Evidence: High Potential Benefits: High Safety:High
TABLE OF CONTENTS
What is vitamin B9?
Folinic acid, also known as leucovorin or calcium folinate, is a form of vitamin B9 that naturally occurs in food. This form is similar to methylfolate, another popular form of vitamin B9. Folinic acid is a little better at supporting anemia prevention than methylfolate, but the difference is small. Folinic acid supplements are most helpful if you are deficient in the nutrient. If you already get enough folate from food, you should not need to take the supplement. However, it may still be able to improve some aspects of your health beyond the baseline. This article is about the main benefits of folinic acid, 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 B9 deficiency – Folate 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 B9 levels are too low, correcting a deficiency is the main benefit of folinic acid supplements.
Preventing neural tube defects in infants – Adequate folate is needed to prevent neural tube defects, a category of birth defects that include spina bifida and anencephaly. These defects can be fatal or lead to life-long paralysis. It can be harder for pregnant and lactating women to get enough vitamin B9 since their needs go up by 20-35%. This is why vitamin B9 is sometimes called a “pregnancy supplement.”
Minor benefits
Reduced symptoms of depression – This effect is most significant for women but appears to be notable for men as well. While the exact cause for this is unknown, folinic acid has been shown to have an impact on serotonin pathways and appears to enhance SSRI therapy so the effect seems to be mostly serotonin-related.
Reduced symptoms of schizophrenia – This benefit has been observed in people with a vitamin B9 deficiency and may or may not apply to those who are not deficient.
Reduced homocysteine – In one study, taking 400 mcg to 5 mg of folic acid over 6 weeks reduced homocysteine levels in most participants. This effect almost definitely applies to other forms of B9 supplements, including folinic acid.
Increased blood flow – This effect only seems to apply to high doses (1-5 mg) while doses lower than that are ineffective at increasing blood flow.
Unproven benefits
If you are deficient in vitamin B9, folinic acid can help improve some of these health metrics. However, there is not enough evidence that folinic acid supplements notably affect these health metrics in non-deficient people, or the science shows little to no efficacy in these areas.
Skin quality – Unfortunately, folinic acid supplements don’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 the 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 observed.
Brain health and cognition – The supplement does not directly improve brain health and cognitive abilities.
Testosterone – The supplement does not significantly affect DHT, free testosterone, or total testosterone levels.
Cholesterol – The supplement 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.
Well-being – Supplementation with vitamin B9 doesn’t appear to increase subjective well-being unless paired with SSRIs. However, the supplement could improve your well-being if you are deficient.
Weight loss and fat loss – Taking the supplement doesn’t notably affect weight loss or burning of fat.
Strength and muscle growth – The supplement 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.
Masking vitamin B12 deficiency – Folate can hide thy symptoms of vitamin B12 deficiency to some extent. When you are deficient in vitamin B12, taking additional folate also seems to exacerbate neurological damage caused by the deficiency.
Worsened mental and emotional well-being – Some people report negative mental and emotional reactions after taking supplemental vitamin B9. This especially applies to those who are deficient in vitamin B12.
Increased risk for cancer – This effect applies to doses of more than 1 mg of folinic acid daily for a prolonged period. Lower doses or other forms may and may not increase the risk of cancer. This side effect applies particularly to colon cancer among the elderly.
Vitamin B9 toxicity – While acute toxicity is rare and doesn’t seem to be a problem even if you take doses as high as 15 mg, taking high amounts of vitamin B9 could lead to some health problems over time. It’s best to avoid very high doses since we don’t yet know whether or not they are safe to take over a long period. Specifically, you want to stay below 1 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 folinic acid?
You should probably avoid taking the supplement if you:
already consume enough folate from food
experience a severe adverse reaction after taking the supplement
are deficient in vitamin B12
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 B9 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)
drink alcohol
smoke cigarettes
get exposed to lots of sunlight
have been diagnosed with cancer (cancer cells may steal folate to fuel their growth)
have certain genes that increase your need for vitamin B9 (specifically, the most important ones are MTHFR, MTHFD1, SLC19A1, and DHFR)
are pregnant or lactating (pregnancy increases your need by about 200 mcg and lactation by about 100 mcg)
Other forms of vitamin B9
The 3 main forms of vitamin B9 supplements include:
Folic acid – This form is the cheapest, the most shelf-stable, and the most popular. Unfortunately, it is also the worst form to take for most people. This is because there might be harmful effects of folic acid staying in the blood that hasn’t been converted to folate. While folic acid is around 70% more absorbable than folate from food, people with low DHFR activity absorb folic acid poorly. Also, the body can only absorb around 260 mcg DFE (dietary folate equivalents) at once from folic acid supplements.
Folinic acid – Also called leucovorin or calcium folinate, this is one of the forms of B9 that naturally occurs in food. Folinic acid is mainly used to decrease the toxic effects of methotrexate and pyrimethamine. It is a little better at supporting anemia prevention than methylfolate, but the difference is small.
Methylfolate – Methylfolate (also known as levomefolic acid, MTHF, 5-MTHF, L-5-MTHF, L-methylfolate, and L-5-methyltetrahydrofolate) is another natural form of vitamin B9. Methylfolate is better at supporting methylation than both folic acid and folinic acid. This is the best form to take for people with low MTHFR activity.
Methylfolate and folinic acid are both superior to folic acid, especially for people with low DHFR activity. Methylfolate is better than folinic acid for those who also have low MTHFR activity so it is probably a safer bet. However, you can also take both methylfolate and folinic acid since they enter the folate cycle at different points, offering full pathway support.
Symptoms of vitamin B9 deficiency
The most common signs of deficiency include:
anger
depression
anxiety
allergies in response to lots of different foods
trouble concentrating
poor sleep quality
weakness
tiredness
macrocytic, megaloblastic anemia
shortage of breath
paleness
irregular heartbeat
elevate homocysteine when fasting
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 B9. 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 B9. The more of these symptoms you have and the more severe they are, the more likely you are to have a deficiency.
How much folinic acid should you take?
The RDA (recommended daily allowance) for this nutrient is 400 mcg DFE for most adults, 600 mcg DFE for pregnant women, and 500 mcg for lactating women.
DFE stands for “dietary folate equivalents.” The reason why DFE is a preferred way to measure vitamin B9 intake is that different forms of vitamin B9 differ in how well you can absorb them. In general, 1 mcg of folate from food or methylfolate supplements equals 1 mcg of DFE. Since folic acid is more potent, you need as little as 200-240 mcg to achieve the RDA of 400 mcg DFE.
While these amounts should be enough to prevent a deficiency, it would be more accurate to shoot for 200 mcg for every 1000 calories you are consuming. If you are pregnant or lactating, shoot for 250-300 mcg per 1000 kcal instead.
400 mcg 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 B9. These include smoking, alcohol, sun exposure, and genetics (the most important genes that can alter your folate status include MTHFR, MTHFD1, SLC19A1, and DHFR).
On the other hand, some things decrease your need for folate. For example, creatine and choline can partially replace folate in some of its functions. Taking creatine can decrease your need for folate by up to 50%.
The upper safety limit for folinic acid is 1 mg per day. This amount was based on rare hypersensitivity reactions and on cases where supplemental folate seemed to *cause* patients with vitamin B12 deficiency to start developing neurological problems. Do not take more than this amount unless you have a great reason to do so.
Taking more than 400-800 mcg daily should not be necessary and is not recommended unless you have a great reason to do so. The higher the dose you take, the higher the risk for side effects.
Food sources of vitamin B9
Legumes, liver, and green vegetables are the richest food sources of folate. These food sources should provide more than enough vitamin B9 in 200 grams, sometimes even less.
In general, plant foods contain significantly more folate than animal foods. The only two exceptions to this rule are liver and pasture-raised eggs. As for pasture-raised eggs, the amount of folate is fairly inconsistent but if you know that the chicken eats mostly grass and leafy greens, its eggs are probably a good source of vitamin B9. Factory-farmed eggs don’t contain much folate if any.
While it is hard to become deficient in folate on a plant-based diet, it can be equally as hard to get the optimal amount of vitamin B9 if you eat mostly animal foods.
One problem with vitamin B9 from plant foods is that it gets destroyed when you freeze or can the food sources. Therefore, frozen vegetables or canned legumes may not contain any folate and should not be counted.
Also, cooking destroys around 25% of vitamin B9. Another 25% or so get lost if you boil the sources and then don’t drink the water. This is because vitamin B9 is water-soluble. On the other hand, sprouting increases the vitamin B9 content in vegetables by around 500%.
Enriched flour also contains vitamin B9 in many countries but it is in a form of folic acid.
The easiest way to find out how much vitamin B9 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 folinic acid
Folinic acid 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
B vitamins Vitamins B1, B2, B3, B5, B6, and B12 all help support folate in the methylation process. The same also applies to iron, phosphorus, magnesium, potassium, and zinc. Being deficient in one or multiple of these means you won’t be able to utilize vitamin B9 optimally.
Vitamin B12 Not only does vitamin B12 support some processes of folate related to methylation but those who take high doses of folate are more likely to experience side effects if they are deficient in vitamin B12.
Methotrexate Methotrexate is used to treat cancer, rheumatoid arthritis, and psoriasis by antagonizing folate. In other words, it can quickly make you deficient in vitamin B9.
SSRIs Vitamin B9 increases the effects of SSRIs. This effect is most significant in women and not as significant but still notable in men.
Alcohol Alcohol interferes with vitamin B9 absorption and can make you deficient in the nutrient.
Where to buy folinic acid
Amazon seems to be the best option for ordering folinic acid 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.
The supplements rarely go bad, but they can lose potency over time.
Keep folinic acid 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.
While acute vitamin B9 toxicity is rare and doesn’t seem to be a problem even if you take doses as high as 15 mg, taking high amounts of folinic acid could lead to some health problems over time. It’s best to avoid very high doses since we don’t yet know whether or not they are safe to take over a long period. Specifically, you want to stay below 1 mg a day unless you have a great reason to take more.
Methylfolate and folinic acid are both superior to folic acid, especially for people with low DHFR activity. Methylfolate is better than folinic acid for those who also have low MTHFR activity so it is probably a safer bet. However, you can also take both methylfolate and folinic acid since they enter the folate cycle at different points, offering full pathway support.
The most common reason people become deficient is that they don’t get enough folate from food. However, many things can hurt your vitamin B9 status and increase your need for this nutrient. These include alcohol, smoking, excess sunlight, and certain genetics (specifically, the most important ones are MTHFR, MTHFD1, SLC19A1, and DHFR).
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 folate 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) – drink alcohol – smoke cigarettes – get exposed to lots of sunlight – have certain genes that increase your need for vitamin B9 (specifically, the most important ones are MTHFR, MTHFD1, SLC19A1, and DHFR) – have been diagnosed with cancer (cancer cells may steal folate to fuel their growth) – are pregnant or lactating (pregnancy increases your need by about 200 mcg and lactation by about 100 mcg)
Folinic acid stays in your system for about 24 after you take it.
In the long-term, it typically takes about a month after you start taking the supplement to start noticing the benefits.
The vast majority of folinic acid supplements on the market are vegan-friendly.
This form of vitamin B9 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.
