Vitamin B6

Vitamin B6, scientifically known as pyridoxine, is a vital water-soluble nutrient essential for numerous physiological processes. 

Its multifaceted role encompasses crucial functions such as neurotransmitter synthesis, facilitating communication between brain and nerve cells, and ensuring the smooth breakdown of fats and proteins. 

Additionally, vitamin B6 plays a pivotal role in red blood cell formation and the conversion of dietary nutrients into usable energy for cellular functions. It is integral in regulating homocysteine levels in the blood, contributing significantly to cardiovascular health. 

Since the human body cannot synthesize vitamin B6 independently, obtaining an adequate supply through dietary sources or supplementation is imperative for maintaining overall health and well-being.

Overview of B Vitamin Family

The B vitamin family comprises a group of water-soluble vitamins that play critical roles in numerous physiological processes essential for human health. 

Comprising eight distinct vitamins, it includes riboflavin (B2), niacin (B3), pantothenic acid (B5), pyridoxine (B6), biotin (B7), folate (B9), and cobalamin (B12), these vitamins are intricately related and often function as coenzymes in various metabolic pathways. 

VItamin B12 is the only B vitamin that can be stored in the body, in the liver.  All other B vitamins are quickly excreted through the urine, therefore they require daily repletion.  

Individually, the B vitamins contribute to energy production, DNA synthesis, nervous system function, and red blood cell formation, among other vital functions. Collectively, the B vitamins are indispensable for maintaining overall health and well-being, underscoring their importance in supporting various physiological systems within the human body.

Pyridoxine (Vitamin B6)

What is Pyridoxine? 

Pyridoxine, or vitamin B6, is a water soluble B vitamin with essential functions in human health and wellness.  

In mammals, there are six naturally occurring active compounds of vitamin B6.  The most prevalent of these include pyridoxine, pyridoxal, and pyridoxamine. 

The active coenzyme forms are a group of vitamers that include pyridoxine 5’phosphate (PNP), pyridoxal 5'phosphate (PLP) and pyridoxamine 5'phosphate (PMP).  P5P typically refers to the pyridoxal form, particularly when supplemented.  

This phosphorylated form is then converted to 4-pyridoxic acid and excreted in urine by the kidneys.  

PLP and PMP predominate in animal tissues, while PNP predominates in plants.  [10.]

Upon ingestion, vitamin B6 enters the liver where it is converted to the active form P5P.  

P5P serves as a coenzyme involved in numerous biochemical reactions throughout the body, including amino acid metabolism, neurotransmitter synthesis, and the breakdown of glycogen and fatty acids for energy production. 

Additionally, P5P plays a crucial role in the synthesis of hemoglobin and the regulation of homocysteine levels, thereby contributing to cardiovascular health. 

Functions of Pyridoxine: What Does Pyridoxine Do in the Body?

Vitamin B6 exerts a wide range of beneficial effects on human health.  

• Acts as a coenzyme for more than 100 enzymes involved in amino acid metabolism, including aminotransferases, decarboxylases, racemases, and dehydratases.

• Functions as a coenzyme for δ-aminolevulinate synthase, initiating heme biosynthesis.  [10.]

• Serves as a coenzyme for cystathionine β-synthase and cystathioninase, crucial enzymes in the transsulfuration pathway from homocysteine to cysteine.  [10., 11.]

• Plays a pivotal role in neurotransmitter synthesis, including serotonin, dopamine, norepinephrine, and gamma-aminobutyric acid (GABA), essential for proper brain function and mood regulation.  [10.]

• Influences cognitive development due to its involvement in neurotransmitter synthesis.

• Participates in glycogenolysis and gluconeogenesis, critical processes for energy metabolism.  [4.]

• Essential for proper immune function, including decreased production of lymphocytes and antibodies.  [4.] 

• Plays a role in steroid hormone metabolism and regulation by influencing steroid hormone receptor transcription.  [3.]

• Involved in gene expression and regulation through its role in coenzyme forms of enzymes influencing DNA synthesis and repair.  [3.]

Recommended Daily Allowance (RDA) of Pyridoxine

The RDA for adult men and women up to age 50 is 1.3 mg/day.  Beyond age 50, the RDA for men is 1.7 mg/day and 1.5 mg/day for women.  In pregnancy the RDA increases to 1.9 mg/day, and it is set at 2 mg/day in lactation.  [10.]  

Sources of Pyridoxine  [16.]

Fish, beef liver, organ meats, potatoes, starchy vegetables, and noncitrus fruits are rich sources of vitamin B6. In the United States, adults primarily obtain dietary vitamin B6 from fortified cereals, beef, poultry, starchy vegetables, and select noncitrus fruits. 

Approximately 75% of vitamin B6 from a mixed diet is bioavailable.

Animal Sources of Vitamin B6:

• Beef liver and other organ meats
• Fish: tuna, salmon
• Poultry: chicken, turkey
• Beef
• Dairy products

Plant Sources of Vitamin B6:

• Chickpeas
• Fortified breakfast cereals
• Potatoes
• Banana
• Tomatoes 
• Bulgur
• Squash, winter

Pyridoxine Forms and Supplementation Indications

Pyridoxine Supplement Forms

Pyridoxine is available as a single-vitamin supplement, or as part of a B vitamin complex.  Additionally, it is available as pyridoxine and as the active form, P5P.  

Indications for Pyridoxine Supplementation  [5.]

Vitamin B6 Deficiency

Vitamin B6 supplementation is indicated for the treatment of vitamin B6 deficiency, which can occur due to inadequate dietary intake, malabsorption disorders, or certain medications.  It is commonly used to treat sideroblastic anemia, a side effect of vitamin B6 deficiency.

Increased Need for Vitamin B6

Supplementation may be recommended for individuals with conditions that increase the need for vitamin B6, such as pregnancy, breastfeeding, certain medical conditions like kidney disease, and certain medications that interfere with vitamin B6 metabolism.

Neurological Symptoms

It is used to manage conditions associated with low levels of vitamin B6, such as certain types of seizures and certain neurologic disorders like peripheral neuropathy.

Vitamin B6 may also be helpful in treating mood disorders including anxiety and depression.  [7.]

Premenstrual Symptoms

Vitamin B6 supplementation may also be beneficial in managing premenstrual syndrome (PMS) symptoms, including mood swings, irritability, and breast tenderness.

Cardiovascular Disease

Additionally, vitamin B6 supplementation has been studied for its potential role in reducing the risk of cardiovascular disease, although more research is needed to establish definitive recommendations in this area.  

Vitamin B6 is well-known for its ability to reduce homocysteine levels, which are associated with cardiovascular disease.  [10.]

Testing Options for Pyridoxine Levels  [10.]

Blood Tests

Blood tests are commonly used to measure pyridoxine levels in the body. These tests typically involve drawing a blood sample from a vein, which is then analyzed in a laboratory to determine the concentration of pyridoxine present. 

This test may assess levels of pyridoxine in whole blood, serum, plasma or red blood cells.  Plasma PLP concentration is often considered the best single indicator of B6 status, as it reflects tissue stores and changes relatively slowly in response to vitamin intake, taking about 10 days to reach a new steady state.  [10.]

Serum/Plasma Testing

Blood testing for vitamin B6 status involves measuring concentrations of vitamin B6 and its active forms in the blood, including plasma pyridoxal 5'-phosphate (PLP) and total blood vitamin concentrations.

Total blood vitamin concentrations including various B6 vitamers can also be measured, but their usefulness as status indicators is limited due to considerable fluctuations.

Erythrocytes

Erythrocyte concentrations correlate strongly with whole-blood levels but not with urinary excretion. While theoretically more reflective of status, no clear advantage over whole-blood levels is evident, likely due to factors like absorption variability and tissue utilization discrepancies.

Urine Tests

Urinary testing for vitamin B6 involves measuring excretion of B6 metabolites, particularly 4-pyridoxic acid (4-PA), which responds almost immediately to changes in dietary B6 intake.

While urinary excretion of B6 metabolites reflects recent intake, it is of limited value in assessing overall status, as it does not provide information on tissue stores.

A suggested cutoff value of greater than 3 μmol/day for 4-PA excretion is indicative of adequate status, but its use presupposes an adequate B6 intake of about 1 mg/day, leading to limitations in assessing deficiency.

Test Procedure and Preparation Guidelines

The procedure for testing pyridoxine levels typically involves a blood draw.  Alternatively, urine samples may be collected at home or in a lab setting.  

Before undergoing pyridoxine testing, individuals may be instructed to fast for a certain period and avoid consuming pyridoxine-rich foods or supplements to prevent interference with the results.

It's essential to follow any preparation guidelines provided by the healthcare team to ensure accurate test results and to discuss any medications or supplements being taken that could affect pyridoxine levels.

Interpretation of Pyridoxine Testing

While individual labs may report different reference ranges, the reference ranges for pyridoxine testing from one lab are:  [1.]

Plasma: 3.4 – 65.2 µg/L, although adequacy is reported as any level above 5.1 µg/L.  

Whole Blood/Erythrocyte: contact lab for reference ranges used.

Urine: contact lab for reference ranges used.

Clinical Significance of High Pantothenic Acid Levels [10.]

High pyridoxine levels, while uncommon, can have clinical significance and may lead to adverse effects. No reports of excessive pyridoxine levels due to food intake are available; adverse effects of vitamin B6 intake are associated with excessive supplementation.  

Excessive pyridoxine supplementation, particularly in large oral doses used to manage conditions like carpal tunnel syndrome and premenstrual syndrome, has been associated with adverse effects, notably sensory neuropathy and dermatological lesions. 

Sensory neuropathy, characterized by severe nerve damage in the extremities, has been reported in individuals taking high doses of pyridoxine for extended periods. 

Dermatological lesions, though less common, have also been observed with prolonged high-dose pyridoxine intake. 

While lower doses appear to carry a reduced risk of neuropathy, the exact threshold for adverse effects remains uncertain. Additionally, there have been isolated reports linking maternal pyridoxine supplementation during pregnancy to congenital defects and B6 dependency in newborns, although controlled studies in humans have not confirmed these findings. 

Furthermore, high doses of pyridoxine have been utilized to suppress lactation post-delivery, but evidence regarding its efficacy is inconclusive, particularly at lower oral doses.

Clinical Significance of Low Pyridoxine Levels  [2.]

Low pyridoxine levels can have significant clinical implications, particularly in cases of deficiency attributed to factors such as poor renal function, autoimmune diseases, alcohol abuse, or certain medications like isoniazid, valproic acid, and phenytoin therapy. 

Clinical manifestations of vitamin B6 deficiency encompass a range of symptoms, including seborrheic dermatitis, microcytic anemia, glossitis, epileptiform convulsions, peripheral neuropathy, depression, and weakened immune function. 

Rare inborn errors of metabolism, termed vitamin B6 dependency syndromes, necessitate high doses of pyridoxine to maintain enzyme function. These syndromes encompass conditions like convulsions of the newborn and homocystinuria. 

Pyridoxine is also utilized in toxicological contexts, such as isoniazid overdose and mushroom poisoning. 

Despite conflicting evidence, pyridoxine is often used empirically to address various conditions like atopic dermatitis, alcohol intoxication, and certain psychological disorders, highlighting its diverse clinical applications.

Natural Ways to Optimize B Vitamin Status

Dietary Sources of B Vitamins

Incorporate a variety of foods rich in B vitamins such as:

• Whole grains like brown rice, oats, quinoa, and barley
• Leafy greens such as spinach, kale, and Swiss chard
• Legumes including lentils, chickpeas, and black beans
• Nuts and seeds like almonds, sunflower seeds, and flaxseeds
• Lean meats such as chicken, turkey, and beef
• Dairy products like milk, yogurt, and cheese
• Eggs, particularly the yolk which contains B vitamins
• Seafood such as salmon, tuna, and mackerel which are rich in B12
• Include fortified foods like fortified cereals, bread, and plant-based milk alternatives to increase B vitamin intake.

Lifestyle Strategies to Optimize B Vitamin Status

• Consume a balanced diet rich in fruits, vegetables, whole grains, and lean proteins to ensure adequate B vitamin intake.
• Avoid excessive alcohol consumption as it can interfere with the absorption and utilization of B vitamins, particularly B1 (thiamine), folate and vitamin B6.  [9.] 
• Manage stress levels through relaxation techniques such as deep breathing exercises, meditation, yoga, or mindfulness practices, as chronic stress can deplete B vitamin stores.  [22.] 
• Get regular physical activity, which can help improve overall metabolism and enhance the body's utilization of B vitamins.  Increasing exercise increases vitamin B needs, so supplementing may be desirable in some individuals.  [13.] 

Medications That Lower Vitamin B Levels in the Body

Individuals taking the following medications may want to discuss their B vitamin needs with their healthcare provider:

• Metformin: Used to treat type 2 diabetes, metformin can reduce vitamin B12 absorption and increase the risk of deficiency over time.  [12., 14.]
• Proton pump inhibitors (PPIs): These medications, such as omeprazole and esomeprazole, are commonly used to treat acid reflux and peptic ulcers. Long-term use of PPIs can interfere with the absorption of vitamin B12.  [8., 14.]
• Histamine H2-receptor antagonists: Drugs like ranitidine and cimetidine, used to reduce stomach acid production, may also impair vitamin B12 absorption.  [14.]
• Anticonvulsants: Some antiepileptic drugs like phenytoin, phenobarbital, and primidone can lower levels of folate and vitamin B12 in the body.  [18.] 
• Chemotherapy drugs: Chemotherapy medications can affect the body's ability to absorb and utilize B vitamins, leading to deficiencies.  [6.] 
• Oral contraceptives: Some birth control pills can deplete levels of B vitamins, particularly folate and vitamin B6.  [21.] 
• Diuretics: Certain diuretic medications, including loop and thiazide diuretics, can increase urinary excretion of B vitamins, particularly vitamin B1 (thiamine) and folate.  [15., 20.]

It's important to consult with a healthcare professional if you're taking any of these medications to discuss potential nutrient deficiencies and appropriate supplementation, if needed.

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