Evidence: High Potential Benefits: High Safety: High
TABLE OF CONTENTS
What is pyridoxal phosphate?
Pyridoxal phosphate (also known as (Pyridoxal 5′-Phosphate, PLP, and P5P) is the bioactive form of vitamin B6. Pyridoxal phosphate is a preferred form because, unlike pyridoxine HCl, almost everyone absorbs PL5P well as it does not need to go through any conversion to become bioavailable. If you already get enough vitamin B6 from food, you should not need to take the supplement. However, it can still improve some aspects of your health beyond the baseline. This article is about the main benefits of pyridoxal phosphate, its potential side effects, the best time to take it, and more.
Potential benefits
It is important to note that all of the potential benefits mentioned below are dose-dependent. Generally, the higher the dose, the more pronounced the effects are. However, they do reach a plateau at a certain point. We will discuss the best dosing protocol later in this article.
Major benefits
Correcting a vitamin B6 deficiency – vitamin B6 deficiency can be terrible for your health and overall quality of life. Fortunately, a severe deficit is relatively rare. A mild deficiency is much more common and can lead to many problems mentioned later in the article. If you are experiencing symptoms of deficiency or know that your vitamin B6 levels are too low, correcting a deficiency is the main benefit of pyridoxal phosphate supplements.
Minor benefits
Reduced symptoms of PMS – Doses of 50-100 mg can slightly but reliably lower the symptoms of premenstrual syndrome (PMS). This is likely because high estrogen levels increase your vitamin B6 needs.
Reduced breast tenderness – This effect was only found in one study that didn’t have a placebo group and needs to be replicated. However, in that study, vitamin B6 supplements were very effective at reducing breast tenderness. This likely applies to all forms of B6 supplements, including pyridoxal phosphate.
Intensified dreams – In one study, individuals who took 100-250 mg reported having more vivid dreams. This may be a great thing for psychological health because dreams have the potential to improve long-term well-being.
Unproven benefits
There is not enough evidence that pyridoxal phosphate notably affects these health metrics, or the science shows little to no efficacy in these areas.
Weight loss and fat loss – Taking the supplement doesn’t notably affect weight loss or burning of fat.
Skin quality – Unfortunately, pyridoxal phosphate doesn’t seem to help with acne, wrinkles, or other skin problems. It also doesn’t help hydrate the skin or keep it elastic.
Blood flow – Scientific studies have never shown a significant effect on blood flow.
Blood pressure – There is no high-quality evidence that pyridoxal phosphate supplements affect blood pressure to any significant degree.
DNA protection – The supplement has not been shown in human studies to protect DNA from oxidative damage.
Inflammation – The supplement doesn’t significantly affect CRP (C-reactive protein) or other markers of inflammation.
Triglycerides – There is no significant influence, or at least it has never been proven.
Testosterone – The supplement does not significantly affect DHT, free testosterone, or total testosterone levels.
Cholesterol – Pyridoxal phosphate has no direct effect on HDL or LDL cholesterol levels.
Cancer – The supplement has never been shown in reliable human studies to affect cancer rates or tumor growth.
Thyroid hormones – There is no significant interaction between the supplement and serum T3 and T4.
Strength and muscle growth – Pyridoxal phosphate does not help you increase strength or muscle mass faster. Reliable human studies have never shown this effect.
Asthma – The supplement has not been shown to help with asthma to a significant degree.
Power output during exercise – The supplement does not directly influence power output during aerobic or resistance training. It does not impact VO2 max or aerobic endurance either.
Kidney function – The supplement does not significantly change kidney function biomarkers.
Sleep quality – The supplement does not directly improve sleep quality. It also does not seem to affect sleep duration.
Stress and anxiety – The supplement does not affect cortisol levels, at least not directly.
Metabolic rate – The supplement does not speed up your metabolism or slow it down.
Possible side effects
These side effects are dose-dependent. The risk for them increases (often linearly but sometimes exponentially) as you increase the dose. Some of the side effects only apply to very high doses.
Lung cancer – The biggest concern associated with vitamin B6 supplements is an increased risk of lung cancer. This effect applies mainly to smokers, where vitamin B6 supplements can increase the risk by up to 82%. We do not yet know if B6 supplements increase the risk of lung cancer in people who don’t smoke. Fortunately, the same study that discovered the 82% increased risk in smokers also found no correlation between vitamin B6 supplements and lung cancer risk in non-smokers. However, we need more studies to know for sure.
Vitamin B6 toxicity – While toxicity is rare, taking high amounts of pyridoxal phosphate could lead to some health problems over time. These include numbness to touch or temperature, tingling, burning or pain in the hands, feet, arms, or legs, and loss of full control over body movements. Fortunately, the symptoms of toxicity almost always disappear right after one stops taking high doses. However, extremely high doses could cause irreversible sensory ganglion neuropathy (nerve damage). This is why it’s best to avoid very high doses. Specifically, you want to stay below 50-100 mg a day unless you have a great reason to take more.
Contamination – Contaminated supplements are uncommon in the USA and other well-regulated countries. However, if you wish to buy products from China, India, or other countries without strict regulations, beware that the supplements may be contaminated. Either way, you need to choose the brand you order from wisely. It is highly recommended to check the certificates or read through some reviews for the specific product before you buy it. The FDA (Food and Drug Administration) has the power to regulate dietary supplements but can only do so after they have been on the market for a while. That’s because supplement companies are not obligated to announce to the FDA when releasing a new product on the market. The FDA has to discover the product and test it for potential impurities, which can take a lot of time. During that time, the supplement can be sold on the market even if it’s impure. Also, the supplement companies can change their manufacturers at any time without announcing it to the FDA.
Who should not take pyridoxal phosphate?
You should probably avoid taking the supplement if you:
already consume enough B6 from food
smoke (since P5P supplements significantly increase the risk for lung cancer in smokers)
experience a severe adverse reaction after taking the supplement
are on a tight supplement budget (since there are more cost-effective supplements on the market for most people)
Who will benefit the most?
You should consider taking the supplement if you:
experience symptoms of deficiency, or you know you are deficient based on blood tests
don’t get enough vitamin B6 from food (the easiest way to find out how much of the nutrient you are getting in your diet is to track your food intake for a while with Cronometer.com)
are deficient in riboflavin (since riboflavin is needed to convert pyridoxine from plants to pyridoxal, the active form)
have higher estrogen from oral contraceptives, pregnancy, or the peaks at ovulation and just before menstruation (it increases your need for vitamin B6)
are older (people over 50 years of age need 10-20% more vitamin B6)
consume a lot of sulfite from food additives (sulfite destroys B6)
eat a diet high in animal protein (high intake of animal protein increases sulfite levels in the body + vitamin B6 is necessary for turning ammonia, a byproduct of excess protein, into urea)
experience chronic inflammation (not only can this be a sign of vitamin B6 deficiency, but inflammation also increases your need for B6)
take NSAIDs (nonsteroidal anti-inflammatory drugs can deplete you of the vitamin)
suffer from one of a few rare genetic disorders that require very high amounts of B6 to correct
Forms of vitamin B6 supplements
Vitamin B6 comes in 6 forms: pyridoxine, pyridoxal, pyridoxamine, and their phosphorylated forms. The most common supplemental forms are:
Pyridoxine HCl – This is the cheapest, the most studied, and the most popular form. While pyridoxine HCl is effective at increasing your levels of vitamin B6, whether or not you absorb it well depends on how healthy your liver is. You also need adequate amounts of riboflavin for the conversion of pyridoxine to pyridoxal and taking this form increases your need for riboflavin.
Pyridoxal 5′-phosphate (P5P) – This is the active form of vitamin B6. P5P is a preferred form because almost everyone absorbs it well as it does not need to go through any conversion to become bioavailable.
Pyridoxamine dihydrochloride – This form is not as popular as pyridoxine HCl or P5P so we don’t know as much about how it affects the body. From what we do know, pyridoxamine is closer to pyridoxal than pyridoxine as far as its effects and absorption. It appears more effective than pyridoxine HCl for increasing active vitamin B6 levels in the body.
From these forms, P5P is the best one to take for most people.
Symptoms of vitamin B6 deficiency
The most common signs of deficiency include:
irritability
depression
confusion
anxiety
insomnia
skin problems
getting sick more often
arthritis
anemia
high homocysteine levels, especially after food
kidney stones
faster age-related cognitive decline
morning sickness
Keep in mind that these signs are just indications of a deficiency. If you experience some or even most of them, it does not necessarily mean you need more vitamin B6. On the other hand, some people may be deficient even though they are completely asymptomatic.
With that said, if you experience many or most of these symptoms, there is a high chance that you are not getting enough vitamin B6. The more of these symptoms you have and the more severe they are, the more likely you are to have a deficiency.
How much vitamin B6 should you take?
The RDA (recommended daily allowance) for this nutrient is 1.3 mg for most adults. As you age, your need for vitamin B6 increases. The RDA for men over 50 is 1.7 mg and for women over 50, it is 1.5 mg. Since pregnancy and lactation also increase your need, the RDA is 1.9 mg for pregnant women and 2.0 mg for lactating women. This should be more than enough to avoid deficiency.
2-10 mg appears to be the best dose to take for most people. This amount should provide most of the benefits without meaningful side effects.
Beware that some things increase your need for vitamin B6. These include high estrogen levels, NSAIDs, inflammation, and more.
The upper safety limit is around 100 mg. Higher doses may cause problems if you take the supplement for a prolonged period. Do not take more than this amount unless you have a great reason to do so.
Unless you are trying to correct a severe deficiency, taking more than 50 mg daily should not be necessary. Also, the higher the dose you take, the higher the risk for side effects.
Food sources of vitamin B6
Just like with vitamin A and a few other nutrients, our body cannot utilize the plant-based form of vitamin B6, pyridoxine. We need to convert pyridoxine into the animal-based form, pyridoxal. This conversion requires riboflavin and a healthy liver. If those two things are in place, you can expect around half of the pyridoxine to convert into pyridoxal. If not, you may be unable to convert any pyridoxine to pyridoxal.
Cooking destroys about 25-40% of vitamin B6, depending on the type of food and how you cook it.
Nutritional yeast is by far the richest food source of B6. As little as one teaspoon should provide more than enough vitamin B6. Other good sources include organ meats, whole grains, legumes, and many types of nuts and seeds.
When it comes to getting enough vitamin B6, nutritional yeast is the only type of food that provides a significantly higher amount than the other sources. If you eat many types of whole foods, chances are the B6 you are consuming will be more or less distributed among all of them.
The easiest way to find out how much vitamin B6 you are getting in your diet is with Cronometer.com – this free app allows you to track all vitamins, minerals, and more.
Best time to take pyridoxal phosphate
Pyridoxal phosphate is water-soluble, which means you don’t have to take it with food to absorb it well.
Whether you take the supplement in the morning or the evening doesn’t matter. It does not interrupt your sleep in any way.
Interactions with other supplements
Riboflavin Riboflavin is needed to convert pyridoxine to pyridoxal.
L-Dopa Vitamin B6 is needed for the synthesis of dopamine from L-Dopa. Thus, L-Dopa increases your need for the vitamin.
5-HTP You need enough vitamin B6 to synthesize serotonin from 5-HTP.
Other B vitamins Vitamin B6 can be especially synergistic with folate (vitamin B9) and cobalamin (vitamin B12). Together, they may improve mood, well-being, brain health, and sleep quality.
NSAIDs Nonsteroidal anti-inflammatory drugs can deplete your vitamin B6 levels and increase your need for the nutrient.
Where to buy pyridoxal phosphate
Amazon seems to be the best option for ordering pyridoxal phosphate supplements in most countries. They offer some very affordable products backed by many positive reviews. Also, you can choose from a wide range of brands without having to search through other markets on the internet.
Beware some brands display the dosage per serving instead of per pill or capsule. Therefore, you may accidentally buy something less potent than you intended. Do not fall for this marketing trick.
FAQ
You can take the supplement daily and do not need to cycle it. However, it is certainly not a problem if you don’t take it daily. Not taking the supplement every once in a while could lead to better absorption, but no studies have proven this.
All of these options are fine. The two most important things to consider are the price and dosing. Powders are almost always the cheapest form. However, to dose them correctly, you may need a highly accurate scale (preferably 0.001g). You can get one for as little as $20 from Amazon. Dosing the powders also takes some time that can add up over months or years. The disadvantage of capsules is that they are sometimes made of unethical ingredients, such as bovine gelatine.
Yes. The nutrient doesn’t impact your sleep in any negative way in the short term.
Pyridoxal phosphate rarely goes bad, but it can lose potency over time.
Keep pyridoxal phosphate supplements in a cold, dark, and dry place, and they will remain just as potent for many months or even years.
The supplement doesn’t directly reduce acne, unfortunately.
Yes. The biggest concern associated with vitamin B6 supplements is an increased risk of lung cancer. This effect applies mainly to smokers, where vitamin B6 supplements can increase the risk by up to 82%. We do not yet know if B6 supplements increase the risk of lung cancer in people who don’t smoke. Fortunately, the same study that discovered the 82% increased risk in smokers also found no correlation between vitamin B6 supplements and lung cancer risk in non-smokers. However, we need more studies to know for sure.
While vitamin B6 toxicity is rare, taking high amounts of pyridoxal phosphate could lead to some health problems over time. These include numbness to touch or temperature, tingling, burning or pain in the hands, feet, arms, or legs, and loss of full control over body movements. Fortunately, the symptoms of toxicity almost always disappear right after one stops taking high doses. However, extremely high doses could cause irreversible sensory ganglion neuropathy (nerve damage). This is why it’s best to avoid very high doses. Specifically, you want to stay below 50-100 mg a day unless you have a great reason to take more.
Pyridoxal 5′-phosphate is the active form and the best one to take. While pyridoxine HCl can be almost just as good, people with poor liver health or riboflavin deficiency may not absorb much of it.
The most common reason people become deficient is that they don’t get enough vitamin B6 from their diet. However, many things can hurt your vitamin B6 status and increase your need for this nutrient. These include high estrogen levels, NSAIDs, chronic inflammation, riboflavin deficiency, and some rare genetic disorders.
You may need more of the nutrient if you: – experience signs of deficiency, or know that you are deficient from blood tests – don’t get enough vitamin B6 from food (the easiest way to find out how much of the nutrient you are getting in your diet is to track your food intake for a while with Cronometer.com) – are deficient in riboflavin (since riboflavin is needed to convert pyridoxine from plants to pyridoxal, the active form) – are older (people over 50 years of age need 10-20% more vitamin B6) – have higher estrogen from oral contraceptives, pregnancy, or the peaks at ovulation and just before menstruation (it increases your need for vitamin B6) – eat a diet high in animal protein (high intake of animal protein increases sulfite levels in the body + vitamin B6 is necessary for turning ammonia, a byproduct of excess protein, into urea) – experience chronic inflammation (not only can this be a sign of vitamin B6 deficiency, but inflammation also increases your need for B6) – suffer from one of a few rare genetic disorders that require very high amounts of B6 to correct – consume a lot of sulfite from food additives (sulfite destroys B6) – take NSAIDs (nonsteroidal anti-inflammatory drugs can deplete you of the vitamin)
The half-life of pyridoxal phosphate is about 30 days. The nutrient stays in your system for a long time after you take it.
In the long-term, it typically takes around a month after you start taking the supplement to start noticing the benefits.
Pyridoxal 5′-phosphate can be derived both from plant-based sources and animals. While most P5P supplements on the market are vegan-friendly, it is important to check the label to make sure.
Pyridoxal phosphate is water-soluble, which means you don’t have to take it with food to absorb it well.
No, it doesn’t. The supplement does not interfere with fasting in any significant way.
References
Most of the information provided in this guide is supported by scientific research that can be found and verified in the PubMed medical library. We excluded from consideration studies that are either confounded or have a high conflict of interest.
