CCL Supplements Advanced B-12 Spray Review
CCL Supplements Advanced B-12 Spray, sold as Advanced Vitamin B12 Complex, is a sublingual (under-the-tongue) liquid vitamin B12 supplement. It comes in a metered pump bottle in berry flavor, in 2 oz and 4 oz sizes. The 4 oz size is listed as 120 servings. It is made in a GMP-certified facility in the USA and is marketed as vegan and vegetarian friendly. According to the listing, the ingredients are vitamin B12 as methylcobalamin, folic acid, pyridoxine HCl (vitamin B6), purified water, glycerine, xylitol, citric acid and berry flavor. Methylcobalamin is one of the two active coenzyme forms of B12. It is the non-synthetic alternative to cyanocobalamin, which the body must convert before it can use it. B12 acts as a cofactor in two main pathways. In the cytosol, methylcobalamin is the cofactor for methionine synthase. That enzyme remethylates homocysteine to methionine, which supports methylation reactions in the nervous system and keeps homocysteine levels down. This reaction depends on folate, which is why folic acid is paired with B12 here. In mitochondria, a related form (adenosylcobalamin) is needed to convert methylmalonyl-CoA to succinyl-CoA, which links fatty acid and amino acid breakdown to energy production. B12 is also required for normal red blood cell formation and for maintaining the myelin sheath around nerves. Vitamin B6 supports amino acid metabolism and neurotransmitter synthesis, and works in the same homocysteine-clearing network. The spray format is the product's main feature. The brand says the liquid is absorbed through the mucous membranes of the mouth and goes into the bloodstream without passing through digestion. It also says "nano technology" gives much higher absorption than pills, capsules, powders and gummies. The marketing claims the effects start within minutes. It also says a spray is better than drops, because nothing is lost to the dropper. Independent evidence is more cautious. Oral B12 absorption works two ways. An intrinsic-factor pathway in the gut absorbs only about 1.5 mcg at a time. A passive diffusion pathway absorbs roughly 1% of larger doses, and that pathway is why high-dose oral B12 can correct deficiency even in people who can't absorb B12 normally. Studies have generally found sublingual B12 comparable to swallowed B12, not clearly superior. The "nano" and "within minutes" claims are manufacturer claims without published data. Typical users are vegans and vegetarians, older adults, people on a med or acid-reducing drugs, and anyone with low energy or a diagnosed B12 deficiency. Use is a few sprays under the tongue, held briefly before swallowing, which makes the dose adjustable. Check with a clinician before using it to treat suspected deficiency, since numbness or memory loss needs proper testing. B12 supplements are also not a replacement for treating pernicious anemia.
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Study, Trial or Testing Result Summary
Members Only48 human studies · 11 improved
4 of these 48 human studies gave the ingredient by injection, not by mouth.
This spray has vitamin B12, folic acid and vitamin B6, and the energy evidence for all three is weak. For vitamin B12, a review of 16 trials in people without a deficiency found no benefit for thinking or mood, and only one trial measured fatigue, too few to judge [1]. B12 injections did no better than placebo in people with chronic fatigue syndrome [2] or for voice fatigue in singers [3]. A supplement mix containing B12 did not change fatigue in dialysis patients [4]. For folic acid, results are mixed. Adding folic acid, a drug called pentoxifylline, or both to standard care lowered fatigue in people with kidney disease [5]. Adding folic acid to iron did not change fatigue in women with anemia after childbirth [6]. One dose of a pre-workout drink containing folic acid raised reported energy, but it held many other ingredients [7]. For vitamin B6, a large three-year trial of low-dose B vitamins found no gain in vitality [8], and a trial in adults with mild insomnia found no help for physical fatigue [9]. A small trial in women with premenstrual symptoms found 50 milligrams a day eased tiredness, a far higher dose than in this spray [10]. At two servings a day, the folic acid is above the recommended daily limit, so members may want to take less. Animal and cell studies are never counted.
See all 48 studies →Hide the studies
- Across 16 randomized trials with 6276 people without vitamin B12 deficiency, B12 did not improve thinking or depression, and only one trial looked at fatigue so it could not be analyzed.Effects of Vitamin B12 Supplementation on Cognitive Function, Depressive Symptoms, and Fatigue: A Systematic Review, Met…
- A review of 13 small trials (85 people with McArdle disease, a muscle energy disorder) found no exercise benefit from vitamin B6 or several other treatments.Pharmacological and nutritional treatment for McArdle disease (Glycogen Storage Disease type V).
- In about 2,000 heart disease survivors given low-dose B vitamins including 3 mg vitamin B6 for about 3 years, quality of life and vitality did not improve, and activity limits from emotional problems were slightly worse.B vitamin and/or n-3 fatty acid supplementation and health-related quality of life: ancillary findings from the SU.FOL.O…
- In 311 people on a med agonist therapy, a daily fruit smoothie for 16 weeks did not change fatigue symptoms, fitness or folate levels compared with standard treatment alone.Read the study on PubMed (40877839) →
- In 172 dialysis patients given a multinutrient mix including vitamin B6 for 12 weeks, fatigue and quality of life did not differ from placebo, though some heart rate variability measures improved.Effects of nutritional supplementation on fatigue, and autonomic and immune dysfunction in patients with end-stage renal…
- In 171 adults with mild insomnia, a blend containing vitamin B6 for 2 weeks did not beat placebo on sleep quality or physical fatigue.Exploring the Effect of Lactium™ and Zizyphus Complex on Sleep Quality: A Double-Blind, Randomized Placebo-Controlled Tr…
- In 112 women with anemia after childbirth, adding 1 mg of folic acid daily to iron for 4 weeks did not change fatigue scores, hemoglobin or health status compared with iron alone.A randomized controlled trial examining the addition of folic acid to iron supplementation in the treatment of postpartu…
- In 100 adults taking 240 mg vitamin B6 before bed for five days, dream recall rose but sleep was unaffected, while a B complex group reported worse sleep quality and more tiredness on waking.Effects of Vitamin B6 (Pyridoxine) and a B Complex Preparation on Dreaming and Sleep.
- In 80 people with chronic kidney disease, adding folic acid and/or pentoxifylline to standard care for 6 months significantly reduced fatigue scores compared with standard care alone.The potential adding therapeutic effect of pentoxifylline and/or folic acid for chronic kidney disease patients: randomi…
- In 65 people with chronic fatigue syndrome, a daily beta-glucan, vitamin D3, 1.05 mg vitamin B6 and zinc supplement for 36 weeks improved cognitive fatigue versus baseline.Yeast Beta-Glucan Supplementation with Multivitamins Attenuates Cognitive Impairments in Individuals with Myalgic Enceph…
- In 65 adults with self-reported gluten sensitivity following a gluten-free diet, average folic acid intake from food was below recommended levels and tiredness was among the most common symptoms, but this baseline dietary report did not test any folic acid supplement for energy.Dietary and symptom assessment in adults with self-reported non-coeliac gluten sensitivity.
- In 63 women with premenstrual symptoms (32 finished), 50 mg of vitamin B6 daily for three months in a crossover design improved emotional symptoms including tiredness, but had no significant effect on other symptom types.Pyridoxine (vitamin B6) and the premenstrual syndrome: a randomized crossover trial.
- In 54 cancer patients with hand-foot skin reactions, topical pyridoxine for 6 weeks did not help the skin condition but was linked to lower fatigue and better quality of life than placebo.A pilot randomized double-blind, placebo-controlled study on the effects of the topical application of pyridoxine on pal…
- In 41 trained cyclists, 4 weeks of a combination supplement including 2.5 mcg B12 did not improve aerobic or anaerobic performance or fatigue measures compared with placebo, though blood lactate was lower after hard exercise.l-Carnitine and Alpha-Lipoic Acid Fail to Improve Anaerobic and Aerobic Performance in Trained Cyclists Despite a Reduct…
- In 33 soldiers over 12 days, ration pack feeding led to more fatigue than fresh food, and folate status declined in all groups; folic acid was not tested as a supplement.The physiological and psychological effects of combat ration feeding during a 12-day training exercise in the tropics.
- In 30 young women with premenstrual syndrome, both groups took vitamin B6 and calcium for 3 months, and the benefit for fatigue was credited to added treadmill exercise, so the effect of vitamin B6 itself on energy could not be determined.Effect of aerobic exercise on premenstrual symptoms, haematological and hormonal parameters in young women.
- In 25 healthy adults, a single dose of a pre-workout supplement containing folic acid raised self-reported energy and vigor and improved cognitive scores versus placebo, with no change in lifting or sprint performance.Effects of acute ingestion of a pre-workout dietary supplement with and without p-synephrine on resting energy expenditu…
- In 25 trained people, a pre-workout drink containing folic acid and caffeine for 7 days helped maintain some strength and lifting measures versus placebo but did not change cycling time-trial performance.Short-Term Effects of a Ready-to-Drink Pre-Workout Beverage on Exercise Performance and Recovery.
- In 20 singers with mild vocal symptoms, a single 1000 mcg B12 injection did not improve voice fatigue or singing measures more than a placebo injection.Effect of Vitamin B12 Injection on the Vocal Performance of Professional Singers: A Randomized, Double-blind, Placebo-Co…
- In 15 adults with chronic fatigue syndrome, an injected bovine liver extract containing folic acid and vitamin B12 did not improve symptoms beyond placebo in a double-blind crossover trial, and the placebo response was strong.Liver extract-folic acid-cyanocobalamin vs placebo for chronic fatigue syndrome.
- In a double-blind crossover trial of seven trained cyclists, three weeks of a supplement containing vitamin B6 with other energy-cycle compounds did not extend time to exhaustion or speed recovery compared with placebo.Tricarboxylic-acid-cycle intermediates and cycle endurance capacity.
- In 134 patients after brain aneurysm treatment, adding glycerol fructose to vitamin B6 improved fatigue and recovery scores versus vitamin B6 alone, so the effect of B6 itself on energy cannot be separated.Glycerol fructose combined with vitamin B6 is beneficial to postoperative recovery of patients with cerebral aneurysm.
- In 73 children and young people with mild thalassemia, 3 months of carnitine with or without 1 mg folic acid reduced bone pain and muscle weakness, and folic acid raised red cell folate; the benefit was attributed mainly to carnitine.Determining and surveying the role of carnitine and folic acid to decrease fatigue in β-thalassemia minor subjects.
- In 23 iron-deficient women without anemia, a daily food-derived iron supplement containing folate for 8 weeks improved self-reported fatigue and energy, though the study had no control group.A Food-Derived Dietary Supplement Containing a Low Dose of Iron Improved Markers of Iron Status Among Nonanemic Iron-Def…
- In a chart review of 2142 people with fibromyalgia, 42.4% had vitamin B12 deficiency, and deficiency was linked to higher odds of fatigue (odds ratio 1.39) after adjusting for vitamin D.Association of Vitamin B12, Vitamin D, and Thyroid-Stimulating Hormone With Fatigue and Neurologic Symptoms in Patients …
- In colorectal cancer patients, higher circulating vitamin B6 (pyridoxal 5'-phosphate) six months after diagnosis was linked to less fatigue and better quality of life.Circulating B-vitamin biomarkers and B-vitamin supplement use in relation to quality of life in patients with colorectal…
- In adults over 65 followed for about 3.5 years, those with the lowest dietary vitamin B6 intake had higher odds of developing frailty, including exhaustion, than those with the highest intake.Low vitamin intake is associated with risk of frailty in older adults.
- In a survey of 815 older Japanese adults, folic acid intake from diet was lower in people classed as prefrail, but this study did not measure energy and did not test folic acid supplementation.Association of Protein and Magnesium Intake with Prevalence of Prefrailty and Frailty in Community-Dwelling Older Japane…
- In a retrospective study of 689 children without complaints, 23.2% had vitamin B12 deficiency and it was linked to vitamin D deficiency, but no supplement was tested for energy.Is There An Association Between Vitamin B12 Level and Vitamin D Status in Children?
- In 335 older adults, vitamin B12 levels were not associated with frailty, and no supplement was tested.Association between serum vitamin B12 level and frailty in older adults.
- About one-third of pregnant women taking doxylamine-pyridoxine for nausea reported tiredness, sleepiness or drowsiness as side effects, with no link to dose.The safety of higher than standard dose of doxylamine-pyridoxine (Diclectin) for nausea and vomiting of pregnancy.
- In recently bereaved gay men, low blood vitamin B6 was linked to more fatigued and depressed mood, though this was a cross-sectional association and not a supplement trial.Plasma pyridoxine deficiency is related to increased psychological distress in recently bereaved homosexual men.
- Women with fibromyalgia had lower vitamin B12 levels than 58 healthy women, and lower levels were linked to more tender points, though this study did not test supplements.Could ferritin, vitamin B12, and vitamin D play a role in the etiopathogenesis of fibromyalgia syndrome?
- In people with irritable bowel syndrome, lower intake of vitamin B6 was associated with more fatigue and more non-bowel symptoms.Poor intake of vitamins and minerals is associated with symptoms among patients with irritable bowel syndrome.
- In a study of 101 people with multiple sclerosis, lower dietary folate intake was linked to higher fatigue scores, but this cross-sectional study cannot show that folate changes fatigue.Dietary intake of nutrients and its correlation with fatigue in multiple sclerosis patients.
- In COVID-19 survivors with ongoing fatigue, a multicomponent supplement containing vitamin B6 and B1 over 8 weeks was associated with better handgrip strength, walking and quality of life than the control group.Effects of a New Multicomponent Nutritional Supplement on Muscle Mass and Physical Performance in Adult and Old Patients…
- Vitamin B12 levels were normal in 55 people with primary fibromyalgia, who reported muscle fatigue as one of their most disabling symptoms.Primary fibromyalgia. A clinical and laboratory study of 55 patients.
- In a 7-day diary study of 20 adults with hypophosphatasia and 20 matched controls, vitamin B6 intake did not differ significantly between the groups, and the study did not link B6 to energy levels.Mineral Intake and Clinical Symptoms in Adult Patients with Hypophosphatasia.
- In a survey of 38 people with chronic fatigue syndrome or fibromyalgia, those who rated themselves most improved had taken higher daily amounts of oral folic acid along with frequent vitamin B12 injections, but the survey cannot show folic acid caused the improvement.Response to vitamin B12 and folic acid in myalgic encephalomyelitis and fibromyalgia.
- In a retrospective review of 38 children with neurological symptoms of vitamin B12 deficiency, all recovered within one month of B12 supplementation; fatigue was among the symptoms but was not reported separately.Neurological symptoms of vitamin B12 deficiency: analysis of pediatric patients.
- In a study of 37 adults with pulmonary arterial hypertension, 29% had a functional vitamin B12 deficiency, but no supplement was tested, so the study does not show whether B12 improves energy.Nutritional status in pulmonary arterial hypertension.
- People with chronic fatigue syndrome had lower functional vitamin B6 status than matched healthy controls, based on lower activity of the vitamin-dependent enzyme aspartate aminotransferase in red blood cells.Vitamin B status in patients with chronic fatigue syndrome.
- In a small case series of 20 infants with vitamin B12 deficiency, who were treated with cyanocobalamin, clinical and lab findings improved overall, though energy was not separately reported and the dose and duration were not stated.Vitamin B12 Deficiency in Infants.
- In four adults with hypophosphatasia given empirical pyridoxine therapy, symptoms such as fatigue were not relieved.Hypophosphatasia in Adults: Clinical Spectrum and Its Association With Genetics and Metabolic Substrates.
- All 5 people with ALS who received methylcobalamin injections reported more energy and less fatigue, based on interviews; the dose was not stated.Patients' experiences with methylcobalamin injections in amyotrophic lateral sclerosis.
- In lymphoma survivors, a higher marker of vitamin B6 breakdown was associated with a greater risk of chronic cancer-related fatigue.Metabolic analysis of amino acids and vitamin B6 pathways in lymphoma survivors with cancer related chronic fatigue.
- This survey of hypothetical scenarios found people kept taking B12 for fatigue after a small symptom improvement, showing post hoc bias rather than any real effect of B12 on energy.Post Hoc Bias in Treatment Decisions.
- In five people with a genetic nerve disorder, supplementing pyridoxal 5'-phosphate normalized blood levels and improved fatigue, power and pain, and in one family the patients regained the ability to walk independently.PDXK mutations cause polyneuropathy responsive to pyridoxal 5'-phosphate supplementation.
Review Totals and Summary
Members Only41 reviews
Feedback I could verify for this specific product is limited, mostly the 45 reviews on the Dirobi retailer page, and the themes below should be read with that in mind. Customers most often praise the taste. They describe the berry flavor as pleasant and "more than bearable," which matters because many liquid B vitamins taste medicinal. The second theme is convenience. Buyers like that the spray is easy to use, needs no swallowing, and fits into a morning routine. The third theme is perceived energy and focus. Reviewers report better energy, mental clarity and stamina, and some say the effect is noticeable and not jittery. One buyer who first liked the spray for its taste said they also lost weight while using it, though that is an individual anecdote and not a typical result. Several shoppers say the value is good, and they describe reordering because the product feels worth the money. Complaints about this product were hard to find. Reviews on CCL's other sprays and on competing B12 sprays show concerns that may apply here as well. Some buyers question whether the formula uses the methylcobalamin form they want and whether the "nano" absorption claims are real. A few report that sprays can be too sweet or leave an aftertaste. Others report that fast-acting stimulants, including supplements in this category, trigger jitteriness or anxiety in sensitive people. One reviewer of CCL's glutathione spray said it caused panic symptoms. That is a different product, but it shows that CCL's sprays do not suit everyone. Reviews also mix up energy effects that could be placebo with real correction of a deficiency. People who were actually deficient tend to report the clearest benefit, and people with normal B12 levels report subtle or no change. Overall, the picture is of an enjoyable, easy-to-use B12 spray with a good taste and enough reported energy benefit to bring repeat buyers. The marketing claims about absorption speed and nanotechnology are not backed by independent evidence in the reviews I found.
Biohacker Summary
Members Only10 of 10 recommend it
Folic acid, the main ingredient, gets a mostly cautious reaction from the panel: five of the ten warn against it, mainly because it is synthetic, the body may not convert it well, and it may cause problems for people with the MTHFR gene variant. Three panelists recommend it, but only in the context of pregnancy, either for anyone trying to conceive or through a prenatal vitamin, and one of them suggests pairing it with methyl folate. One of the warning voices still says to take folic acid if drinking green tea during pregnancy, and one panelist only discusses the difference between folate and folic acid when choosing prenatal vitamins. Vitamin B12 is a smaller ingredient in this product, and panelists who mention it favor the methylcobalamin form, with some suggesting a sublingual form or a time of day away from bedtime. Vitamin B6 is also a smaller ingredient in this product, and views on it split between those who favor the active form and one who avoids it over nerve damage concerns.
See all 10 biohackers →Hide the biohackers
Ben Greenfield · Folic Acid · warns
- Warns that folic acid is an inactive form of folate that the body cannot efficiently convert, meaning one won't get the full benefit.
- Noted that too much folic acid doesn't necessarily help her due to her MTHFR gene.
- Recommends getting vitamin B12 tested and supplementing if deficient, as B12 deficiency can cause damage to the myelin coating around nerves, including cochlear nerves, and improve tinnitus severity scores.
- Would refine the guidelines to include clearer distinctions between synthetic folic acid and natural folate.
- Warns that folic acid is an entirely man-made chemical that does not occur naturally and is not recognized by the body.
- Recommends Vitamin B6 for the conversion of tryptophan to serotonin and then melatonin in the pineal gland.
- He recommends Vitamin B12, especially for kids on a vegan or vegetarian diet, as it is essential for nervous system development.
- Mentions that blood testing for an energy crisis would include nutritional things like a vitamin B12 level.
- Ben Greenfield consumes vitamin B12 as part of the Update Energy Drink.
- Ben clarifies that synthetic folic acid found in fortified cereals, grains, and energy drinks is more of a concern than natural forms of methylfolate for those with the MTHFR gene.
- Ben warns against synthetic sources of folic acid, especially for poor methylators, as it can lead to homocysteine buildup and inflammation.
- Ben warns that if you are taking a multivitamin or cereal fortified with folic acid, it could do more harm than good, noting that folic acid is an entirely man-made chemical not found naturally.
- Is warned that if he is a poor methylator, folic acid, found in many energy drinks, supplements, and enriched foods, can cause an inflammatory reaction, homocysteine buildup, and sometimes CRP buildup.
- Warns against synthetic folic acid, found in energy drinks, bars, and poorly formulated multivitamins, especially for poor methylators, as it can lead to a buildup of inflammatory homocysteine, accelerating brain aging.
Thomas DeLauer · Folic Acid · warns
- Warns that synthetic folic acid supplements may not convert effectively in many people due to a gene variant, potentially blocking cellular folate uptake and masking B12 deficiencies.
- Recommends Vitamin B12 for mental health and mood, explaining its role in myelination and neurotransmitter production. They specifically recommend a liposomal and micellar form of methylcobalamin B12 for better absorption and to avoid toxicity.
- Mentions that a single serving of sardines provides vitamin B12 at something like three to four times the daily needs.
- Recommends taking methylcobalamin as a methylated form of B vitamin for mitochondrial function.
- Recommends ensuring adequate vitamin B6 intake, as it is a required cofactor for cells to use absorbed magnesium and improves central nervous system relaxation when combined with magnesium.
- Recommends vitamin B6 to support GABA production and find balance for mental clarity.
- Mentions B12 as a critical B vitamin for reducing homocysteine.
- Advises against taking vitamin B12 if one's diet already provides enough, suggesting a B complex or liver capsule instead for B vitamins.
- Was taking Vitamin B12 with fat burner injections, which he later stopped cold turkey, leading to a period of intense emotional and hormonal imbalance.
- Warns that high levels of supplemental vitamin B12 are a risk factor for insomnia, as it is an energy-building supplement, and advises taking it in the morning or lowering the dose.
- Notes that depending on one's diet, adding a good multivitamin might be beneficial, specifically recommending a methylated multivitamin for better absorption and utilization.
- Notes that depending on one's diet, adding a good multivitamin might be beneficial, specifically recommending a methylated multivitamin for better absorption and utilization.
- Says his kids love taking Hiya multivitamins because they are sweetened with monk fruit and have no sugar, making it a fun ritual for them.
- Uses Create's Daily Performance Gummy, which contains a multivitamin, a low dose of creatine, adaptogenic mushrooms, and greens, and also adds a separate creatine gummy later in the day.
Dr. Rhonda Patrick · Folic Acid · recommends
- Recommends a combination of methyl folate and folic acid, as folic acid has been shown to reduce neural tube defects.
- Warns that Vitamin B12 enhances light's melatonin-suppressing effects and should be avoided too close to bedtime.
- Notes that a med can cause vitamin B12 deficiency, especially as absorption decreases with age, and suggests a sublingual form or B12 injections for older individuals.
- Discusses the origin of Vitamin B12, suggesting it's a microorganism that propagates in the soil and that animals get it from eating dirt, which is why it's less available in modern, sanitized plant foods.
- Mentions that a scientist showed that a lack of folic acid in mice and people can cause chromosomes to break, similar to radiation damage. She notes that 10% of the U.S. population and half of the poor have levels below this threshold.
- Dr. Patrick states that people with a specific gene polymorphism in the NPF3 gene, which affects vitamin B6 levels, may need to increase their dietary intake of B6 and/or supplement with vitamin B6.
- Vitamin B6 can suppress the production of Advanced Glycation End products.
- Describes a study where female mice fed a diet high in B vitamins, folic acid, and vitamin B12 three weeks before pregnancy had offspring that no longer had yellow fur and were not predisposed to obesity and cancer.
- Describes a study where female mice fed a diet high in B vitamins, folic acid, and vitamin B12 three weeks before pregnancy had offspring that no longer had yellow fur and were not predisposed to obesity and cancer.
- Dr. Patrick warns that giving excessive levels of folic acid to individuals already in an early or late stage of cancer can actually accelerate the cancer.
- Dr. Rhonda Patrick discusses folic acid vs. folate.
- Folic acid is needed to build new DNA in the absence of cancer, but it can be problematic if cancer is present because cancer cells are highly proliferative and also need it to produce DNA.
- Folic acid supplementation appeared to reduce the harmful effects of lead exposure.
- Describes a study where female mice fed a diet high in B vitamins, folic acid, and vitamin B12 had offspring that silenced a gene predisposing them to obesity and cancer.
Dr. Eric Berg · Folic Acid · warns
- Warns that folic acid can build up in the blood for people with an MTHFR gene alteration, leading to an increased risk of cancer and a suppressed immune system.
- Dr. Berg lists pyridoxine hydrochloride as a synthetic vitamin to avoid.
- Recommends taking the active form of vitamin B6, pyridoxal-5-phosphate (P5P), for its benefits to the nervous system, including building the myelin sheath and protecting sensory nerve integrity.
- Notes that Vitamin B6 is intimately involved in the nervous system and may be behind sciatica and carpal tunnel syndrome.
- Recommends taking the natural form of vitamin B12, methylcobalamin, to support nerve regeneration, myelin production, and nerve growth factors.
- Notes that Vitamin B12 is intimately involved in the nervous system and may be behind sciatica and carpal tunnel syndrome.
- Recommends taking vitamin B12 if on a med.
- States that high vitamin B6 levels can be linked to peripheral neuropathy.
- Briefly mentions Vitamin B12 in relation to neuropathy.
- States that vertical ridges on nails could mean a vitamin B12 deficiency, and slightly brown or grey nails, especially for vegans, could indicate low B12. Completely white nails with a pink strip across the top could also be low B12.
- Recommends incorporating vitamin B12 foods into the diet, especially for those who don't regularly consume animal products, to prevent irreversible damage to the nervous system.
- Dr. Berg mentions that fermented dairy contains vital nutrients, including vitamin B12.
- A vitamin B12 deficiency can cause irreversible damage to your nervous system, so it's important to prioritize acidifying your stomach as you age.
- States that Vitamin B12 is crucial for health and many people are deficient without realizing it.
Dave Asprey · Folic Acid · warns
- Warns that folic acid is not the same as folate and that the body processes them differently.
- States that Vitamin B12 is extremely important for every kind of brain function and recommends ensuring B12 levels are optimal, around 500, not just barely above normal.
- Warns against folic acid, stating it is synthetic and can cause inflammation, especially for individuals with MTHFR alleles, and that almost everyone on it needs to stop.
- Recommends taking folic acid if consuming green tea during pregnancy, as green tea depletes it.
- Warns that folic acid, an industrial form of B vitamin not found in nature, is toxic to 30-40% of people and not very beneficial for the rest, criticizing its addition to grain in the US.
- Mentions Vitamin B6 as playing a role in methylation pathways.
- States that folinic acid, a different form of folic acid, is being found to make autism symptoms go away in people, as it bypasses methylation issues better than methylfolate.
- Recommends taking vitamin B12 if one has a deficiency.
- Mentions having a problem with folic acid, as predicted in his first book.
- Warns against taking folic acid, especially if pregnant, stating it is a man-made chemical that does not exist naturally and can be poisonous for individuals with MTHFR deficiencies.
- Warns that the synthetic form of vitamin B6 found in almost all multivitamins and energy drinks binds to B6 receptors for a thousand days, making them unavailable for the beneficial form.
- States that folic acid is toxic for about a third of people, including themselves, due to MTHFR genes, and criticizes the government for mandating its inclusion in food.
- Dave Asprey notes that it's almost impossible to get vitamin B12 in a vegan diet, and it's primarily found in animal meat.
- Says they would take a bunch of their Wild Lights Vitamin B6 if they had to eat almonds, to try and pass them.
Andrew Huberman · Folic Acid · recommends
- Recommends taking a prenatal vitamin that has folic acid before getting pregnant to optimize nutrients for pregnancy.
- States that a deficiency in vitamin B12 can be terrible and lead to chronic fatigue-like syndromes, as many parts of mitochondria require B vitamins.
- Recommends taking methyl B12 as part of methylated B vitamins to lower homocysteine levels and reduce cardiovascular risk.
- Has been taking AG1 for over 10 years, once and often twice every day, to ensure he gets all necessary vitamins, minerals, probiotics, and adaptogens, considering it a nutritional insurance policy.
- Does not supplement B6 due to evidence that overs-supplementing vitamin B, especially B6, is problematic because of peripheral nerve damage.
- Agrees with a dermatologist's recommendation for people to get enough folic acid due to its role in DNA synthesis and repair of skin cells.
- Has been taking AG1 since 2012 to ensure he gets enough vitamins, minerals, Prebiotic fiber, and other nutrients typically found in fruits and vegetables, providing nutritional insurance.
- States that folic acid is important to prevent neural tube defects and in cell division, and recommends that women and men take a vitamin with folic acid even when not trying to conceive.
- Andrew Huberman started drinking AG1 in 2012 and still drinks it once or twice a day because it provides all his foundational nutritional needs, ensuring proper amounts of vitamins, minerals, probiotics, and fiber for optimal mental health, physical health, and performance.
- Notes that some people are exploring the use of P5P, a metabolite of vitamin B6 known to suppress prolactin, as a way to buffer the post-MDMA crash, though there are no human data yet.
- Recommends the consumption of B12 and other B vitamins, especially folate, as it has been shown to partially decrease cancer risk in people who ingest alcohol, though it does not completely offset it.
- Started taking AG1 in 2012 and still takes it once or twice a day because it covers foundational vitamin, mineral, and probiotic needs, and supports immune system function and a healthy gut microbiome.
- Recommends P5P, which is vitamin B6, as a dopamine agonist to help with low drive and motivation.
- He has been using Athletic Greens for over a decade to cover his vitamin and mineral bases and support his gut microbiome, immune system, gut-brain axis, and mental functions.
Dr. Mark Hyman · Folic Acid · neutral
- Discusses the difference between folate and folic acid when choosing prenatal vitamins.
- Optimized a child's nutrient status with vitamin B6, as the child had low B6 levels.
- States that vitamin B12 is a nutritional deficiency that impacts mental health.
- Recommends vitamin B6 with folate and B12 as supplements with strong evidence for PMS.
- Recommends vitamin B12 with vitamin B6 and folate as supplements with strong evidence for PMS.
- Believes that if functional testing is done to replete deficiencies like vitamin D and B12 before someone stops their medication, withdrawal symptoms can be completely eliminated.
- Mentions that repletion of vitamin B12 can help safely withdraw someone from meds and that simple vitamin B12 deficiencies are important to address in a depression workup.
- Lists Vitamin B12 as important for nerve health and energy.
- Warns against folic acid, stating that 44% of the population cannot process it, it is not a natural nutrient, and it should be avoided, especially by those with the MTHFR gene.
- Mentions vitamin B12 as a core nutrient required for methylation, noting that deficiencies can lead to various health issues.
- Recommends supplementing with Vitamin B12 for hair follicle health and growth, especially for vegans, as many people are deficient.
- Recommends checking vitamin B12 levels as a first step before taking any supplements.
- Warns that meds (meds) block the absorption of vitamin B12, which requires stomach acid to be absorbed. Long-term B12 deficiency can lead to depression, neurological problems, and dementia.
- States that Vitamin B6, at 50 to 100, is important for estrogen metabolism.
Peter Attia · Folic Acid · recommends
- States that folic acid is important for anyone trying to get pregnant.
- Notes that deficiencies in certain vitamins and minerals, such as B12, can be a cause of hair loss in women.
- Explains that when a person is not responding to traditional B vitamins, they will step it up and give them methylcobalamin B12.
- Notes that Ryan Lochte was suspended for a doping rule violation after a social media post showed him taking vitamin B12 in an illegal way, by IV infusion.
Siim Land · Vitamin B12 · uses
- Created Microvitamin, a supplement that bundled all the supplements he was taking, to help fund his a med trial.
- States that vitamin B12 deficiency is the most common reason for premature graying of hair and recommends fixing B12 status if it is deficient, as it gives a greater likelihood of reversing gray hair.
- Mentions that insufficient vitamin B6 can raise prolactin levels.
- Recommends B12 for vegans, noting it is a standard vitamin found in animal products.
- Is experimenting with serine plus vitamin B6 to impact homocysteine levels, a mechanistic hypothesis he is testing.
- Takes 1 gram of Vitamin B12 from DoNotAge in the morning for longevity.
- Takes 1 gram of Vitamin B6 from DoNotAge in the morning for longevity.
- Mentions Vitamin B12 as a key nutrient involved in the methylation cycle that helps prevent methionine from raising homocysteine levels.
- Explains that one can store up to 30 years' worth of vitamin B12 if they get a lot of it, particularly from superfoods like clams, liver, and oysters, but most people are not in that position.
- Mentions vitamin B6 as another example where the principle of metabolic conversions from plant to animal forms applies, with genetic variations affecting the ability to get B6 from plant foods.
Bryan Johnson · Vitamin B12 · uses
- States that Blueprint essential capsules and soft gels are packed with key vitamins and minerals needed for strong bone health.
RAL Summary
Members OnlyTier 4 for Energy
Folic acid has some mixed human support for fatigue, mostly from combination products [5], while the B12 and B6 trials largely found no energy benefit [1][8]. No reviews were counted to confirm a benefit, so the evidence stays emerging.
- Emerging: not enough evidence to rank higher yet.
Where the evidence disagrees: 31 of the 48 human studies found no effect.
More Details
Members OnlyBody systems · Combine with · Possible side effects
Body systems: Nervous system, Blood, Metabolism
Combine with: For energy and nervous system support, methylcobalamin pairs well with methylfolate (B9) and vitamin B6 (P-5-P) for methylation and homocysteine metabolism, plus iron (if deficient), magnesium, CoQ10, and a B-complex for broader energy metabolism. Vitamin D3/K2 and omega-3s can support general health. If the real goal is fast heartburn relief, use a separate product such as calcium carbonate antacid, sodium alginate, or magnesium hydroxide, and consider B12 if you use acid-reducing medications long term, since they may impair B12 absorption. Consult a healthcare provider about persistent heartburn.
Possible side effects: No major side effects were reported in the studies. A large trial of low-dose B vitamins saw slightly more activity limits from emotional problems, and a high-dose B complex group reported worse sleep and more tiredness on waking. Reviews of similar sprays mention a sweet aftertaste and jitteriness in some people.
Supplement Facts
Pyridoxine Hydrochloride 2 mg · Folic Acid 800 mcg · Vitamin B12 1000 mcg
| Pyridoxine Hydrochloride | 2 mg | † |
| Folic Acid | 800 mcg | |
| Vitamin B12 | 1,000 mcg |
Other ingredients: Purified Water, Glycerine, Berry flavor, Xylitol, Citric Acid, Potassium Sorbate, Benzyl Alcohol.
Directions: Directions: Daily dose: Take 6 sprays by mouth. Advanced dose: Take 6 sprays by mouth, twice daily. Spray, swish and swallow. Do not eat or drink for 2 minutes following. Take as recommended by your physician.
Barcode (UPC) 08599340061960 · Label source: NIH label database · Report a label change
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Our articles on this subject
- Folate vs Folic Acid: What the Studies Show About Each FormArticle · Oct 29, 2026
- Best Vitamins for Fatigue and the Habits That Matter MoreArticle · Jun 15, 2026
Graded November 7, 2026 by the Reverse Age Lab evidence engine, from human studies, real reviews and our biohacker panel. How we grade. Is this medical advice? No. Rala organizes the published evidence; go over any change with your doctor, especially if you take meds.
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