Vitamin B6 status can impact mood, sleep, heart health, mental health and more. Supplementation may help improve digestion, mental health, inflammation, pain, and more. However, it comes with certain health risks. Read on to learn more about pyridoxine sources, benefits, and side effects.
What is Vitamin B6?
B6 is a versatile vitamin with a multitude of functions. Because it is involved in so many enzymatic reactions, adequate levels are key for promoting and maintaining a healthy body.
This post will delve into how B6 affects each sector of the body and the numerous benefits it offers.
“Vitamin B6” is a term that actually refers to six compounds in the body that all work in a similar way.
The first three are [1]:
- pyridoxine (PN), an alcohol
- pyridoxal (PL), an aldehyde
- pyridoxamine (PM), which contains an amino group
Their respective 5′-phosphate esters make up the remaining three [1]:
- Pyridoxal-5′-phosphate (PLP or P-5-P)
- Pyridoxine-5′-phosphate (PNP)
- Pyridoxamine 5′ phosphate (PMP)
The human body cannot make vitamin B6 in any of its forms apart from dietary intake, so it is important to include foods rich in vitamin B6 as a part of your healthy diet.
For some people, it may also be necessary to supplement with vitamin B6 (Pyridoxine HCl) or P-5-P.
Pyridoxal-5′-phosphate (PLP, P-5-P) can be found in supplement form as an alternative to taking B6 (pyridoxine). In a healthy body, the liver converts B6 to the active form, P-5-P. However, certain individuals may have difficulty making that conversion, and therefore may need to take vitamin B6 in its already active form: P-5-P.
Role in Anxiety & Sleep
Older studies reported low B6 levels in people with anxiety, but newer studies debunked them. People with depression have low B6 levels, and this might explain why supplementing with vitamin B6 reduced anxiety in people with depression in some clinical trials [2, 3].
P5P is needed for the production of melatonin, also known as the sleep hormone. Research hasn’t found a direct link between P-5-P levels and insomnia, but taking vitamin B6 before bed increased melatonin release from the pineal gland in a study of 120 children [4, 5, 6].
Vitamin B6 (Pyridoxine) Health Benefits
Effective:
1) Vitamin B6 Deficiency
Different drugs and conditions may deplete vitamin B6, triggering nerve damage and other deficiency symptoms. Supplementation can successfully treat or prevent deficiency caused by the following drugs [7, 8, 9, 10]:
- NSAIDs
- Antiepileptics (seizure medications)
- Antibiotics (penicillamine)
- Drugs for tuberculosis (isoniazid, cycloserine)
Experts suggest preventive supplementation in people with [11, 12, 13, 14, 15]:
- Digestive disorders (celiac disease and IBD)
- Malnutrition
- Alcohol dependence
- Kidney failure
2) Sideroblastic Anemia
In sideroblastic anemia, the bone marrow produces defective cells with iron rings (sideroblasts) instead of healthy red blood cells, causing a drop in hemoglobin levels. It can be acquired (due to vitamin B6 deficiency or alcoholism) or inborn [16].
Vitamin B6 is an approved treatment for this condition, but it may not always be effective. In general, acquired cases respond better [17, 18].
According to individual case reports, some patients may prefer the active form, P-5-P, but the evidence is limited [19, 20].
3) Seizures
Deficiency in the active pyridoxal phosphate (P-5-P) form of B6 in the brain can cause neurological dysfunction, particularly epilepsy [21].
The lack of vitamin B6 can cause severe neurological damage right after birth; it usually results in seizures, known as vitamin B6-dependent epilepsy. Intravenous pyridoxine is the treatment of choice and can be lifesaving [22, 23, 24].
Due to rare genetic disorders, some infants may not be able to convert vitamin B6 into P-5-P (PLP). Doctors have coined the term PLP-dependent epilepsy and reported success with the active form in such cases [25, 26, 27].
4) Morning Sickness
Due to significant symptom reduction and good safety profile, pyridoxine is one of the treatment options for morning sickness (nausea and vomiting during pregnancy) [28, 29].
Possibly Effective:
5) PMS
According to multiple clinical trials, taking a combination of B6 and magnesium supplements significantly reduces anxiety, depression, breast pain, and other symptoms of premenstrual syndrome or PMS [30, 31, 32].
6) High Homocysteine
Low B6 is associated with higher homocysteine levels, which can lead to brain damage and heart disease [33, 34].
Vitamin B6, in combination with folic acid, may reduce high homocysteine levels after meals. However, the researchers suggest a major role of folic acid in this effect [35, 36].
In general, pyridoxine appears to be effective at lowering homocysteine only in combination with folic acid and vitamin B12 in deficient patients [37, 38].
Insufficient Evidence:
No valid clinical evidence supports the use of pyridoxine supplements for any of the conditions in this section. Below is a summary of up-to-date animal studies, cell-based research, or low-quality clinical trials which should spark further investigation. However, you shouldn’t interpret them as supportive of any health benefit.
7) Histamine Intolerance
Even though B6 helps form histamine, it’s also important for normal functioning of diamine oxidase (DAO), the enzyme which breaks down histamine [39].
Intake of B6 could help lower histamine levels and benefit some histamine intolerant patients who experience headaches from histamine-rich foods and drinks [40].
More research is needed before jumping to conclusions.
8) Inflammatory Conditions
Systemic inflammation may be associated with decreased B6 status. Specifically, blood levels of P-5-P were 24% lower in individuals with the highest inflammation in one study [41].
Low levels of B6 are associated with inflammatory conditions such as inflammatory bowel disease (IBD) and cardiovascular disease in some patients [42, 43].
Patients with rheumatoid arthritis tend to have low B6, but supplementation may not relieve the symptoms [44].
On the other hand, in 2010, a Taiwanese study of rheumatoid arthritis patients found that vitamin B6 supplementation at 100 mg/day suppressed IL-6 and TNF-alpha over a 3-month period. Blood levels of IL-6 remained significantly inversely related to blood levels of P-5-P [45].
B6 inhibits pro-inflammatory NF-κB activation in mouse cells [46].
Further research should cast more light on the connection between vitamin B6 status and inflammatory conditions and the potential benefits of supplementation.
9) Cancer Prevention
A comprehensive meta-analysis of 121 observational and nine controlled trials found an inverse association between pyridoxine intake and the risk of different cancers. However, the evidence was much stronger for food B6 sources, compared with supplements [47].
While optimal pyridoxine intake plays a clear role in cancer prevention, more studies should investigate the potential benefits of supplementation.
10) Heart Disease
High intake of B6 and folate was associated with decreased chance of dying from stroke, coronary heart disease, or heart failure in nearly 60,000 Japanese individuals [48].
Dietary intake of B6 was associated with a reduced risk of coronary heart disease among middle-aged non-multivitamin supplement users [49].
Although combinations of vitamin B6, folate, and vitamin B12 may reduce homocysteine, their effects on heart disease risk are mixed and don’t allow for a definite conclusion [50, 51, 52].
Studies have yet to reveal more details and show if supplemental vitamin B6 lessens inflammation in patients with cardiovascular disease.
11) Depression
According to preliminary research, low levels of B6 may be associated with symptoms of depression [53].
Still, B6 was not an effective treatment for depression in a two-year study with older men [54].
Some women who take in more foods that contain B6 have lower chances of getting depression [55].
Women who have post-pregnancy depression don’t show signs of B6 deficiency [56].
Further studies should investigate the conflicting evidence for the role of pyridoxine status in depression.
12) Pain
B6 supplements may reduce breast pain (cyclic mastalgia) [57].
Migraines have been linked to B6 deficiency in some patients [58].
There’s not enough clinical evidence to support the painkiller effects of pyridoxine.
13) Diabetes
B6 deficiency is common among type 2 diabetes patients [59].
Pyridoxine supplementation may help with gestational diabetes as it increases glucose tolerance [60, 61].
However, these findings stem from two small trials that lacked control groups. More research is needed to investigate the role of vitamin B6 in blood sugar control.
Possibly Ineffective:
1) Osteoporosis
B6 deficiency leads to reduced neutrophils and lymphocytes resulting in bone marrow deficiency (in rats) [62].
According to two studies of 200 participants, pyridoxine deficiency may be associated with higher rates of hip fractures and lower bone mineral density [63, 64].
However, a much larger trial of 8,164 stroke survivors found no significant benefits of pyridoxine on osteoporosis risk. B6 supplementation was associated with a slightly increased risk of hip fractures in a meta-analysis of two large studies [65, 66].
Although adequate pyridoxine intake is important for bone health, supplementation doesn’t appear to reduce the risk of osteoporosis and may even be counterproductive.
Vitamin B6 Intake & Supplements
Daily Requirements
| 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 |
Food Sources
Some Dietary Sources of Vitamin B6 [67]:
- Beef liver: 0.9 mg per 3 oz serving
- Sockeye salmon: 0.6 mg per 3 oz serving
- Chicken breast: 0.5 mg per 3 oz serving
- Turkey (meat only): 0.4 mg per 3 oz serving
- Ground beef 86% lean: 0.3 mg per 3 oz serving
Deficiency
The following drugs may deplete vitamin B6 and increase the risk of deficiency [7, 8, 9, 10]:
- NSAIDs
- Antiepileptics (seizure medications)
- Antibiotics (penicillamine)
- Drugs for tuberculosis (isoniazid, cycloserine)
Conditions that increase the risk of deficiency include [11, 12, 13, 14, 15]:
- Digestive disorders (celiac disease and IBD)
- Malnutrition
- Alcohol dependence
- Kidney failure
Vitamin B6 Side Effects and Safety
This list does not cover all possible side effects. Contact your doctor or pharmacist if you notice any other side effects. In the US, you may report side effects to the FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch. In Canada, you may report side effects to Health Canada at 1-866-234-2345.
High intakes of vitamin B6 from food sources have not been reported to cause adverse effects. Supplements are also safe and well tolerated in adequate doses [68].
However, taking 1 – 6 grams of B6 per day for more than a year can lead to severe neuropathy with loss of movement control [68].
The tolerable upper intake level set for adults is 100 mg per day [69].
Fortunately, symptoms usually go away after supplementation has been stopped. Other symptoms of excessive vitamin B6 supplementation include painful skin lesions, light sensitivity, and symptoms of digestive upset, such as nausea and heartburn [68].
Drug Interactions
Supplement-drug interactions can be dangerous and, in rare cases, even life-threatening. Always consult your doctor before supplementing and let him know about all drugs and supplements you are using or considering.
Here are some medications that interfere with the metabolism of vitamin B6 or that are affected by B6 supplementation:
Broad-spectrum antibiotic Cycloserine (Seromycin®), used to treat tuberculosis, increases urinary loss of B6. This may worsen the seizures and neurotoxicity associated with cycloserine. (B6 supplements can help prevent these adverse effects) [68].
Antiepileptic Medications, including valproic acid (Depakene®, Stavzor®), carbamazepine (Carbatrol®, Epitol®, Tegretol®, and others), and phenytoin (Dilantin®) increase the breakdown rate of vitamin B6, resulting in low blood levels of P5P and high homocysteine. High homocysteine levels in antiepileptic drug users may increase the rate of seizures and stroke [68].
Anti-seizure medications phenytoin and phenobarbital may be reduced in the blood by B6 supplementation of 200 mg/day for 12 – 120 days [68].
COPD medications like Theophylline (Aquaphyllin®, Elixophyllin®, Theolair®, Truxophyllin®, et cetera) can cause low blood levels of P5P, which could cause seizures [68].
Non-steroidal Anti-inflammatory Drugs (NSAIDS) can lower blood levels of B6 (P5P), especially when taken chronically, over 6 months’ time [70].
