Vitamin B6: Benefits, Side-Effects, Dosage and Research

The B vitamins are essential in different metabolic processes vital for brain and nervous system function. These vitamins are integral in maintaining an appropriate balance between excitation and inhibition of the neurons.

One of these vitamins includes pyridoxine or vitamin B6. This vitamin is water-soluble and is found naturally in many foods and supplements. To measure the blood levels of vitamin B6, healthcare practitioners examine the level of active Pyridoxal 5′ phosphate (PLP). The PLPs act as coenzymes to more than 100 enzymes that perform different functions, from the breakdown of fats, carbohydrates and proteins.

PLPs also assist enzymes in maintaining normal levels of homocysteine, an enzyme that, when present in high levels, can lead to heart problems. PLPs also help enzymes involved in supporting brain health and immune function.

Apart from PLPs, other active forms of vitamin B6 include the following:

Pyridoxine, which is an alcohol
Pyridoxal, an aldehyde
Pyridoxamine 5′ phosphate (PMP), a coenzyme
Pyridoxamine, which contains an amino acid group
Pyridoxamine and their respective 5’-phosphate esters

What are the benefits of vitamin B6?

When present as a supplement, vitamin B6 is often prescribed for pregnant women to counter nausea due to pregnancy. However, the intake of vitamin B6 among pregnant women should be supervised by a doctor.

Sufficient levels of vitamin B6 in the body have been associated with improvements in specific healthcare conditions. Here are some benefits derived from taking vitamin B6:

Lowers cardiovascular disease risk

It is believed that vitamin B6 can reduce the risk of cardiovascular disease by lowering levels of homocysteine in the body [1]. However, determining the exact effects of vitamin B6 in lowering the risk of cardiovascular diseases is difficult. Most clinical trials include a combination of vitamin B6, folic acid and vitamin B12 when determining if B vitamins can reduce the risk of heart disease [2].

For example, the HOPE 2 trial (Heart Outcomes Prevention Evaluation 2) included supplementation of vitamin B12 at 1mg/day, folic acid at 2.5 mg/day and vitamin B6 at 50 mg/day for five years. A total of 5,500 adults were recruited. All these participants did not have any heart diseases at the start of the clinical trial. Results of this trial revealed that supplementation with the three B vitamins lowered the risk of stroke by 25% in the experimental group compared with the control group. Further, the vitamins also reduced levels of homocysteine. However, the study did not have separate results for vitamin B6 alone.

Although the HOPE 2 trial showed positive effects of B vitamins against cardiovascular events, another study [3] showed that supplementation with B vitamins only lowered homocysteine levels but did not reduce the risk of cardiovascular events. This study enrolled 5,442 women with three or more coronary risk factors or a history of heart disease. These women were treated with B vitamins supplements for 7.3 years.

Research studies have shown that there is still little evidence supporting the effectiveness of vitamin B6 alone or combined with folic acid and vitamin B12 in reducing the risk of cardiovascular events and their severity.

Premenstrual syndrome

A meta-analysis [4] of nine published trials that recruited 940 patients experiencing premenstrual syndrome suggested that taking 100 mg/day of vitamin B6 relieves premenstrual depression and syndromes. However, the clinical trials included in the meta-analysis were of low quality. This means that the findings were less conclusive than other meta-analyses, including high-quality clinical trials.

Improves cognition

Older adults may experience cognitive decline as they age. However, a study of 70 male subjects [5] aged 54 to 81 demonstrated that higher concentrations of vitamin B6 were linked to better performance on two memory tests. In contrast, the study found that higher homocysteine concentrations and lower folate and vitamin B12 were associated with poorer spatial copying skills.

The actual cause of why high levels of homocysteine are linked to poorer cognitive functioning in older adults is not fully understood yet. However, results suggest that taking the recommended dosage of vitamin B6 daily could improve cognitive functioning as one age.

However, more evidence is still needed to determine if vitamin B6 supplementation could improve cognitive function in older adults in the long term. To date, there is still conflicting evidence on the effects of vitamin B6 on cognitive function. Although the study that recruited 70 male subjects showed improvements in cognition, this is different in systematic reviews.

For example, a systematic review [6] that investigated 14 clinical trials reported that a combination of vitamin B6 with vitamin B12 and folate did not significantly improve cognitive functioning amongst those impaired or normal cognitive functioning. According to the authors of this review, the studies included in the analysis needed to be of better quality and had limited generalisability and applicability.

Reduces risk of cancer

Population-based studies have indicated an inverse relationship between vitamin B6 supplementation and cancer [7]. Deficiency in vitamin B6 has been shown to impact cancer and the stability of the genes. It has been shown that vitamin B6, along with other B vitamins, can help reduce the risk of DNA damage, which is one of the precursors of DNA mutations and cancer.

A meta-analysis [8] that reviewed nine studies demonstrated that low levels of vitamin B6 or PLP in the blood are associated with an increased risk of colorectal cancer. The same meta-analysis showed that those with high levels of vitamin B6 in their blood but still within the recommended level had a 20% reduced risk of colorectal cancer compared with those with deficient levels of vitamin B6.

Despite the studies showing a relationship between vitamin B6 and cancer risk, these studies showed that vitamin B6 did not appear to reduce the impact of cancer on the mortality of the patients or prevent cancer from occurring. Hence, more studies are still needed to determine the effects of long-term intake of vitamin B6 on the cancer risk of patients.

Pregnancy-induced nausea and vomiting

At least half of pregnant women experience vomiting, while as high as 80% of these women experience vomiting and nausea. A condition called morning sickness, vomiting may last the whole day. Although nausea and vomiting during pregnancy are not life-threatening, they can disrupt normal daily activities, physical functioning and social activities.

International and national organizations, such as the American Congress of Obstetrics and Gynecology (ACOG), recommend taking 10-25 mg of vitamin B6 three to four times daily to treat morning sickness [9]. However, the Royal College of Obstetrics and Gynaecology (RCOG) in the UK does not recommend vitamin B6 to treat morning sickness.

The evidence on the effectiveness of vitamin B6 supplementation in treating morning sickness is mixed. For example, a randomized controlled trial [10] reported that a daily intake of 30-75 mg of vitamin B6 reduces symptoms of nausea and vomiting during pregnancy. However, an extensive, systematic review [11] reported otherwise. The study found that findings remained inconclusive and vitamin B6 could not be significantly linked to the reduction of symptoms of morning sickness in pregnant women.

Vitamin B6 and diabetes

Type 2 diabetes mellitus is a condition that affects millions of people worldwide. This condition is marked by hyperglycemia or very high blood glucose levels. It is due to decreased production of insulin from the beta cells in the pancreas and reduced insulin uptake in the body’s muscles and tissues.

Some studies have linked low levels of vitamin B6 to complications of diabetes, such as retinopathy and neuropathy, in both type 1 and type 2 diabetes patients [12]. These studies also suggest that supplementation with vitamin B6 significantly reduced the progression of both neuropathy and retinopathy.

In a cohort of Japanese patients with type 2 diabetes mellitus [13], a high intake of vitamin B6 was associated with a lower incidence of complications from diabetes, such as retinopathy. The protective effects of vitamin B6 in preventing or reducing the progression of diabetes complications are also seen in animal model studies.

It is hypothesized that the protective effects of vitamin B6 against diabetes complications may be due to the antioxidant property of this vitamin. In rat model studies, the presence of vitamin B6 substantially reduced the biomarkers linked to oxidative stress.

It is widely established that oxidative stress is a significant risk factor in type 2 diabetes onset and progression. Obesity and unhealthy eating habits – common risk factors of diabetes – contribute to the development of an oxidative environment. This type of environment impairs glucose tolerance and increases insulin resistance. In turn, hyperglycemia contributes to the maintenance and progression of an oxidative environment. Consequently, diabetes has been associated with reduced levels of antioxidants and reduced efficiency in repairing damaged DNA.

Evidence from the literature has suggested that type 2 diabetes mellitus is due to DNA strand breaks and oxidative damage. Considering that vitamin B6 is a cofactor for enzymes used in the metabolism of DNA as an antioxidant molecule, it is expected that low levels of this vitamin can result in increased DNA damage due to diabetes.

Side-effects of vitamin B6

Like other micronutrients, eating fruits and vegetables rich in vitamin six does not lead to adverse effects or events. Hence, a high intake of vitamin B6 from natural food sources does not appear to have any negative effects. This is because vitamin B6 in these foods is available as the precursor of the vitamin, which is then converted to biologically active vitamin B6 molecules. Conversion to active metabolites is controlled.

However, evidence from the literature [14] has shown that chronic intake of high levels of vitamin B6, higher than the recommended dosage, leads to severe and progressive sensory neuropathy accompanied by ataxia or loss of control of bodily movements.

The severity of the symptoms of ataxia or sensory neuropathy depends on the excessive dose taken by the individuals. Symptoms often disappear when a person stops taking pyridoxine or vitamin B6 supplementation.

Apart from neurologic symptoms, here are additional symptoms of vitamin B6 overdose or excessive vitamin B6 intake:

Photosensitivity
Disfiguring dermatological lesions
Gastrointestinal symptoms, including heartburn and nausea

There are also isolated case reports [15] where pregnant women who took vitamin B6 supplementation during the first half of their pregnancy resulted in congenital disabilities in their infants. However, these cases appear to be isolated as a prospective study [16] reported that higher than standard doses of vitamin B6 taken for nine weeks (+/- 4.2 weeks) starting at seven weeks gestation did not result in any congenital abnormalities of their infants or any teratogenic effects for their infants.

Interactions of vitamin B6 with other medications

Vitamin B6 may be taken along with other medications to counter the side effects of these medications. Here are some examples of drugs that interact with vitamin B6:

Theophylline

Theophylline is a medication used to treat shortness of breath in patients with chronic bronchitis, emphysema, asthma and other lung diseases. Theophylline’s side effects include nervous and neurological symptoms, including epilepsy. Individuals treated with theophylline often have low levels of vitamin B6, which might exacerbate the side effects of theophylline. Supplementation with vitamin B6 might reduce the side effects of theophylline.

Antiepileptic medications

The breakdown of vitamin B6 is increased when an individual takes certain antiepileptic drugs, such as valproic acid. This increased catabolism or breakdown results in hyperhomocysteinemia and low plasma concentrations of vitamin B6. High levels of homocysteine could increase the risk of seizures in patients with epilepsy.

Supplementation with vitamin B6 could reduce the serum levels of antiepileptic medications, which could mean that these medications are metabolized faster when taken together with vitamin B6.

Side effects of antiepileptic medications can include depression, irritability and agitation. Evidence from the literature [17, 18] suggests that supplementing vitamin B6 at 50-350 mg/day for children and 50-100 mg/day for adults could reduce these side effects.

Food sources of vitamin B6

Vitamin B6 can be sourced from a wide variety of foods. These include fruits and vegetables. Here are some selected food sources of vitamin B6:

Meat such as ground beef, turkey, chicken breast, yellowfin tuna and beef liver
Chickpeas, boiled potatoes, fortified breakfast cereals, Spaghetti sauce, banana
Squash, rice, onions, raisins, spinach, watermelon
Cottage cheese, tofu

Dietary supplements

Vitamin B7 is available in supplements such as multivitamins. It is also a standalone supplement available in tablets or oral capsules.

Absorption of vitamin B6 is in the small intestine, similar to other vitamins and micronutrients in the body. Most of the excess vitamin B6 taken in the body is excreted in the urine.

A deficiency in vitamin B6 results in the following:

Dermatitis with cheilosis or cracks in the corners of the mouth and scaling of the lips
Electroencephalographic abnormalities
Depression
Swollen tongue
Microcytic anaemia
Weakened immune system
Confusion

In infants, vitamin B6 deficiency symptoms include the following:

Abnormally acute hearing
Irritability
Convulsive seizures

Some groups are at risk of vitamin B6 deficiency. These include:

Individuals with autoimmune disorders
Those with impaired renal function
People with alcohol dependence

Recommended Dosage

Recommended Dietary Allowance (RDA) for women 14-18 years old is 1.2 mg/day. This increases to 1.3 mg/day for women 19-50. Those who are 51 and older would require 1.5 mg/day of vitamin B6. The amount increases to 1.9 mg and 2.0 mg during pregnancy and lactation.

For men, the RDA is 1.3 mg for those aged 14-50 years old. At 51 and older, the RDA is 1.7 mg/day.

The Tolerable Upper Intake Level (UL) is an individual’s maximum daily dose without causing adverse side effects.

In adults (19 years old and older), the UL is 100 mg/day. The amount is slightly lower for teenagers and children. However, this amount could only be reached when taking multiple vitamin supplements in one day.

Toxicity

Toxicity from vitamin B6 is rare since vitamin B6 from food sources do not have a dietary limit. High doses of vitamin B6 from supplements may be tolerated as excess vitamin B6, a water-soluble vitamin is excreted in the urine.

However, toxicity can occur from the long-term use of high doses of vitamin B6. Toxicity is reached when you take at least 1000 mg of the vitamin daily for prolonged periods. Symptoms disappear after you stop taking high doses of vitamin B6. Symptoms of toxicity are as follows:

Ataxia
Nausea
Neuropathy

Latest research studies

The latest studies on vitamin B6 have been conducted. Notably its association with anxiety and depression. It is believed that vitamin B6 can help lower stress and depression.

Anxiety and depression are common mental health conditions that can adversely affect one’s thoughts, mood and physical functioning. Mood disorders and anxiety are recognized as the most pressing healthcare problems worldwide. About 14% of the world’s population experience depression at one point in their lives. In the US and the UK, it is observed that one in four people will experience depression or mood disorders at some point in their lives.

Both depression and anxiety are treated with medications such as diazepam and talking therapy, cognitive behavioural therapy and dialectical behavioural therapy. Recently, it was discovered that high doses of vitamin B6 might be effective in reducing depression and anxiety.

A study published in 2022 [19] in Human Psychopharmacology: Clinical and Experimental reported that a month-long intake of high vitamin B6 results in self-reported lower anxiety levels. The University of Reading researchers who completed the study recruited 478 young adults with self-reported anxiety or depression. The investigators randomly assigned the participants to two experimental and control groups. Participants received 100 mg/day of vitamin B6 in the first experimental group, while in the second experimental group, the young adults received 100 micrograms/day of vitamin B12. The control group only received a placebo. All participants took their supplements for 30-35 days.

The investigators wanted to examine how vitamin B6 influences Gamma-aminobutyric acid (GABA) use and uptake. It has been shown that vitamin B6 (pyridoxine) modulates the production of GABA and serotonin. GABA is described as an inhibitory neurotransmitter and messenger present in the brain. GABA helps calm the nervous system by slowing down brain activity and blocking certain impulses in the brain’s nerve cells. In turn, this blocking activity has a calming effect that can relieve fear, anxiety and stress.

Compared with the placebo group, the B12 group also has minor improvements in depression and anxiety. However, those in the vitamin B6 group exhibited the most pronounced significant effects of vitamin B6 on depression and anxiety. Further, the differences in self-reported anxiety and depression scores in the B6 group were statistically significant compared with the placebo or the B12 group.

Further, the researchers of the study found that the GABA levels in the B6 group were significantly higher compared with the B12 group or the placebo group. This was confirmed in the differences in the scores on the Screen for Adult Anxiety-Related Disorders (SCAARED) and Mood and Feelings Questionnaire (MFQ) of the participants before and after the trial.

Earlier studies have shown that people who are depressed or anxious tend to have lower levels of vitamin B6. Meanwhile, other studies have shown that combining magnesium and vitamin B6 supplementation resulted in increased physical activities and reduced depression and anxiety in individuals with low magnesium and depression.

Considering the study’s results mentioned above, vitamin B6 can actively relieve symptoms of depression and anxiety. Hence, it is crucial to add this supplement for people at risk of depression and anxiety. It is noteworthy that current medications for depression have serious side effects such as memory impairment, rebound anxiety and dependence. In contrast, vitamin B6 toxicity only occurs in very high doses. There are also no reported side effects of this micronutrient when taken within its RDA.

It is important to note that studies on vitamin B6 supplementation and depression and anxiety are still few and in their early stages. Compared with current medications for depression, vitamin B6 supplementation still has few studies to support its use for depression. Despite these observations, many people opt to undergo nutrition-based interventions due to their fewer adverse side effects than drugs.

To make vitamin B6 a viable option for treating depression and anxiety, more research studies are still needed to support the effectiveness of this micronutrient in treating depression. Further, studies that would identify other nutrition-based interventions that could improve mental health and well-being are still required. In the future, more nutrition-based interventions might be discovered and used with vitamin B6 to produce better results.

Using vitamin B6 supplementation and other therapies, such as cognitive behavioural therapy or talking therapy, may effectively address depression and anxiety in the future.

Take-home message

Vitamin B6 is a micronutrient that can be readily sourced from our food. These food sources range from meats to vegetables, suggesting that vitamin B6 can be abundantly found in the food we commonly eat. Further, many bowls of cereal are fortified with vitamin B6, which makes this micronutrient readily accessible.

Apart from food sources, vitamin B6 supplements are available and can be taken under the supervision of a medical professional.

The health benefits of vitamin B6 are well established and have been shown to improve physical and mental health. Recently, this micronutrient has been suggested to relieve symptoms of depression and stress when taken in high doses for at least a month. Hence, taking this micronutrient might be a cost-effective nutrition-based therapy without the adverse effects commonly seen in medications.

When taking this medication, always consult your doctor, especially when you are pregnant or planning to be pregnant. Doses should be tailored to your current needs to optimize their health benefits.

Further, taking this micronutrient is associated with longevity since it promotes better mental health and physical functioning. Both physical and psychological health are needed for a longer lifespan and healthy ageing.

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