners, skiers and soldiers training in the Arctic, doses ranging from 250 mg/day to 1 g/day decreased the incidence of colds by 50%. Overall, the preventive use of vitamin C supplementation reduced the duration of colds by about 8% in adults and 14% in children. Most of the prevention trials used a dose of 1 g/day. When treatment was started at the onset of symptoms, vitamin C supplementation did not shorten the duration of colds in 7 placebo-controlled trials at doses ranging from 1-4 g/day. For a more detailed discussion on vitamin C and the common cold, see the Linus Pauling Institute's Spring/Summer 2006 Research Newsletter .

Sources
Vitamin C: food Sources

As shown in the table below different fruits and vegetables vary in their vitamin C content, but five servings (2½ cups) of fruits and vegetables should average out to at least 200 mg of vitamin C. If you wish to check foods you eat frequently for their nutrient content, search the USDA food composition database .
Food Serving Vitamin C (mg)
Orange juice ¾ cup (6 ounces) 75
Grapefruit juice ¾ cup (6 ounces) 60
Orange 1 medium 70
Grapefruit ½ medium 44
Strawberries 1 cup, whole 82
Tomato 1 medium 23
Sweet red pepper ½ cup, raw chopped 141
Broccoli ½ cup, cooked 58
Potato 1 medium, baked 26
Vitamin C: supplements

Vitamin C (L-ascorbic acid) is available in many forms, but there is little scientific evidence that any one form is better absorbed or more effective than another.
Natural vs. synthetic vitamin C

Natural and synthetic L-ascorbic acid are chemically identical and there are no known differences in their biological activities or bioavailability .
Mineral ascorbates

Mineral salts of ascorbic acid are buffered and therefore, less acidic than ascorbic acid. Some people find them less irritating to the gastrointestinal tract than ascorbic acid. Sodium ascorbate and calcium ascorbate are the most common forms, although a number of other mineral ascorbates are available. Sodium ascorbate generally provides 131 mg of sodium per 1,000 mg of ascorbic acid, and pure calcium ascorbate provides 114 mg of calcium per 1,000 mg of ascorbic acid.
Vitamin C with bioflavonoids

Bioflavonoids are a class of water-soluble plant pigments that are often found in vitamin C-rich fruits and vegetables, especially citrus fruits. Although many bioflavonoids are thought to function as antioxidants, there is little evidence that the bioflavonoids in most commercial preparations increase the bioavailability or efficacy of vitamin C .
Ascorbate and vitamin C metabolites

One such supplement (Ester-C ® ) contains mainly calcium ascorbate, but also contains small amounts of the vitamin C metabolites dehydroascorbate (oxidized ascorbic acid), calcium threonate, and trace levels of xylonate and lyxonate. Although the metabolites are supposed to increase the bioavailability of vitamin C, the only published study in humans found no difference between Ester-C ® and commercially available ascorbic acid tablets with respect to the absorption and urinary excretion of vitamin C . Ester-C ® should not be confused with ascorbyl palmitate, which is also marketed as "vitamin C ester" (see below).
Vitamin C: ascorbyl palmitate

Ascorbyl palmitate is actually a vitamin C ester (vitamin C that has been esterified to a fatty acid). In this case, vitamin C is esterified to the saturated fatty acid, palmitic acid, resulting in a fat-soluble form of vitamin C. Ascorbyl palmitate has been added to a number of skin creams due to interest in its antioxidant properties as well as the important role of vitamin C in collagen synthesis . Although ascorbyl palmitate is also available as an oral supplement, it is likely that most of it is hydrolyzed (broken apart) to ascorbic acid and palmitic acid in the digestive tract before it is absorbed . Ascorbyl palmitate is also marketed as, "vitamin C ester," which should not be confused with Ester-C ® (see above).

For a more detailed review of scientific research on the bioavailability of different forms of vitamin C, see The Bioavailability of Different Forms of Vitamin C .
Vitamin C: safety
Vitamin C: toxicity

A number of possible problems with very large doses of vitamin C have been suggested, mainly based on in vitro experiments or isolated case reports , including: genetic mutations , birth defects, cancer , atherosclerosis , kidney stones , "rebound scurvy ", increased oxidative stress , excess iron absorption, vitamin B-12 deficiency, and erosion of dental enamel. However, none of these adverse health effects have been confirmed, and there is no reliable scientific evidence that large amounts of vitamin C (up to 10 grams/day in adults) are toxic or detrimental to health. With the latest RDA published in 2000, a tolerable upper intake level ( UL ) for vitamin C was set for the first time. A UL of 2 grams (2,000 milligrams) daily was recommended in order to prevent most adults from experiencing diarrhea and gastrointestinal disturbances . Such symptoms are not generally serious, especially if they resolve with temporary discontinuation or reduction of high-dose vitamin C supplementation. For a more thorough discussion of the Linus Pauling Institute's response to the UL for vitamin C, see the article, The New Recommendations for Dietary Antioxidants: A Response and Position Statement by the Linus Pauling Institute , in the Spring/Summer 2000 newsletter. A more detailed discussion of vitamin C and the risk of kidney stones can be found in the article, What About Vitamin C and Kidney Stones? , in the Fall/Winter 1999 newsletter.
Tolerable Upper Intake Level (UL) for Vitamin C
Age Group UL (mg/day)
Infants 0-12 months Not possible to establish*
Children 1-3 years 400
Children 4-8 years 650
Children 9-13 years 1,200
Adolescents 14-18 years 1,800
Adults 19 years and older 2,000

*Source of intake should be from foods or formula only.

Does vitamin C promote oxidative damage under physiological conditions? Vitamin C is known to function as a highly effective antioxidant in living organisms. However, in test tube experiments, vitamin C can interact with some free metal ions to produce potentially damaging free radicals . Although free metal ions are not generally found under physiological conditions, the idea that high doses of vitamin C might be able to promote oxidative damage in vivo has received a great deal of attention. Widespread publicity has been given to a few studies suggesting a pro-oxidant effect of vitamin C , but these studies turned out to be either flawed or of no physiological relevance. A recent comprehensive review of the literature found no credible scientific evidence that supplemental vitamin C promotes oxidative damage under physiological conditions or in humans . Studies that report a pro-oxidant effect for vitamin C should be evaluated carefully to determine whether the study system was physiologically relevant, and to rule out the possibility of methodological and design flaws.

For example, a study in the June 15, 2001, issue of the journal Science shows that lipid hydroperoxides (rancid fat molecules) can react with vitamin C to form products that could potentially harm DNA, although the reaction of these products with DNA was not demonstrated in the study . To find out why the Linus Pauling Institute considers the study's conclusions unwarranted, see Vitamin C doesn't cause cancer! in the Linus Pauling Institute Newsletter.
Vitamin C: drug Interactions

A number of drugs are known to lower vitamin C levels, requiring an increase in its intake. Estrogen-containing contraceptives (birth control pills) are known to lower vitamin C levels in plasma and white blood cells. Aspirin can lower vitamin C levels if taken frequently. For example, two aspirin tablets taken every six hours for a week has been reported to lower white blood cell vitamin C by 50%, primarily by increasing urinary excretion of vitamin C .

There is some evidence, though controversial, that vitamin C interacts with anticoagulant medications (blood thinners) such as warfarin (Coumadin). Large doses of vitamin C may block the action of warfarin, requiring an increase in dose to maintain its effectiveness. Individuals on anticoagulants should limit their vitamin C intake to 1 gram/day and have their prothrombin time monitored by the clinician following their anticoagulant therapy. Because high doses of vitamin C have also been found to interfere with the interpretation of certain laboratory tests (e.g., serum bilirubin, serum creatinine, and the guaiac assay for occult blood) it is important to inform one's health care provider of any recent supplement use .
Vitamin C: antioxidant Supplements and HMG-CoA Reductase Inhibitors (Statins)

A 3-year randomized controlled trial in 160 patients with documented coronary heart disease (CHD) and low HDL levels found that a combination of simvastatin (Zocor) and niacin increased HDL 2 levels, inhibited the progression of coronary artery stenosis (narrowing), and decreased the frequency of cardiovascular events, such as myocardial infarction (heart attack) and stroke . Surprisingly, when an antioxidant combination (1,000 mg vitamin C, 800 IU alpha-tocopherol, 100 mcg selenium, and 25 mg beta-carotene daily) was taken with the simvastatin-niacin combination, the protective effects were diminished. Since the antioxidants were taken together in this trial, the individual contribution of vitamin C cannot be determined. In contrast, a much larger randomized controlled trial of simvastatin and an antioxidant combination (600 mg vitamin E, 250 mg vitamin C, and 20 mg beta-carotene daily) in more than 20,000 men and women with coronary artery disease or diabetes found that the antioxidant combination did not diminish the cardioprotective effects of simvastatin therapy over a 5-year period . These contradictory findings indicate that further research is needed on potential interactions between antioxidant supplements and cholesterol-lowering agents, such as HMG-CoA reductase inhibitors (statins).
Vitamin C: linus Pauling Institute Recommendations

The Linus Pauling Institute recommends a vitamin C intake of at least 400 mg daily—the amount that has been found to fully saturate plasma and circulating cells with vitamin C in young, healthy nonsmokers . Consuming at least five servings (2½ cups) of fruits and vegetables daily may provide about 200 mg of vitamin C. Most multivitamin supplements provide 60 mg of vitamin C.
Vitamin C: older adults (65 years and older)

Although it is not yet known with certainty whether older adults have higher requirements for vitamin C than younger people, some older populations have been found to have vitamin C intakes considerably below the RDA of 75 and 90 mg/day for women and men, respectively. A vitamin C intake of at least 400 mg daily may be particularly important for older adults who are at higher risk for chronic diseases.

For more information on the difference between Dr Linus Pauling's recommendation and the Linus Pauling Institute's recommendation for vitamin C intake , select the highlighted text.

References

Written by:
Jane Higdon, Ph.D.
Linus Pauling Institute
Oregon State University

Reviewed by:
Balz Frei, Ph.D.
Director and Endowed Chair, Linus Pauling Institute
Professor, Dept. of Biochemistry and Biophysics
Oregon State University

Last updated 01/31/2006 Copyright 2000-2006 Linus Pauling Institute

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The Linus Pauling Institute Micronutrient Information Center provides scientific information on health aspects of micronutrients and phytochemicals for the general public. The information is made available with the understanding that the author and publisher are not providing medical, psychological, or nutritional counseling services on this site. The information should not be used in place of a consultation with a competent health care or nutrition professional.

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