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Product Review: B Vitamin Supplements and Energy Drinks (Including B Complexes, Niacin, B-6, B-12, Biotin, Thiamin, and Folic Acid)
 

Posted: 9/6/14  Last Update: 1/10/17
B Vitamins and Energy Drinks Reviewed by ConsumerLab.com Sections: Jump to a section by clicking on its name.

Background:
B Vitamins
There are eight B vitamins generally known as thiamin (B-1), riboflavin (B-2), niacin (B-3), pantothenic acid (B-5), pyridoxine (B-6), biotin (B-7), folate (folic acid, B-9), and cobalamin (B-12). Like most vitamins, B vitamins are essential -- your body needs them but cannot make them; you must get them from your diet or from supplements.

Each B vitamin is associated with a variety of functions, many of which relate to turning food into energy and other needed substances. There are also potential toxicities when getting too much of certain B vitamins. Folate, for example, is important in reducing birth defects of the spinal cord and is, therefore, a critical ingredient in prenatal vitamins. But at a high dosage, folic acid may increase the risk of certain cancers. Niacin, when taken in very high doses, can improve cholesterol levels but can also cause side-effects (such as skin flushing) and liver toxicity.

Combinations of B-6, B-12, and folate have been shown to reduce elevated homocysteine levels -- a risk factor for cardiovascular disease, although studies have not shown this combination to reduce cardiovascular risk itself. A review of 14 studies involving B vitamin supplementation found that reduced levels of homocysteine attributable to B vitamin supplements was associated with a slight (7%) reduction in the risk of stroke. However, there was no reduction in stroke directly associated with the use of B vitamins (Ji, Neurology 2013). Nevertheless, for people who are deficient in vitamin B-9 (folate), supplementing with folic acid may significantly reduce the risk of stroke (See Folate below).  

Certain B vitamins, or combinations, may also help slow declines in memory and cognition when taken long-term (at least 18 months), according to several studies. In a 2-year placebo-controlled study of people aged 70 years or older with mild cognitive impairment, a combination of B vitamins was found to slow cognitive decline, particularly in those who started with elevated levels of plasma homocysteine (over 11.3 micromoles/L) - which can occur with inadequate B-vitamin intake. People in the study were given a daily dose of folic acid (800 mcg), vitamin B-12 (500 mcg), and vitamin B-6 (20 mg) (de Jager, Int J Geriatr Psy 2011).
Further analyses of this study found that the beneficial effects of B vitamins were enhanced when people began the study with blood plasma levels of omega-3 fatty acids in the upper range of normal, In fact, those with low omega-3 levels did not benefit from B vitamin supplementation. In general, the effects were more significant for DHA alone than for EPA the combined levels (Oulhaj, J Alz Dis 2016).

In a similar study, this same B vitamin combination reduced the amount of shrinkage in regions of the brain commonly affected by Alzheimer's disease. The benefit was found only among people who started the 2-year study with high homocysteine levels (over 11.06 micromoles/L), but this represented about 50% of the people in the study. Shrinkage was reduced by 8 times compared to the amount of brain shrinkage experienced among those taking placebo (Douaud, PNAS 2013).
As with the research noted above by Oulhaj, further analysis of this study also found that higher blood levels of omega-3 fatty acids enhanced the beneficial effect of the B vitamins (Jerneren, Am J Clin Nutr 2015).

Cognitive benefits were also seen in a study that used smaller daily doses of just folic acid (400 mcg) and B-12 (100 mcg -- which is still many times the daily requirement). In that study (Walker, Am J Clin Nutr 2012), adults aged 60 to 74 years with depressive symptoms received the vitamins or placebo in two daily oral doses. Compared to placebo, there were small but significant improvements in short and long-term memory. Improvement was seen after 2 years -- but not after 1 year. The researchers concluded that the vitamin combination is a potentially effective long-term intervention for minimizing cognitive decline. The role of B-12 specifically in minimizing cognitive decline is suggested by a study which, after following several hundred people in their 70's over an eight-year period, found that cognitive decline was faster among those with the lowest blood levels of B-12 (under 257 pmol/L) -- a group representing 40% of those in the study (Morris, J Am Geriatr Soc 2012). Normally, people are not considered B-12 deficient (and at risk for pernicious anemia) until levels go below about 148 pmol/L (200 pg/mL). The study suggests that it may be beneficial to maintain somewhat higher levels of B-12. As noted in the B-12 discussion below, it is already medically recommended that people over age 50 get at least 2.4 mcg of B-12 daily from supplements or foods fortified with B-12. Similarly, a large placebo-controlled study in Holland of adults 65 and older suggested that blood levels of B-12, particularly in its active form, holo-transcobalamin, may indicate who can most benefit from supplementing with B-vitamins. In this study, all participants had high homocysteine levels (12 to 50 micromol/L) although many were not actually deficient in B-12 (the mean level was 257 pmol/L). After being given folic acid (400 mcg) and B-12 (500 mcg) daily for 2 years, compared to placebo, there was only a possible minor slowing in the decline in cognitive functioning. However, those who started the study with lower levels of holo-transcobalamin (below 64 pmol/L) had more benefit from supplementation in terms of episodic memory performance (i.e., recall and recognition) and information processing speed (van der Zwaluw, Neurology 2014). In this study, both the treated and placebo groups received 600 IU of vitamin D3 daily due to a high percentage of deficiency (44%) in the population.

In summary, if your B-12 levels are somewhat low, taking B-12 (100 mcg to 500 mcg) and, possibly, folic acid (400 mcg), each day, may help slow age-related declines in memory and cognition.

Deficiency in B-3 (niacin), B-6, and/or B-12 can cause depression (as well as other symptoms) (Kennedy, Nutrients 2016; NIH 2016). Higher intakes of B-6 and B-12 from supplements are associated with a lower likelihood of depression in older adults (Skarupski, Am J Clin Nutr 2010) and having higher blood levels of B-12 is associated with a higher probability that SSRI medication will help one recover from major depression (Hintikka, BMC Psych 2003). B-12 injections (1,000 mcg per week) taken with tricyclic antidepressants or SSRIs may improve symptoms of depression in people with low-normal blood levels of vitamin B-12 (190 pg/ml to 300 pg/ml) more than medication alone (Syed, Open Neurol 2013). Treatment with B-6 found to help women deficient in B-6 who had depression associated with use or oral contraceptives, but it has generally not helped other people suffering from depression (Williams, Family Practice 2005).

Folate may have a potential role in treating depression when used along with other treatments (Taylor, J Psychopharmacol 2004) For example, a daily dose of 500 mcg of folic acid was shown to increase the effectiveness of the SSRI drug fluoxetine (Prozac) in women (but not men), increasing the recovery rate from depression by 25% compared to treatment with Prozac alone (Coppen, J Affect Disord 2000).

In general though, supplementation with B-6, B-12 and/or folate has not been found to reduce the incidence of depression or improve mood in people who are not deficient in these vitamins (Ford, J Clin Psychiatry 2008; Bryan, J Nutr 2002).

People with recurrent aphthous stomatitis (canker sores) may have low dietary intake or deficiency in B-12 and/or folate (Kozlack, J Oral Pathol Med 2010; Preeti, J Oral Maxillofac Pathol 2011). A small study suggested that vitamin B-12 supplementation may help to reduce canker sores even in people who are not deficient in B-12. It found that among 52 adults with recurrent canker sores, most of whom were not deficient in B-12 (≥ 184.5 pmol/L), a sublingual tablet providing 1,000 mcg of vitamin B-12 (Solgar) taken once daily before bedtime for six months decreased the number of canker sores, pain levels, and duration of outbreaks compared to placebo; more than 74% of those who took vitamin B-12 were canker sore-free after six months compared to 32% of those who took a placebo (Volkov, J Am Board Fam Med 2009).

Benfotiamine, a derivative of thiamin (B-1), may, according to preliminary research, help alleviate neuropathic pain in people with diabetes when taken at a daily dose of 400 mg (two 50 mg tablets four times daily) (Haupt, Int J Clin Pharmacol Ther 2005). 

For more information on uses, doses, safety concerns, and food sources for each of the B vitamins, see the ConsumerTips™ section or use the links below.

Energy Drinks & Shots:
Energy drinks and shot-sized drinks have become hugely popular although, in many cases, they don't deliver much real energy (i.e., calories). What they do deliver is stimulation, due to their significant caffeine content (more on that, later). They also tend to contain B vitamins -- often much more than you need or want. Why the B vitamins? Probably to play on the fact that B vitamins help convert food to energy. However, since few people are deficient in B vitamins, these added vitamins are likely to provide no benefit and may put you at risk for exceeding Upper Tolerable Intake Levels (ULs) for these vitamins — levels above which there is increasing risk of toxicity. These ULs are based on your total daily intake of each vitamin (including other supplements and fortified foods, like breakfast cereals and energy bars). In the What CL Found section, you'll see how close to these ULs some of these products can put you. You can find the ULs for B vitamins in the ConsumerTips section.

Quality Concerns and What CL Tested For:
Previous reviews by ConsumerLab.com have uncovered problems with the B vitamin content of several supplements. Neither the U.S. government nor any agency is responsible for routinely testing B vitamin products or other dietary supplements for their contents or quality.

ConsumerLab.com, as part of its mission to independently evaluate products that affect health, wellness, and nutrition, purchased dietary supplements sold in the U.S. and Canada claiming to contain single B vitamins or B vitamin complexes. These products were tested to see if they contained their claimed amounts of the eight B vitamins. Products sold as regular tablets or caplets were also tested for their ability to break apart properly for absorption. In addition, products were evaluated to determine if their suggested daily dose exceeded Tolerable Upper Intake Levels (ULs) for B vitamins as established by the Institute of Medicine of the National Academies. See How Products were Evaluated for more details about the testing.

Energy drinks and shots were additionally tested for their caffeine content.

What CL Found:
Testing revealed problems with 3 out of 26 B vitamin supplements selected by ConsumerLab.com for review, and with 3 out of 4 of the "energy" drinks . All of the products that failed contained combinations of B vitamins as "complexes" or were energy products; none were single B vitamin supplements. Products failed testing for reasons described below. These deficiencies were confirmed in a second independent laboratory. Twenty-three (23) products passed testing, as did 11 products similarly tested through ConsumerLab.com's voluntary Quality Certification Program.

B-Complexes:

  • MegaFood Vegan B12 contained 180% of its listed amount of folate (720 mcg per tablet, rather than 400 mcg). It did, however, contain its listed amount of vitamins B-6 and B-12.
     
  • Nutrilite Natural B Complex contained much more folic acid (210%) than claimed. ConsumerLab.com discovered a similar problem when it tested samples of this product in 2012, finding 229.5% of the listed amount of folic acid. While it is acceptable practice for vitamin manufacturers to put in modest "overages" of ingredients to ensure that they will have at least 100% of their listed nutrients up to their expiration dates (October 2015, in this case), the overage amount of folic acid in this product is unusually high. In fact, the amount of folic acid in the suggested 3 tablet daily serving of this Nutrilite product is 840 mcg — near the daily upper limit for the folic acid form of folate for adults (1,000 mcg) and more than twice the daily requirement (400 mcg). Taking this product along with just a bowl of fortified cereal providing more than 40% of the Daily Value (DV) for folate, for example, will put you at increased risk for toxicity (See Folate, Upper Limit below) and may increase the risk of certain precancerous tumors becoming malignant.
     
  • Nutrition Now B Complex contained 228% and 169.3%, respectively, of its listed amounts, of pantothenic acid and biotin, although it did contain the listed amounts of other B vitamins. Although it could not be "Approved," pantothenic acid and and biotin are very safe even at these levels and no UL has been established for either vitamin.
Among the B-complexes that passed review, it is difficult to say which, if any, is "best," as that depends on which B vitamins you are seeking, their respective amounts, and the forms of these B vitamins. The formulas for these products are very different, as shown in the table below. It is safe to say, however, that you need not spend more than about 10 to 25 cents per day to get a good quality product. To help you compare the amounts of B vitamins in these supplements to the daily requirements refer to the amounts listed for each vitamin at the top of the table. Be aware that one of the B-complexes, GNC B-Complex + Energy, includes a significant amount of caffeine (100 mg/capsule), which may cause a stimulant effect (see more about caffeine in the Energy Drinks and Shots section).

Single B Vitamins
All products containing single B vitamins (i.e., niacin, B-6, B-12, biotin, folate, or pantothenic acid) contained their listed amounts of these vitamins. The following information may help compare them:

Niacin supplements -- Be aware that the recommended doses of all the niacin-only products and some of the B complex products exceeded established Tolerable Upper Intake Levels (ULs) for adults for niacin, above which there is increased risk of side effects with regular use. The adult UL for niacin is 35 mg per day. Doses much higher than the ULs are used medically to improve cholesterol levels. However, high doses of niacin can cause dangerous liver inflammation. For this reason, regular lab tests and the supervision of a healthcare professional are strongly advised before taking niacin at doses above the ULs. Also note that the forms of niacin vary in their use and side effects: nicotinic acid in high doses can lower cholesterol levels but can cause flushing of the skin; niacinamide does not cause flushing but does not improve cholesterol levels. A product containing nicotinic acid, Slo-Niacin, is a delayed-release tablet that may reduce the risk of skin flushing. See the ConsumerTips section on Niacin for more information. The lowest cost per milligram of niacin from an Approved product was from NOW Niacinamide as well as Solaray Niacin
B-6 Supplements — These supplements provided very different amounts of vitamin B-6, ranging from 50 to 250 mg, all of which are far higher than the daily requirement (about 2 mg). Klaire Labs Vitamin B6 offered the lowest cost per mg of B-6 (11 cents for 250 mg). However, be aware that this dose exceeds the UL for B-6 (100 mg) and should only be used if you are known to be deficient. The other two products also provided large amounts of B-6 compared to the daily requirement, but did not exceed the UL and are modestly priced at 6 cents for 50 mg (Country Life) and 7 cents for 100 mg (Nature's Plus).

B-12 supplements — All of the products are designed to provide far more than the daily requirement of B-12 (2.4 mcg) -- in fact, when selecting products to test, we could not find any marketed supplements (other than B-complexes) which provide only the dialy requirement for B-12. Instead, these products provide hundreds of micrograms of B-12. While this may only be necessary if you are deficient in B-12 (in which case you'll want at least 500 mcg per day), these amounts are considered safe --  there is no established upper limit (UL) for B-12. The least expensive product per microgram of B-12 was Spring Valley (Walmart) B-12 microlozenge (7 cents per 2,500 mcg lozenge). Most other B-12 products were also just a few cents a day. Although there are many orally-dissolving, sublingual, or spray B-12 products, B-12 will get absorbed just as well as from a tablet, as shown in a clinical trial (Sharabi, Br J Clin Pharmacol 2003). Most of the supplements provide B-12 in cyanocobalamin form. Some people are concerned about the cyanide component of this form, but there is little scientific rationale for this concern. If you still want to avoid cyanocobalamin, use the Natural Factors B12 (12 cents per 1,200 mg chewable tablet) or Dr. Mercola Vitamin B-12 spray (10 cents per 167 mg spray), both of which are made with methylcobalamin.

Biotin supplements — Each of the products contains far more than the daily requirement for biotin (30 mcg) but are safe — there is no UL for biotin. The lowest cost for obtaining biotin is from Vitacost Quickdot Chewables (10 cents for 3,000 mcg from 2 chewables), while Nature's Life Biotin is close in price (9 cents per 2,500 mcg capsule).  Nature's Life Biotin is called a "Hair, Skin and Nails Formula" because the dose of 2,500 mcg is the daily amount of biotin which was used in a small study that showed an increase in nail thickness and a reduced tendency for split nails (see ConsumerTips for biotin).

Folate (folic acid) supplements — While few people in the U.S. need folate supplementation due to the fortification of grain products, women capable of becoming pregnant women are advised to get 400 mcg daily from a supplement — as found in Finest Nutrition (Walgreens) Folic Acid and Rite Aid Folic Acid, each of which cost just 2 cents per tablet. Higher amounts, as in Whole Foods Folic Acid which contains 800 mcg per tablet, are generally needed only if you are known to be deficient in folate. (See ConsumerTips for Folate.) Jarrow and Thorne provide, at several times the cost, another form of folate, methylfolate. As discussed in more detail below, methyl folate may offer modest advantages in certain situations.

Pantothenic acid supplements — This is not a popular category, as deficiency is rare. Only one product was tested and Approved, Nature's Way Pantothenic Acid. This product also contains a small amount of calcium (46 mg) due to the chemical form of the vitamin -- D-calcium pantothenate. (See ConsumerTips for Pantothenic Acid).

Energy Drinks and Shots:
Among four popular energy drinks/shots/squirts selected by ConsumerLab.com for review, each contained the amount of caffeine indicated the label, ranging per serving from 60 mg in a 2.5 mL (½ teaspoon) squirt of MioEnergy Liquid Enhancer to 221 mg in a 57 mL shot-sized bottle of 5-Hour Energy. (For reference, the amount of caffeine in a cup of regular brewed coffee averages 95 mg, according to the USDA (USDA National Nutrient Database 2012). In addition, one of the B vitamin pills, GNC B-Complex + Energy (listed in first table, below) also contained its listed 100 mg of caffeine per capsule. However, the following three products did not contain their listed amounts of each B vitamin.
  • 5-Hour Energy (Berry) contained only 72.3% of its claimed of vitamin B-12, providing 361.4 mcg per bottle, but contained its listed amounts of niacin, B-6, and folic acid. The product label suggests drinking half a bottle to 2 bottles per day. At the higher amount, one would ingest 60 mg of niacin, which is in excess of the upper tolerable limit for niacin (30 mg for those 14 to 18 years old and 35 mg for adults), which is why the product label indicates that you may experience a "Niacin Flush." The amounts of B-6 and B-12 in this product are many times higher than the RDAs for these ingredients, although not exceeding any upper tolerable limit. For young adults, the RDA for B-6 is 1.3 mg and for B-12 is 2.4 mcg, while one bottle provides 40 mg of B-6 (3100% of the RDA) and, as we found, 361.4 mcg of B-12 (15,000% of the RDA).

    5-Hour Energy lists among its ingredients an "energy blend" that includes caffeine. The label notes that the amount of caffeine is comparable to that in a cup of "leading premium coffee." ConsumerLab.com found the 1.93 fluid ounce bottle to contain 221.2 mg of caffeine. However, this is about 23% higher than what you would get from a "short" cup (8 fluid ounces) of a premium coffee such as Starbucks, which Starbucks claims to contain 180 mg of caffeine (Starbucks.com). It is generally advisable not to exceed more than 300 mg of caffeine per day to avoid undesirable side effects, such as jitteriness.
  • MioEnergy Liquid Water Enhancer contained, in a ½ teaspoonful serving, 200% of its listed niacin (yielding 4 mg) and 227.5% of its listed vitamin B-6 (yielding 0.46 mg), while it contained its listed amount of vitamin B-12 (0.6 mcg). Although the amounts of niacin and B-6 were double what was listed, the amounts of these, and B-12, are not of any health concern.
  • Rockstar Zero Carb contained more than double its listed amounts of vitamins B-6 and B-12 and just 70.8% of its claimed pantothenic acid. Although all of these amounts higher than the RDAs, they don't pose a safety concern. Rockstar contained its listed amount of niacin (20 mg per half can), but be aware that drinking a full can would exceed the upper limit for niacin, possibly causing skin flushing.
So should you use energy drinks and shots, and are they safe? If you need something to help you stay alert, any product with caffeine may help. In fact, some clinical studies with Red Bull, which has less caffeine than many other "energy" products (80 mg per 8.4 oz can) demonstrated improved alertness during simulated driving experiences (Reyner, Physiol Behav 2002). A study in male and female competitive athletes found that a caffeinated energy drink given one hour before a training session increased self-perceived muscle power during exercise by 13% compared to a placebo drink which contained the same ingredients - including taurine, sodium bicarbonate, L-carnitine and maltodextrin - but no caffeine (Salinero, Br J Nutr 2014). Additionally, the caffeinated energy drink increased the frequency of insomnia (31.2% vs. 10.4%), nervousness (13.2% vs. 0%) and activeness (16.9% vs. 3.9%) compared to placebo. The caffeinated energy drink contained an amount of caffeine based on each athlete's weight (3 mg per kilogram, working out to about 200 mg for a 150 lb athlete). The authors attributed the effects to the presence of caffeine, and not the other ingredients in the drink. An earlier study using the same caffeinated energy drink and non-caffeinated placebo found the caffeinated energy drink significantly improved athletic performance during a simulated rugby match (Del Coso, Appl Physiol Nutr Metab 2013).

The sugars in Red Bull as well as NOS will also provide some quick energy. It's questionable, though, what all the other ingredients in these products bring to the table (van den Eynde, Tijdschr Psychiatr 2008) and there seems to be no good reason to have to deal with possible skin flush and tingling from all the niacin in just over one bottle of 5-hour Energy or a full bottle of Rockstar -- or potential liver injury from higher intakes. (See the Warning about a case of acute hepatitis associated with excessive niacin intake from energy drinks. Also see the Warning about class action lawsuits against Red Bull for more about energy drinks versus other sources of caffeine).

New research has also raised concern over large amounts of L-carnitine in some energy drinks. Carnitine intake may potentially contribute to cardiovascular disease in certain people. People who eat red meat (as opposed to vegetarians and vegans) maintain organisms in their gut which digest carnitine to the compound TMA, which is then converted in the liver to the compound TMAO which appears to advance atherosclerosis (hardening of the arteries) by reducing the normal clearing of cholesterol (Koeth, Nature Medicine 2013). Using a supplement with L-carnitine may potentially foster growth of these organisms, increase levels of TMAO, and have negative long-term cardiovascular effects.

If you do choose to use any of these "energy" products, it seems best to limit your daily intake and not consume any with high amounts of caffeine all at once. If you use these, avoid other caffeinated products or stimulants. 

It is also important not to mix energy drinks with alcohol. The caffeine can mask the depressant effects of alcohol and lead to dangerous situations in which one may feel or act alert but be mentally compromised. The Centers for Disease Control and Prevention notes that drinkers who consume alcohol mixed with energy drinks are more likely to: binge drink; be taken advantage of sexually; take advantage of someone else sexually; and ride with a driver under the influence of alcohol (CDC Fact Sheet). In addition, it is important to keep energy drinks away from children, as they are more susceptible to the negative effects of cafffeine than adults. In fact, 40% of calls to poison centers from late 2010 to 2013 for "energy drink exposure" involved children under age 6, many of whom were experiencing serious side effects such as abnormal heart rhythm or seizure.

Test Results by Product:
Listed below are the test results for 41 products containing one or more B vitamins. The B vitamin complexes and single B vitamins are in the first table. The second table shows the energy drinks/shots. Products are listed alphabetically within their respective category. ConsumerLab.com selected 30 of the products. Eleven products (each indicated with CL flask icon) were tested at the request of their manufacturers/distributors through CL's Quality Certification Program and are included for having passed testing. Also listed are two products similar to ones that passed but sold under different brand names.

Shown for each product are the labeled amounts of the various B vitamins per pill. Some products may contain other ingredients not shown below, but clicking on "Ingredients" beneath the product name will show a full listing of labeled ingredients. Those products that exceeded recommendations on tolerable upper levels (ULs) for certain ingredients are indicated with an explanatory footnote. Prices paid for each product and the costs per daily serving are shown in the last column.

;

RESULTS OF CONSUMERLAB.COM TESTING OF B VITAMIN SUPPLEMENTS
Click on beneath a product name to find a vendor that sells it.
To find retailers that sell some of the listed products click here.  
Product Name, Serving Size, and Suggested Daily Dose on Label

Click on "Ingredients" for Full Listing  
Claimed Amount of B Vitamins Per Suggested Daily Serving
[Recommended Daily Intake for Adults]
(NL= Not Listed) (mg=milligram; mcg=microgram)  
--TEST RESULTS--
(See How Products Were Evaluated)
Cost for Daily Suggested Serving on Label

Other Notable Ingredients/ Features2

Price Paid
B-1 (Thiamin) (mg)
[1.1 — 1.2 mg]
B-3 (Niacin) (mg)
[14 — 15 mg]
B-6 (Pyrido- xine) (mg)
[1.3 — 1.7 mg]
B-9 Folate (mcg)
[400 mcg]
Inositol (mg) OVERALL RESULTS:

APPROVED or
NOT APPROVED
Contained Labeled Amount of B Vitamins Disinte- grated Proper- ly

(NA = Not Applicable)
B-2 (Ribo- flavin) (mg)
[1.1 — 1.3 mg]
B-5 (Panto- thenic Acid) (mg)
[5 — 6 mg]
B-7 Biotin (mcg)
[30 mcg]
B-12 (mcg)
[2.4 mcg]
B-Complex:
Garden of Life® Vitamin Code® RAW B-Complex™ (2 vegan capsules, once daily) 

Dist. by Garden of Life LLC

Ingredients
5 45
(as niacina- mide)4
10 450
(as folate)
26 APPROVED 3 NA $0.48

Choline, PABA, RAW probiotic & enzyme blend, RAW organic fruit & vegetable blend

Suitable for vegans, gluten free

$14.37/60 vegan capsules
10 45 325 133
(from yeast, form not stated)
GNC B-Complex (1 capsule, once daily)

Dist. by General Nutrition Corporation

Ingredients
50 50
(as niacina- mide)4
50 400
(as folic acid)
50 APPROVED 3 NA $0.09

Choline bitartrate, PABA

$8.99/100 capsules
50 50 50 50
(as cyanoco- balamin)
GNC B-Complex + Energy (1 capsule, once daily)8

Dist. by General Nutrition Corporation

Ingredients
50 25 50 200
(as folic acid)
NL APPROVED
Product also was tested for caffeine and was approved for that as well (listed amount is 100 mg per daily serving)
NA $0.12

Caffeine (100 mg per capsule), Choline

Contains no wheat, gluten free, yeast free

$14.999/120 capsules
50 50 100 100
(as cyanoco-balamin)
Life Extension Complete B-Complex (2 vegetarian capsules, once daily)

Dist. by Quality Supplements and Vitamins, Inc.

Ingredients
100 100
(as niacina- mide and niacin)4
100
(as pyridoxine HCl and pyridoxal 5'- phosphate) 5
800
(as folate)
100 APPROVED 3 NA $0.25

Choline bitartrate, PABA

$7.50/60 vegetarian capsules
100 200 1,000 100
(as methylco- balamin)
MegaFood Vegan B12 (1 tablet, once daily)

Mfd. by MegaFood

Ingredients
NL NL 20 400
(as folate)
NL NOT APPROVED
Vitamin B-6 and Vitamin B-12

Found 180.0% of listed amount of folate (720 mcg per tablet)
$0.45

Organic beet root  

Kosher, suitable for vegans, non-GMO, gluten free

$13.57/30 tablets
NL NL NA 500
(from yeast, form not stated)
Nutrilite® Natural B Complex (1 tablet, three times daily) 

Dist. by Amway Corp.

Ingredients
3.6 20 3.6 400
(as folic acid)
10.8 NOT APPROVED
Thiamin, Riboflavin, Niacin, Panto- thenic Acid, Vitamin B-6, and Vitamin B-12

Found 210.0% of listed amount of folic acid (840 mcg per tablet)
$0.21

PABA

Kosher

$20.99/300 tablet
3.6 15 NL 6
(form not stated)
Nutrition Now® B Complex (1 gummy, once daily) 

Mfd. by Nutrition Now® Inc. 

Ingredients
NL 20
(as inositol niacinate)
2 400
(as folic acid)
7 NOT APPROVED
Niacin, Vitamin B-6, Folic Acid, and Vitamin B-12

Found 228.0% of listed amount of panto- thenic acid (22.8 mg per gummy) and 169.3% of listed amount of biotin (127 mg per gummy)
NA $0.11

Contains no wheat, gluten free

$7.99/70 gummies
NL 10 75 30
(as cyanoco- balamin)
Thorne Research Stress B-Complex (1 vegetarian capsule, once to three times daily)

Mfd. by Thorne Research, Inc.

Ingredients
50 to 150 80 to 240
(as niacina- mide)4
28.4 to 85.2 (as pyridoxine HCl and pryidoxal 5'- phosphate) 200 to 600
(as L-5- methyltetra hydrofolate)
NA APPROVED NA $0.21-$0.63

Choline citrate

$12.50/60 vegetarian capsules
28.6 to 85.8
(as riboflavin and riboflavin 5'- phosphate sodium
250 to 750 80 to 2406 100 to 300
(as methylco- balamin)
Niacin (Vitamin B-3): [Cost Per 400 mg of Niacin]
NOW® Niacina mide (1 capsule, once daily) 

Mfd. by NOW Foods

Ingredients
NL 500
(as niacina- mide)4
NL NL NL APPROVED NA $0.04

[$0.03]  Lowest cost for Niacin

Contains no wheat, gluten free, yeast free

$4.25/100 capsules  
NL NL NL NL
Physio Logics Flush Free Niacin (1 capsule, once daily)

Mfd. by PhysioLogics, LLC

Ingredients
NL 400
(as inositol hexa- nicotinate)4
NL NL 100 APPROVED 3 NA $0.17

[$0.17]

Contains no wheat, gluten free, yeast free

$15.35/90 capsules
NL NL NL NL
SLO NIACIN® (1 tablet, once daily) 

Mfd. by Upsher-Smith Laboratories, Inc

Ingredients
NL 500
(as nicotinic acid)4
NL NL NL APPROVED $0.10

[$0.08]

Controlled release

$9.99/100 tablets
NL NL NL NL
Solaray® Niacin (1 capsule, once to five times daily) 

Mfd. by Nutraceutical Corp.

Ingredients
NL 500 to 2,500
(form not stated)4
NL NL NL APPROVED NA $0.04-$0.21

[$0.03]
Lowest cost for Niacin

$4.19/100 capsules
NL NL NL NL
Vitamin B-6 (Pyridoxine HCl): [Cost Per 50 mg of Vitamin B-6]
Country Life Vitamin B 6 (1 tablet, once daily)

Mfd. by Country Life, LLC

Ingredients
NL NL 50 NL NL APPROVED $0.06

[$0.06]

Kosher, suitable for vegans, contains no wheat, gluten free, yeast free

$5.99/100 tablets
NL NL NL NL
Klaire Labs® Vitamin B6 (1 vegetarian capsule, once daily) 

Mfd. by ProThera®, Inc. 

Ingredients
NL NL 2506 NL NL APPROVED NA $0.11

[$0.02]
Lowest cost for Vitamin B-6

Contains no wheat, gluten free, yeast free

$16.92/150 vegetarian capsules
NL NL NL NL
Nature's Plus® Vitamin B-6 (1 tablet, once daily) 

Mfd. by Natural Organics Laboratories, Inc.

Ingredients
NL NL 1005 NL NL APPROVED $0.07

[$0.03]

Suitable for vegetarians, contains no wheat, yeast free, hypo-allergenic

$6.12/90 tablets  
NL NL NL NL
Vitamin B-12: [Cost Per 500 mcg of Vitamin B-12]
CVS/ pharmacy® B-12 (1 tablet, once daily)

Dist. by CVS Pharmacy, Inc.

Ingredients
NL NL NL NL NL APPROVED $0.05

[$0.02]

Contains no wheat, gluten free, yeast free

$18.29/400 tablets
NL NL NL 1,000
(as cyanoco- balamin)
Dr. Mercola® Vitamin B-12 Energy Booster - Natural Cherry Flavor (6 sprays [0.78 ml], once daily) 

Dist. Mercola Health Resources, LLC

Ingredients
NL NL NL NL NL APPROVED NA $0.61

[$0.31]

$19.52/0.85 fl. oz. [25 ml] container (approx. 32 servings)
NL NL NL 1,000
(as methylco- balamin)
Jamieson Natural™ B12 (1 tablet, once daily)

Dist. by Jamieson Laboratories

Ingredients
NL NL NL NL NL APPROVED NA $0.17

[$0.07]

Timed release

Suitable for vegetarians, gluten free

$30.95/180 tablets
NL NL NL 1,200
(as cyanoco- balamin)
Natural Factors B12 (1 chewable tablet, once daily)

Dist. by Natural Factors Canada

Ingredients
NL NL NL NL NL APPROVED NA $0.12

[$0.05]

Contains no wheat, gluten free, yeast free

$10.47/90 chewable tablets
NL NL NL 1,200
(as methylco- balamin)
Nature Made® B-12 (1 tablet, once daily)

Dist. by Nature Made Nutritional Products

Ingredients
NL NL NL NL NL APPROVED $0.06

[$0.06]

Gluten free, yeast free

$6.29/100 tablets
NL NL NL 500
(as cyanoco- balamin)
Nature's Bounty® Quick Dissolve B-12 - Natural Cherry Flavor (1 dissolvable tablet, once daily) 

Mfd. by Nature's Bounty, Inc.

;Ingredients
NL NL NL NL NL APPROVED NA $0.17

[$0.03]

Gluten free, yeast free

$8.28/50 dissolvable tablets
NL NL NL 2,500
(as cyanoco- balamin)
NOW® B-12 (1 lozenge, once daily)

Mfd. by NOW Foods

Ingredients
NL NL NL NL NL APPROVED NA $0.08

[$0.02]

Suitable for vegans/ vegetarians, gluten free, yeast free

$7.63/100 lozenges
NL NL NL 2,000
(as cyanoco- balamin, methylco- balamin and dibemco- zide)
Rexall® B-12 (1 tablet, once daily)

Mfd. by Rexall Sundown, Inc.

Ingredients
NL NL NL NL NL APPROVED NA $0.09

[$0.02]

Contains no wheat, gluten free, yeast free

$5.65/60 tablets  
NL NL NL 2,500
(as cyanoco- balamin)
Solgar® Vitamin B 12 (1 nugget, once daily)

Mfd. by Solgar, Inc.

Ingredients
NL NL NL NL NL APPROVED NA $0.09

[$0.05]

Kosher, contains no wheat, gluten free, yeast free

$9.04/100 nuggets
NL NL NL 1,000
(as cyanoco- balamin)
Spring Valley® [Wal-Mart] B 12 - Natural Cherry Flavor (1 microlozenge, once daily)

Dist. by Wal-Mart Stores, Inc.

Ingredients
NL NL NL NL NL APPROVED NA $0.07

[$0.01]
Lowest cost for Vitamin B-12

Contains no wheat, gluten free, yeast free

$8.44/120 microlozenges
NL NL NL 2,500
(as cyanoco- balamin)
Twinlab® B-12 Dots™ (1 tablet, once daily)

Mfd. by ISI Brands Inc.

Ingredients
NL NL NL NL NL APPROVED $0.04

[$0.04]

Suitable for vegetarians

$3.75/100 tablets  
NL NL NL 500
(as cyanoco- balamin)
The Vitamin Shoppe® Vitamin B12 (1 capsule, once daily) 

Dist. by Vitamin Shoppe, Inc

Ingredients
NL NL NL NL NL APPROVED NA $0.05

[$0.05]

Contains no wheat, gluten free

$5.49/100 capsules
NL NL NL 500
(as cyanoco- balamin)
Similar to Approved Products*:
Puritan's Pride® B-12 (1 microlozenges, once daily) 

Mfd. by Puritan's Pride, Inc.

Ingredients
Similar to Spring Valley® B 12.
Vitamin World® B-12 (1 microlozenges, once daily) 

Mfd. by Vitamin World, Inc.

Ingredients
Similar to Spring Valley® B 12.
Biotin (Vitamin B-7): [Cost Per 1,000 mcg of Biotin]
Bluebonnet Biotin (1 Vcap, once daily)

Mfd. by Bluebonnet Nutrition Corporation

Ingredients
NL NL NL NL NL APPROVED NA $0.11

[$0.11]

Kosher, suitable for vegans, contains no wheat, gluten free, yeast free

$9.56/90 Vcaps
NL NL 1,000 NL
Nature's Life® Biotin 2,500 mcg Hair, Skin & Nails Formula (1 vegetarian capsule, once daily) 

Mfd. by Nature's Life

Ingredients
NL NL NL NL NL APPROVED NA $0.09

[$0.04]

Suitable for vegetarians

$9.40/100 vegetarian capsules
NL NL 2,500 NL
Vitacost® Quickdot™ Chewables (2 vegetarian chewable tablets, once daily) 

Dist. by Vitacost

Ingredients
NL NL NL NL NL APPROVED NA $0.10

[$0.03]
Lowest cost for Biotin

$2.99/60 vegetarian tablets
NL NL 3,000 NL
Folate (Folic Acid, Vitamin B-9): [Cost Per 400 mcg of Folate]
Douglas Labora- tories® Folic Acid (1 tablet, once daily) 

Mfd. by Douglas Laboratories

Ingredients
NL NL NL 400
(as folic acid)
NL APPROVED $0.10

[$0.10]

Contains no wheat, gluten free, yeast free

$8.80/90 tablets
NL NL NL NL
Finest Nutrition [Walgreens] Folic Acid (1 tablet, once daily)

Dist. by Walgreen Co.

Ingredients
NL NL NL 400
(as folic acid)
NL APPROVED $0.02

[$0.02]

Contains no wheat, gluten free, yeast free

$6.49/400 tablets
NL NL NL NL
Jarrow Formulas® Methyl Folate (1 capsule, once daily) 

Dist. by Jarrow Formulas® 

Ingredients
NL NL NL 400
(as Quatre- folic® (6S)-5- methyltetra- hyrofolic acid glucosa- mine salt)
NL APPROVED NA $0.15

[$0.15]

Contains no wheat, gluten free

$8.99/60 capsule  
NL NL NL NL
Rite Aid® Folic Acid 400 (1 tablet, once daily)

Dist. by Rite Aid

Ingredients
NL NL NL 400
(as folic acid)
NL APPROVED $0.02

[$0.02]

$5.49/250 tablets
NL NL NL NL
Thorne Research 5-MTFH (1 vegetarian capsule, once to three times daily)

Mfd. by Thorne Research, Inc.

Ingredients
NL NL NL 1,000 to 3,000
(as L-5- methyltetra- hydro- folate)7
NL APPROVED NA $0.31-$0.93

[$0.12]

Hypo-allergenic

$18.65/60 vegetarian capsules
NL NL NL NL
Whole Foods Folic Acid (1 tablet, once daily)

Dist. by Whole Foods Market

Ingredients
NL NL NL 800
(as folic acid)
NL APPROVED $0.03

[$0.02]
Lowest cost for Folate

Suitable for vegetarians

$3.49/100 tablets
NL NL NL NL
Pantothenic Acid (Vitamin B-5): [Cost Per 500 mg of Pantothenic Acid]
Nature's Way® Panto- thenic Acid (2 capsules, once daily) 

Dist. by Nature's Way Products, Inc.

Ingredients
NL NL NL NL NL APPROVED NA $0.15

[$0.15]

Calcium

$7.29/100 capsules
NL 500 NL NL
Tested through CL's Quality Certification Program prior to, or after initial posting of this Product Review.

  - Canadian Product

* Product identical in formulation and manufacture to a product that has passed testing but sold under a different brand. For more information see CL's Multi-Label Testing Program.

1 Products were only tested for lead, cadmium and arsenic if they contain 250 mg or more of whole herbs and/or minerals per daily dosage.
2 Not tested but claimed on label.
3 Product was not tested for inositol.
4 Maximum suggested daily serving size exceed Upper Tolerable Intake Level (UL) for niacin (35 mg for adults). For niacin in the niacinamide form, note that agencies in Europe have established much higher limits than in the U.S., as this form does not cause skin flushing. For details, see Niacin below.
5 Suggested daily serving size is at the Upper Tolerable Intake Level (UL) for Vitamin B-6 (100 mg for adults).
6 Maximum suggested daily serving size exceed Upper Tolerable Intake Level (UL) for Vitamin B-6 (100 mg for adults).
7 Maximum suggested daily serving size exceed Upper Tolerable Intake Level (UL) for Folate (1,000 mcg for adults).
8 Product was added on 2/27/2015.
9 Product was purchased as the "Deal of the Day". Regular price is $22.99.
Unless otherwise noted, information about the products listed above is based on the samples purchased by ConsumerLab.com (CL) for this Product Review. Manufacturers may change ingredients and label information at any time, so be sure to check labels carefully when evaluating the products you use or buy. If a product's ingredients differ from what is listed above, it may not necessarily be of the same quality as what was tested.

The information contained in this report is based on the compilation and review of information from product labeling and analytic testing. CL applies what it believes to be the most appropriate testing methods and standards. The information in this report does not reflect the opinion or recommendation of CL, its officers or employees. CL cannot assure the accuracy of information.  
Copyright ConsumerLab.com, LLC, 2014. All rights reserved. Not to be reproduced, excerpted, or cited in any fashion without the express written permission of ConsumerLab.com LLC.
    
RESULTS OF CONSUMERLAB.COM TESTING OF ENERGY DRINKS & SHOTS
Click on beneath a product name to find a vendor that sells it.
To find retailers that sell some of the listed products click here.
Product Name, Serving Size, and Suggested Daily Dose on Label

Click on "Ingredients" for Full Listing
Claimed Amount of B Vitamins Per Suggested Daily Serving
[Recommended Daily Intake for Adults]
(NL= Not Listed) (mg=milligram; mcg=microgram)
--TEST RESULTS--
(See How Products Were Evaluated)
Cost for Daily Suggested Serving on Label

Other Notable Ingredients/ Features1

Price Paid
B-1
(Thiamin) (mg)
[1.1 — 1.2 mg]
B-3
(Niacin) (mg)
[14 — 15 mg]
B-6
(Pyridoxine) (mg)
[1.3 — 1.7 mg]
B-9
Folate (mcg)
[400 mcg]
Caffeine (mg) OVERALL RESULTS: APPROVED
or
NOT APPROVED
Contained Labeled Amount of B Vitamins Contained Labeled Amount of Caffeine
B-2
(Ribo- flavin) (mg)
[1.1 — 1.3 mg]
B-5
(Panto- thenic Acid) (mg)
[5 — 6 mg]
B-7
Biotin (mcg)
[30 mcg]
B-12
(mcg)
[2.4 mcg]
Energy Drink Products:
5-hour Energy® - Berry (1 bottle, 0.5 to 2 daily) 

Dist. by Living Essentials

Ingredients  
NL 15-60
(as niacina- mide)4
20-80 200-800
(as folic acid)
90-3602 NOT APPROVED
Vitamin B-6, Niacin and Folic Acid

Found only 72.3% of listed amount of vitamin B-12 (361.4 mcg per serving)

(Found 221.2 mg per bottle)
$0.89-$3.54

Sodium, taurine, glucuronic acid, malic acid, n-acetyl l-tyrosine, l-phenylalanine, citicoline

Kosher

$21.24/12 bottles [1.93 fl. oz] (approx. 12 servings)
NL NL NL 250-1,000
(as cyanoco- balamin)
MioEnergy Liquid Water Enhancer - Black Cherry (1/2 tsp. [2.5 ml], no recommended daily serving size)

Dist. by Kraft Foods Group, Inc.

Ingredients
NL 2
(as niacina- mide)3
0.23 NL 603 NOT
APPROVED

Vitamin B-12

Found 200.0% of listed amount of niacin (4 mg per serving) and 227.5% of listed amount of vitamin B-6 (0.46 mg per serving)
$0.193

$3.48/1 bottle [22 fl. oz.] (approx. 18 servings)  
NL NL NL 0.6
(form not stated)3
NOS® High Performance Energy Drink (12 fl. oz. [54.5% of bottle].) 

Dist. by Energy Brands Inc.

Ingredients
NL NL 33 NL 1223 APPROVED
Vitamin B-6
$1.503

$2.99/1 bottle [22 fl. oz.] (approx. 2 servings)  
NL NL NL 9*
(as cyanoco- balamin)3
Rockstar® Zero Carb (8 fl. oz. [1/2 bottle]) 

Dist. by Rockstar, Inc.

Ingredients  
NL 20
(as niacina- mide)3
23 NL 1203 NOT
APPROVED

Niacin

Found 213.6% of listed amount of vitamin B-6 (4.3 mg per serving), 274.4% of listed amount of vitamin B-12 (16.5 mcg per serving), and 70.8% of listed amount of pantothenic acid (7.1 mg per serving)
$1.003

L-carnitine

$1.99/1 can [16 fl. oz.] (approx. 2 servings)  
NL 103 NL 6
(as cyanoco- balamin)3
* - Unable to determine vitamin B-12 value in testing.

1 Not tested but claimed on label.
2 5 hour Energy claims amount in one bottle is comparable to "cup of the leading premium coffee," which CL assumes to be approximately 180 mg based on data from Starbucks. A cup of regular brewed coffee contains, on average, 95 mg of caffeine.
3 Based on 1 serving daily.
4 Maximum suggested daily serving size exceed Upper Tolerable Intake Level (UL) for niacin (35 mg for adults). For niacin in the niacinamide form, note that agencies in Europe have established much higher limits than in the U.S., as this form does not cause skin flushing. For details, see Niacin below.
Unless otherwise noted, information about the products listed above is based on the samples purchased by ConsumerLab.com (CL) for this Product Review. Manufacturers may change ingredients and label information at any time, so be sure to check labels carefully when evaluating the products you use or buy. If a product's ingredients differ from what is listed above, it may not necessarily be of the same quality as what was tested.

The information contained in this report is based on the compilation and review of information from product labeling and analytic testing. CL applies what it believes to be the most appropriate testing methods and standards. The information in this report does not reflect the opinion or recommendation of CL, its officers or employees. CL cannot assure the accuracy of information.  
Copyright ConsumerLab.com, LLC, 2014. All rights reserved. Not to be reproduced, excerpted, or cited in any fashion without the express written permission of ConsumerLab.com LLC.

ConsumerTips™: on Buying and Using:

Be sure that you are getting enough B vitamins to meet basic nutrient requirements and avoid deficiencies. Check the recommended intakes listed below for each. These values, known as Dietary Reference Intakes (DRIs), are established by the Institute of Medicine of the National Academies. One type of DRI is a Recommended Dietary Allowance (RDA) -- the average daily dietary intake level that is sufficient to meet the nutrient requirement of nearly all healthy individuals in a particular life stage and gender. Another type of DRI is an Adequate Intake (AI), which is similar to an RDA but is more of an approximation used when there is not sufficient information to develop an RDA.

Don't base your requirements on DV values on labels: As required by the FDA, dietary supplement labels or packages must show the percent of the Daily Value for certain vitamins and minerals that they contain. However, the DVs, which were set in 1968, were not updated to reflect the latest Recommended Dietary Allowances (RDAs) or Adequate Intakes (AIs) until July 2016 and it may take until 2019 for all labels to be corrected. The old DVs tend to be higher than the RDIs for most B vitamins, as shown in the table below. For a quick reference chart of current RDAs and AIs for B vitamins and other nutrients go to www.ConsumerLab.com/RDAs. That table includes specific values by life stage and gender. You will also find that information in the B-vitamin specific information further below in this report. 

Comparison of Established DV (Daily Value) and DRI (Dietary Reference Intake) Values for B Vitamins
  Riboflavin (B-2) Niacin (B-3) Vitamin B-6 Folate (B-9) Vitamin B-12 Biotin (B-7) Pantothenic Acid (B-5)
Old (Pre-2016) DV (adult) 1.7 mg 20 mg 2 mg 400 mcg 6 mcg 300 mcg 10 mg
New DV (4 & older)
(on labels starting 2018)
1.3 mg 16 mg 1.7 mg 400 mcg DFE* 2.4 mcg 30 mcg 5 mg
RDA or AI (adult) 1.1 to 1.3 mg 14 to 15 mg 1.3 to 1.7 mg 400 mcg DFE* 2.4 mcg 30 mcg** 5 to 6 mg**
* DFE = Dietary Folate Equivalents; 1 DFE = 1mcg naturally-occurring folate = 0.6 mcg folic acid.
** AI value (RDA not established)
Sources: DVs: FDA Food Labeling Guide
RDA/IA: ConsumerLab.com Summary of RDAs and AIs. Values shown above exclude special values for lactating and pregnant women, which are available in the full listing.

If you are buying B vitamins to treat a specific medical condition, such as treating high cholesterol with niacin or correcting B vitamin deficiency, you will generally need more than the recommended intakes. Look at each vitamin for suggested doses for treating specific conditions.

In either case, be aware that you can get "too much" of some vitamins. A Tolerable Upper Intake Level (UL) is the highest level of daily intake of a nutrient that is likely to pose no risk of adverse health effects for most people. As intakes increase above the UL, the risk of adverse effects may increase. Like the RDAs and AIs, the ULs vary according to age, and gender. Individuals are advised not to regularly exceed the UL, unless medically recommended and supervised. Be aware that products are not required to provide information indicating whether their ingredients may exceed ULs for the individuals for whom they are intended. As discovered by ConsumerLab.com, many do exceed these ULs. Most products list the amount of each ingredient in the Supplement Facts panel on the side label, so check it along with the Suggested Use to determine how much of each ingredient you'll be getting daily. The information provided below can help you determine whether such amounts are appropriate. Keep in mind that 1,000 mcg (micrograms) is the same as 1 mg (milligram), and 1,000 mg equals 1 gram.

MTHFR gene mutation and B vitamin metabolism
MTHFR gene mutation is a genetic change that affects an enzyme involved in breaking down the amino acid, homocysteine and converting folate and folic acid into its active form, L-methylfolate. Roughly 33% of Americans carry one copy of a common MTHFR gene mutation (C677T). People who carry two C677T mutations, which is about 11% of Americans, have a 16% higher chance of developing coronary heart disease compared to people without these mutations and have elevated levels of homocysteine in their blood (homocysteinemia) or urine (homocystinuria) (NIH Genetic and Rare Disease Information Center). MTHFR gene mutations are also associated with an increased risk of other conditions, but a cause-and-effect relationship has not been established (Liew, Eur J Med Genet 2015; Gilbody, Am J Epidemiol 2007).

Currently there are no treatments to remove adverse risks associated with MTHFR gene mutations. However, elevated levels of homocysteine can also occur if there is a lack of folate or B vitamins. Homocysteine levels also tend to rise with age, smoking, and use of certain drugs (such as carbamazepine, methotrexate, and phenytoin).

It is important to ensure that people with and without MTHFR gene mutations receive adequate amounts of naturally occurring folate, choline, and B vitamins (B12, B6, and riboflavin) to mitigate nutritional risks. If adequate nutrition cannot be attained through diet alone, supplementation with folate (e.g., levomefolate (5-methyl THF) or folinic acid) and B vitamins is considered.

People with C677T mutations may be more likely to have a deficiency in vitamin B-12 (Zittan, Am J Physiol Heart Circ Physiol 2007). Taking vitamin B2 (riboflavin) may also be helpful for people with C677T mutation who also have high blood pressure However, according to the American College of Medical Genetics and Genomics there is currently "no evidence that specific treatments reduce risks associated with hyperhomocysteinemia or MTHFR genotype status." (Hickey, Genet Med 2013). (See the sections on Folate, Vitamin B-12 and Riboflavin below for more information).

B Complexes:
Supplements containing more than one B vitamin are widely sold. However, two common reasons for buying these complexes are not well supported by scientific evidence:

- Reduction of cardiovascular risk -- Some of the interest in B complexes comes from studies showing the combination of B-6, B-12, and folate can reduce elevated levels of homocysteine -- a risk factor for cardiovascular disease. Unfortunately, trials have failed to show that this combination reduces cardiovascular risk itself, leading the American Heart Association to conclude that the available evidence "is inadequate to recommend folate and other B vitamin supplements as a means to reduce cardiovascular disease risk." (AHA Recommendations — Circulation 2006)

- Increased energy -- B vitamins, such B-12 and folate, are involved in the metabolism of food to create energy. However, if you are not deficient in B vitamins and already get an adequate amount of the B vitamins in your diet, supplementing with additional amounts of B vitamins is not known to improve performance (Lukaski, Nutrition 2004). Nevertheless, many supplements such as the "shot-sized" drinks tested in this Review remain touted as energy boosters; the real boost would appear to come from the often unspecified amounts of caffeine added to many of these products.

The B Vitamins:

  • Thiamin hydrochloride (Thiamine) (B-1) assists the nervous system. It is found in large enough amounts in yeast, peas, beans, and grains that if these foods are regularly included in the diet, supplementation is normally not necessary. Thiamin deficiency, however, can occur in people taking strong diuretics (loop diuretics) for congestive heart failure, and this deficiency itself can adversely affect heart function. Thiamin deficiency is also common in people who abuse alcohol. Thiamin is also found in supplements as thiamin mononitrate.
    Recommended Intake: The RDA is 0.5 mg for children 1 to 3, 0.6 mg for those 4 to 8, and 0.9 mg for those 9 to 13. For males 14 years and older the RDA is 1.2 mg. For females 14 to 18 the RDA is 1.0 mg, and it increases to 1.1 mg for those 19 and older. However, the RDA for pregnant or lactating women is 1.4 mg. For use to counter the effects of diuretics, a dose of 100 mg twice daily has been used.
    Upper Limit: No UL has been established for thiamin. This appears to be a non-toxic supplement.

    See the Encyclopedia article on Thiamin for more information about clinical use.

    Benfotiamine is a derivative of thiamin (B-1) that has been shown to significantly increase blood and tissue levels of thiamin compared to thiamin hydrochloride and thiamin mononitrate (Bitsch, Ann Nutr Metab 1991; Xie, J Clin Pharamacol 2014). It is commonly promoted to prevent or slow the progression of complications due to diabetes, such as diabetic nerve pain and vascular disease, although this is supported mainly by preliminary animal and in-vitro studies and some small studies in people (Pacal, World J Diabetes 2014). One small, randomized, placebo-controlled double-blind clinical study found that a daily dose of 200 mg benfotiamine (two 50 mg tablets four times daily) for 3 weeks significantly improved neuropathy scores and reduced pain in type 1 and type 2 diabetes patients with polyneuropathy (Haupt, Int J Clin Pharmacol Ther 2005). In people with kidney disease associated with type 2 diabetes, taking 900 mg/ day of benfotiamine for 3 months significantly improved thiamin status but did not improve measures of kidney functioning (Alkhalaf, Diabetes Care 2010). There is no recommended intake or UL established for benfotiamine, but oral daily doses used in clinical studies tend to range from 200 — 800 mg. There are no reports of toxicity.   

  • Riboflavin (B-2) maintains vision and skin. Although found in beef (2.9 mg per 3 oz serving), enriched wheat flour (about 0.5 mg per cup), fortified breakfast cereals (0.4 to 2.5 mg per cup), dairy foods (0.4 mg per cup of milk or yogurt) and certain vegetables (see full USDA list), some supplementation may be needed in children and the elderly. Individuals with a certain genetic type (known as MTHFR 677TT, which affects about 10% of people worldwide and a greater percentage in Northern China (20%) and in Mexico (32%), are predisposed to high blood pressure which may be reduced with low-dose riboflavin supplementation (Wilson, Am J Clin Nutr 2012). A small, placebo-controlled study in people with this genetic type showed that 1.6 mg of riboflavin daily for 16 weeks reduced systolic and diastolic blood pressures by approximately 9.2 mm Hg and 6.0 mm Hg, respectively. Interestingly, these individuals were also taking prescription antihypertensive medication but many had not achieved acceptable blood pressure levels until the riboflavin supplement was also taken. [Note: It is difficult to find a low-dose riboflavin supplement on the market (most provide a high dose of 100 mg) and none are included in this Review. Food sources remain a good option for most people.]
    Recommended Intake: The RDA is 0.5 mg for children 1 to 3, 0.6 mg for those 4 to 8, and 0.9 mg for those 9 to 13. For males 14 years and older the RDA is 1.3 mg. For females 14 to 18 the RDA is 1.0 mg, and it increases to 1.1 mg for those 19 and older. However, the RDA for pregnant women is 1.4 mg and for lactating women it is 1.6 mg. Much higher amounts (400 mg per day) have been suggested in the prevention of migraines (Schoenen, Cephalalgia 1994).
    Upper Limit: No UL has been established for riboflavin.

    See the Encyclopedia article on Riboflavin for more information about clinical use.

  • Niacin (Nicotinic Acid) (B-3) helps release energy from carbohydrates, enhance DNA repair, and prevents pellagra — a disease caused by long-term niacin or tryptophan deficiency, characterized by delusions, diarrhea, and scaly skin sores. Niacin is available in the diet from enriched white flour as well as peanuts, fish and meat.

    When taken in very high doses, it can help improve cholesterol levels -- lowering LDL ("bad") cholesterol, raising HDL ("good") cholesterol, and lowering elevated triglycerides. However, studies show that if you already take a statin drug, adding high-dose niacin does not appear to provide additional benefit and may carry serious risks. For example, one study found that adding high dose niacin to statin drug treatment in people with heart and vascular disease did not reduce the risk of cardiovascular events (including heart attacks and stroke) despite improving HDL and triglyceride levels (NIH News, May 26, 2011 and Boden, NEJM 2011). Patients in the study were given 1,500 to 2,000 mg per day of extended-release nicotinic acid as Niaspan, a prescription drug. The study was stopped early when there was no improvement in outcomes after 32 months of treatment and a small increase in ischemic stroke was noted among those taking Niaspan compared to those taking placebo. Similarly, in a 4-year study using 2,000 mg of extended-release niacin given daily along with an anti-flushing drug (laropiprant) to patients already taking statins, the addition of niacin provided no worthwhile benefit and was associated with a significant increases in disturbances in diabetes control (3.7 percentage points higher than in those not receiving niacin) as well as smaller, but significant, increases in infections, new onset diabetes, problems of the gastrointestinal and musculoskeletal systems, bleeding, and skin problems (Landray, NEJM 2014). Based on this evidence, high-dose niacin would also not be recommended for use with red yeast rice, which naturally contains statin compounds. However, for patients who cannot tolerate statin drugs, high dose niacin currently remains a viable stand-alone treatment without increasing the risk of ischemic strokes (Maningat, NEJM 2011) and some physicians believe that niacin in conjunction with statins may be helpful to certain patients -- so consult your physician.

    A modified form of niacin called inositol hexanicotinate (or hexaniacinate) is said to cause less flushing than regular niacin. It may also reduce cholesterol levels. It has been studied particularly as a treatment for intermittent claudication (a kind of leg cramping caused by hardening of the arteries), as well as for Raynaud's disease (another condition that involves arterial blood flow.) One small study found a daily dose of 4 grams of inositol hexanicotinate significantly reduced the number of attacks in people with Raynaud's disease compared to placebo (Sunderland, Clin Rheumatol 1988). Niacinamide (or nicotinamide) is another form of niacin which does not cause flushing; it does not lower cholesterol. High doses of niacinamide were found to protect mice from memory loss associated with Alzheimer's disease (Green, J Neurosci 2008). Healthy mice fed the vitamin outperformed mice on a normal diet. The mice were fed an amount equivalent in humans to 2 to 3 grams per day. Another form of niacin, nicotinamide riboside (sold as Niagen) has also been promoted to not cause flushing (although this may be false, as noted below), and may lower cholesterol levels in the liver as well as improve glucose control, according to laboratory and animal studies (Lee, J Med Food 2015). Studies in mice have also shown it to reduce a main component of amyloid plaque associated with Alzheimer's disease and improve cognitive function (Gong, Neurobiol Aging 2013) and to improve stem cell function (Zhang, Science 2016). Researchers theorize this effect in mice may be due to the fact that nicotinamide riboside is a precursor of nicotinamide adenine dinucleotide (also called NADH or NAD+) — a substance which needed in the production of energy in the mitochondria of cells. A study by the maker of Niagen, ChromaDex, among 11 healthy men and women showed that a one-time dose of Niagen of 100 mg, 300 mg or 1,000 mg (providing about 42 mg, 126 mg, and 420 mg of niacin) increased NAD+ levels without any serious adverse events, although two people reported flushing at the 300 mg dose and two others reported "feeling hot" at the 1,000 mg dose (Trammell, Nat Commun 2016). (Supplements typically provide about 250 mg nicotinamide riboside per daily dose.) There are no long term studies investigating the safety or efficacy of nicotinamide riboside in people.

    High dose niacin (500 mg from nicotinamide twice daily) for 12 months appeared to reduce the risk of developing non-melanoma skin cancer (i.e., squamous and basal cell cancer) by 23% in older adults who had a history of these lesions in a placebo-controlled study in Australia (Martin, J Clin Oncol 2005 suppl; abstr 9000). Benefits were evident within 3 months, but no continuing benefit was found 6 months after treatment stopped — i.e., it only helped while being taken (Chen, NEJM 2015). The benefit may be due to enhanced DNA repair and reducing the immunosuppressive effect of UV radiation. Be aware, however, that niacin fortification of food is not mandated in Australia, which is also the country with the highest incidence of skin cancer in the world. Consequently, it is difficult to say if the same level of benefit would be expected in countries such as the U.S. and Canada — both of which require food fortification with niacin (although only at amounts needed to meet RDAs).

    Recommended Intake: The RDA is 6 mg for children 1 to 3, 8 mg for those 4 to 8, and 12 mg for those 9 to 13. For males 14 years and older the RDA is 16 mg. For females 14 and older the RDA is 14 mg. However, the RDA for pregnant women is 18 mg and for lactating women it is 17 mg. Niacin has documented effects for improving cholesterol profile, but only when taken in doses that are far higher than the RDAs and ULs, ranging from 1,000 mg to 4,000 mg (1 to 4 grams) per day. Liver injury is a real possibility when niacin is used in this way. Be aware that the amount of niacin in inositol hexanicotinate is about 85% of the total compound, i.e., if the front of the bottle says 600 mg inositol hexanicotinate, the product should be expected to have about 500 mg of niacin.
    Upper Limit: Daily doses over 50 mg per day have been associated with flushing of the skin, including reddening, burning, tingling, itching and pain. Starting with a lower dose and then gradually increasing it may reduce this side effect, as may taking the supplement with food. Slow-release niacin and products made from nicotinamide (or niacinamide) and inositol hexanicotinate are also less likely to cause this reaction. However, at doses over 1,500 mg (1.5 grams) of niacin or 3,000 mg (3 grams) of nicotinamide per day liver toxicity can occur and may be more common among people taking slow-release niacin (though it is also possible that the flushing side effect simply makes many people unable to use high dosages of ordinary niacin). Elevated liver enzymes may occur without symptoms in up to 20% of people when taking a daily dose of niacin above 500 mg, and two cases of acute hepatitis have been reported in otherwise healthy adults who consumed between 160 mg and 300 mg of niacin daily from energy drinks (Harb, BMJ Case Rep 2016). The UL for niacin applies only to that consumed from supplements and fortified foods (other naturally occurring food sources are not included) and is 10 mg for children 1 to 3, 15 mg for those 4 to 8, 20 mg for those 9 to 13, 30 mg for those 14 to 18, and 35 mg for individuals 19 years and older. Cautions: High-dose niacin may impair glucose control, elevating blood glucose levels; Niacinamide may increase blood levels of anticonvulsant drugs. As niacinamide does not cause skin flushing but may still cause toxicity at very high doses, government agencies in Europe have set higher ULs for niacinamide than established in the U.S. -- 500 mg in the UK and 900 mg in the European Union for adults.

    See the Encyclopedia article on Niacin for more information about clinical use.

  • B-5 (Pantothenic Acid) is involved in the production of energy as well as the synthesis of hormones and neurotransmitters. Deficiency is rare (although seen in alcoholics) and it is found in many foods, with particularly high levels in liver, yeast, and salmon.
    Recommended Intake: The AI is 2 mg for children 1 to 3, 3 mg for children 4 to 8, and 4 mg for children 9 to 13. For individuals 14 years and older the AI is 5 mg. However, the AI for pregnant women is 6 mg, and for women who breastfeed it is 7 mg. Much higher doses (900 mg per day) of the related substance pantothenate have been used in improving cholesterol profile (especially reducing triglyceride levels)
    Upper Limit: No UL has been established for pantothenic acid.

    See the Encyclopedia article on Pantothenic Acid for more information about clinical use.

  • B-6 (Pyridoxine hydrochloride, Pyridoxal-5-phosphate, P-5-P) is important in many aspects of metabolism and in maintaining the immune and nervous systems. Pyridoxine hydrochloride is converted in the body to pyridoxal-5-phosphate, the active form of B-6. Most supplements in the U.S. contain the pyridoxine hydrochloride form, although some contain pyridoxal-5-phosphate, or a combination of both forms. Although supplements providing pyridoxal-5-phosphate (also called P-5-P or PLP) provide the "active form" of vitamin B6, this form must still undergo conversion in the intestine in order to be absorbed, so bioavailability may be no better than that of pyridoxine for most people (European Food Safety Authority 2008). People with certain conditions that prevent the body from converting pyridoxine into pyridoxal-5-phosphate (such as pyridoxal 5'-phosphate-dependent epilepsy), however, may be prescribed the pyridoxal-5-phosphate form of B6. Very preliminary research has found pyridoxal-5-phosphate may be more effective than other forms of vitamin B6 in slowing kidney damage, neuropathy, and lipid oxidation in animal models of diabetes, however there do not appear to be any studies of these uses in people (Nakamura, J Am Soc Nephrol 2005; Higuchi, J Lipid Res 2006). Pyridoxine in amounts that meet the RDAs is easily available from the diet, however mild deficiency is common (10.5% of the U.S. population is deficient according to the CDC), particularly in the elderly and children. A recent study found that people with higher blood levels of vitamin B-6 and methionine (an amino acid) were 50% less likely to develop lung cancer than people with low blood levels of these two nutrients. However, no association was found with the intake of vitamin B-6 -- that is, taking more B-6 was not shown to reduce the risk of lung cancer (Johansson, JAMA 2010).
    Recommended Intake: The RDA is 0.5 mg for children 1 to 3, 0.6 mg for those 4 to 8, and 1.0 mg for those 9 to 13. For males 14 to 50 the RDA is 1.3 mg, and for those 51 and older it is 1.7 mg. For females 14 to 18 it is 1.2 mg, for those 19 to 50 it is 1.3 mg, and for those 51 and older it is 1.5 mg. However, the RDA for pregnant women it is 1.9 mg and for lactating women it is 2.0 mg. Amounts higher than the RDA but lower than the ULs have been recommended to help reduce the risk of heart disease (5 - 30 mg/day) and reduce the nausea of morning sickness (30 mg/day); some evidence supports these uses. Other proposed uses of pyridoxine such as treating asthma, autism, carpal tunnel syndrome, diabetic neuropathy, tardive dyskinesia and PMS may involve doses higher than the ULs; however, none of these uses has good scientific support.
    Upper Limit: Too much pyridoxine can cause nerve damage and skin lesions. These effects are generally seen at doses over 1,000 mg per day, though rare cases have been seen at 200 mg daily. Some cases of gastrointestinal disturbances such as heartburn, nausea and indigestion, and photosensitivity have been reported at doses between 100 and 200 mg per day (Bendich, Ann N Y Acad Sci 1990). The UL for pyridoxine is 30 mg for children 1 to 3, 40 mg for those 4 to 8, 60 mg for those 9 to 13, 80 mg for those 14 to 18, and 100 mg for individuals 19 years and older. Keep in mind that all sources of pyridoxine count toward these upper limits, including that from food sources and multivitamins.

    Some evidence suggests pyridoxal-5-phosphate may not cause the nerve damage or skin lesions associated with excessive doses of pyridoxine, although high doses of pyridoxal-5-phosphate have been reported to cause an increase in seizure frequency and liver damage in infants (Clayton, J Inherit Metab Dis 2006). The same upper tolerable limits  noted above for pyridoxine apply to P-5-P, In fact, the European Food Safety Authority came to this same conclusion — suggesting an even lower UL for all forms of vitamin B6 of 25 mg per day for adults and 5 to 20 mg per day for children depending on their body weight (European Food Safety Authority 2008).

    One clinical study found that a daily dose of 25 mg B-6 taken as part of a B-vitamin complex doubled the risk of heart attack, stroke and death in diabetes patients with advanced kidney disease (See Cautions and Concerns section below.)

    Also be aware that preliminary evidence suggests B-6 could potentially increase the effects of antihypertensive drugs such as diltiazem (Cardizem), amlodipine (Norvasc), and may interfere with some drugs for Parkinson disease. A dose of 200 mg daily B-6 may reduce the effectiveness of the anti-seizure drug phenytoin (Dilantin) (Hansson, Lancet 1976).

    See the Encyclopedia article on Vitamin B-6 for more information about clinical use.

  • Biotin (B-7) is needed for the metabolism of nutrients. Deficiency is rare under normal circumstances, because biotin can be produced in the gut by bacteria and is also found in organ meats, oatmeal, egg yolk, mushrooms, bananas, peanuts and brewer's yeast. Deficiency might occur with long-term use of antibiotics or anti-seizure medications; NOTE: there are concerns that use of biotin might impair absorption of some anti-seizure medications, and for this reason people taking such medications should only use biotin supplements under the supervision of a healthcare professional. A small, but controlled, study among women with brittle nails found that a daily dose of 2,500 mcg of biotin for 6 to 9 months increased nail thickness by 25% and reduced their tendency to split (Columbo, J Am Acad Dermatol 1990). Biotin does not, however, further strengthen healthy nails. Very high doses of biotin (e.g. hundreds of milligrams — over 10,000 times the daily requirement) can cause misleading laboratory results by fully mimicking the typical laboratory pattern of Graves' disease and sometimes persisting for several days after biotin application. This may lead to unnecessary antithyroid treatment and thereby cause unrecognized hypothyroidism that might be deleterious, especially in young children. In addition, biotin treatment can potentially interfere with other streptavidin—biotin immunoassays. This potential interference with laboratory tests is usually not referenced to the clinician in laboratory reports (Kummer, N Engl J Med 2106).
    Recommended Intake: The AI for biotin is 8 mcg for children 1 to 3, 12 mcg for those 4 to 8, and 20 mcg for those 9 to 13. For individuals 14 years to 18, the AI is 25 mcg and for those 19 and older it is 30 mcg. However, the AI increases to 35 mcg for women who are breast-feeding.
    Upper Limit: No UL has been established for biotin.

    See the Encyclopedia article on Biotin for more information about clinical use.

  • Folate (Folic Acid, Folacin, Metafolin, Quatrefolic, or B-9) plays an important role in cell division and adequate intake can reduce the risk of heart disease and lessen the risk of developing certain cancers. It also reduces the risk of spina bifida in offspring (a leading cause of childhood paralysis) when consumed by pregnant women. Folate may also reduce the chance of childhood leukemia and other birth defects in offspring. For example, the risks of having a child with autistic disorder or severe language delay were, respectively, 39% and 45% lower among mothers in Norway using folic acid supplements (400 mcg/day) around the time of conception (4 weeks before to 8 weeks after the start of pregnancy) than among mothers who did not take a folic acid supplement (Suren, JAMA 2013; Roth JAMA 2011). Good sources of folate include dark green leafy vegetables and oranges (see the USDA's list of folate content of various foods). Folic acid, a synthetic folate, is more stable and absorbed 1.67 times as well as natural folate. Folate deficiency has decreased since mandatory folic acid fortification of enriched cereal grain products began in 1998. Less than 1% of Americans are now deficient in folate, according the CDC. Sharing folic acid's advantages are two other synthetic products, Metafolin and Quatrefolic, which were accepted as sources of folate by the FDA in 2001 and 2010, respectively. Each contains the same active compound (L-5-methylfolate) as is created in the body from folate and folic acid, but stabilized with either calcium (as in Metafolin) or glucosamine (as in Quatrefolic). They are somewhat more bioavailable than folic acid in short-term use. These forms have been promoted for use by people with common genetic mutations affecting the MTHFR enzyme, however, even people with these mutations appear able to use folic acid, although perhaps with less efficiency (Prinz-Langenohl, BJP 2008). Metafolin and Quatrefolic contain a very small amount of D-5-methylfolate, which is not a natural compound and may, hypothetically, reduce the bioavailability of L-5-methylfolate (Willems, Br J Pharmacol 2004).
    Recommended Intake:The RDAs for folate are based on intake from regular food sources. If you are relying on supplements or fortified foods (with folic acid or forms of L-5-methylfolate) to reach the RDA, you need only 60% of the amount listed in the following RDAs: 150 mcg for children 1 to 3, 200 mcg for children 4 to 8, and 300 mcg for children 9 to 13. For individuals 14 years and older the RDA is 400 mcg. However, the RDA for pregnant women is 600 mcg, and for lactating women it is 500 mcg. In view of its importance to developing fetuses during the first few weeks after conception, it is recommended that all women capable of becoming pregnant consume 400 mcg of folic acid from supplements or fortified foods in addition to intake of folate from a varied diet. To treat folate deficiency, 250 - 1000 mcg per day is used, although higher amounts (1 to 5 mg) may be appropriate in cases of severe deficiency. A large study in adults being treated for high-blood pressure in China found that adding 800 mcg of folic acid to their anti-hypertensive medication regimen significantly reduced the risk of stroke. Over 4.5 years, 2.7% of those who received folic acid experienced a stroke compared to 3.4% of those who didn't receive folic acid (Huo, JAMA 2015). It should be noted that the study population began the study relatively low in folate (blood levels averaging 8.1 ng/mL) and the observed benefit may only occur among people with low folate levels. In fact, among participants who started the study with the lowest levels of folate (averaging just 5.6 ng/mL) and didn't receive folic acid, 4.6% experienced strokes. Unlike in the U.S., where folic acid is added to grain products (and adult folate levels average 10 to 12 ng/mL), folic acid is not added to grain products in China. Similarly, a study among adults in China with low blood levels of folate (about 5.5 ng/mL) and mild to moderate Alzheimer's disease found that those who took 1,250 mcg of folic acid in addition to their standard medication (donepezil [Aricept]) daily for six months had less inflammation and maintained slightly better cognitive function over the course of the study compared to those who only took the medication (Chen, Mediators Inflamm 2016). Those who took folic acid developed average blood folate levels similar to that U.S. adults (10 to 12 ng/mL, as noted above), so it is not certain that similar supplementation would be beneficial to people with blood folate levels which are already adequate.
    Upper Limit: Prolonged intake of excessive folic acid can cause kidney damage and can complicate the diagnosis of vitamin B-12 deficiency because folic acid supplementation can mask a symptom of vitamin B-12 deficiency known as macrocytosis (which affects red blood cells and is seen in blood tests). A potential benefit of L-5-methylfolate forms over folic acid is that they may not mask vitamin B-12 deficiency. A high folate level in the blood combined with low B-12 has been also associated higher risk of cognitive impairment in older individuals; although, when B-12 levels are normal, high folate levels may be protective against cognitive impairment (Morris, Am J Clin Nutr 2007).  Even when B-12 levels are normal, high intake of folate dramatically increases the risk of peripheral neuropathy (often causing reduced sensation in the feet) in elderly people who have a common genetic variant. People with this variant (a change in the TCN2 gene), which is found in about one-quarter of older Americans, are no more likely than others to experience this problem if their daily folate intake is below 800 mcg, but when above 800 mcg (typically due to multivitamin use), the odds of peripheral neuropathy are seven-fold higher compared to those without the variant. (Sawaengsri, Am J Clin Nutr 2016). The UL for folate applies only to that consumed from synthetic forms in supplements and fortified foods and is 300 mcg for children 1 to 3, 400 mcg for those 4 to 8, 600 mcg for those 9 to 13, and 800 mcg for those 14 to 18. For individuals 19 years and older the UL is 1,000 mcg. In addition, folic acid at 1,000 mcg per day from a supplement has been associated with a more than doubling of the risk of prostate cancer, although folate from the dietary sources (i.e., food) was not found to increase the risk (Figueiredo, 2009). While folate may reduce the risk of cancers, most notably colorectal cancer, there is growing concern that too much folic acid from supplementation (including fortified foods) may promote cancer in individuals with pre-cancerous or cancerous tumors (Mason, 2009 ). A study in Chile, for example, showed an increase in colorectal cancer after that country began to fortify wheat flour with folic acid and a similar association has been noted in other countries (Hirsch, 2009). However, a more recently published analysis of results from a cancer prevention study in the U.S. did not find a significant association between folic acid intake and colorectal cancer. In fact, the study found a 19% reduction in the risk of colon cancer in people with the highest total folate intake (i.e., combined intake of natural folate and folic acid) compared to those with the lowest intake (Stevens, Gastroenterlolgy 2011). Although multivitamin supplementation (3 to 5 times a week) in pregnant women is associated with a reduced risk of autism in a child, excessively high blood levels of folate (>59 nmol/L) in pregnant women is associated with an approximate twofold increased risk of autism in a child according to one observational study (Raghavan, International Meeting for Autism Research 2016). The study also found that for pregnant women who had excessive blood levels of both folate and vitamin B-12, the risk was 17.6 times greater.

     A study in Canada (which, like the U.S., requires folic acid fortification of certain grain-based products -- adding about 100 mcg of folic acid to the average adult daily diet) found that 10-18% of supplement users exceeded the UL for folate and 20-52% had elevated folate levels in their blood cells. The report stressed the need for people to be aware of the potential risks of folate overconsumption. Excluding supplements, average dietary folate intake was about 450 mcg, which meets the adult requirement of 400 mcg, although it was noted that about 40% of women over 70 years obtained less than the requirement -- averaging about 350 mcg (Mudryj, Br J Nutr 2016). Keep in mind that synthetic forms of folate, such as folic acid in supplements and fortified foods, provide 167% as much absorbable folate as folate naturally found in foods, e.g., if you are short 100 mcg of folate in your diet, you can satisfy that with just 60 mcg of folic acid from a supplement. Unfortunately, most supplement labels don't make this clear and will not be required to until 2018/19. If a label says "Folic Acid 400 mcg, 100% DV" it actually provides the equivalent of 667 mcg of natural folate and 167% of the current DV.

    See the Encyclopedia article on Folate for more information about clinical use.

  • Cobalamin (B-12) deficiency can cause anemia, irreversible nerve damage, and low sperm count. Symptoms can include fatigue, tingling in the arms and legs, weakness loss of balance or trouble walking, which could potentially lead to falls (Briani, Nutrients 2013; Jansen Ned Tijdschr Geneeskd 2013). Blood levels below 200 pg/mL are a sign of deficiency, although older adults may have symptoms at blood levels of 200 — 500 pg/mL (NIH 2014). Higher levels of B-12 intake and in the blood have also been associated with minimizing cognitive decline in older individuals. Vitamin B-12 is found in abundant quantity in meats and is also plentiful in poultry and fish. For vegetarians, fortified cereals, milk and yogurt may provide sufficient B-12. However, unless fortified, plant-based foods are not good sources of B-12. A healthful diet should meet the vitamin B-12 RDAs, but supplementation is often needed for strict vegetarians, alcohol and drug abusers, people recovering from surgery or burns, or those with bowel or pancreatic cancer. According to the CDC, 2% of Americans are deficient in B-12, including 4% of older adults. Deficiency may also occur in people with low stomach acidity, such as older individuals or those taking medications that reduce stomach acid, because stomach acid is necessary to allow absorption of vitamin B-12 from foods. In fact, a large study in adults found that the chance of being B-12 deficient was 65% higher among people taking a proton-pump inhibitor (e.g. Prevacid, Prilosec) and 25% higher among those taking a H2-blocker (e.g., Pepcid, Zantac) than among people not taking these drugs. Furthermore, the risk of B-12 deficiency was 95% higher among people averaging more than 1.5 of these pills daily compared to those averaging less than 0.75 pill. The association was particularly strong among younger adults (under 30), who are otherwise less likely to be deficient in B-12 (Lam, JAMA 2013). The purified vitamin B-12 found in supplements does not require stomach acid for absorption. Consequently, it is advisable for people over 50 years of age as well as those taking acid-blocking medications to meet their RDA by consuming foods fortified with purified vitamin B-12 or by taking a dietary supplement. The most common form of B-12 in supplements is cyanocobalamin. Although this form includes a cyanide molecule, it is very safe -- even at a very high dose (5,000 mcg), it would provide about a thousand times less cyanide than is toxic, and the cyanide is excreted in the urine (an exception: the ability to excrete cyanide in the urine can be compromised in people with kidney failure and therefore cyanocobalamin is not advisable in such individuals) (Spence Clin Chem Lab Med 2013). B-12 is also available in supplements as methylcobalamin and hydroxocobalamin. There is no clinical evidence indicating differences in the absorption, bioavailability, or clinical efficacy among these three forms, although cyanocobalamin may be preferable as it is more stable and less expensive (Obeid, Mol Nutr Food Res 2015). Some websites claim methylcobalamin to be superior because it is the "active" form of B-12 (the form utilized in the body). However, it's important to note that all forms are converted into the common intermediate cobalamin which, in turn, transfers into the active forms of B-12 used by the body (methylcobalamin and adenosylcobalamin). For people with very rare genetic defects in cobalamin metabolism (typically diagnosed in the first year of life), the hydroxocobalamin form may be better utilized (Obeid, Mol Nutr Food Res 2015).
    Recommended Intake: The RDA is 0.9 mcg for children 1 to 3, 1.2 mcg for those 4 to 8, and 1.8 mcg for those 9 to 13. For individuals 14 years and older the RDA is 2.4 mcg. However, the RDA for pregnant women is 2.6 mcg and for lactating women it is 2.8 mcg. A dose of 500 mcg given either sublingually or orally has been shown to be equally effective in correcting early B-12 deficiency, although higher doses (1,000 to 5,000 mcg orally) have been used to treat more advanced deficiency (Sharabi, Br J Clin Pharmacol 2003). High doses of vitamin B-12 (about 400 mcg per day) have also been proposed for helping to prevent heart disease. Vitamin B-12 in far higher dosages has also been proposed for the treatment of other conditions including asthma, fatigue, and male infertility, but there is no reliable evidence that it is effective.
     Upper Limit: No UL has been established for vitamin B-12. This appears to be a very safe ingredient for most people. However, as noted in Concerns and Cautions below, a B-complex supplement providing 1,000 mcg of B-12 daily was found to increase the risk of heart attack, stroke and death in people with type 1 or type 2 diabetes who had advanced kidney disease. A study in Italy found that malnourished people admitted to hospitals who had elevated B-12 blood levels (>1,000 pg/mL) were twice as likely to die in the hospital as similar patients whose B-12 levels were not elevated. B-12 levels can be affected by disease, but the association in this study was found to be independent of kidney and liver function, inflammation, and degree of weight loss. While this does not prove a cause-and-effect relationship, the researchers cautioned about inappropriate B-12 supplementation (Cappello, Nutrients 2017). In addition, B-12 doses of 20 mcg per day or higher (including intramuscular injection of 1,000 mcg of B-12) have been reported to cause outbreaks of acne and rosacea in some people (Jansen, J Eur Acad Dermatol Venereol 2001; Sherertz, Cutis 1991). The likely mechanism for this, as demonstrated in a series of experiments, is that oversupply of B-12 in some people causes a common and usually harmless skin bacteria, Propionibacterium acnes, to overproduce an inflammatory protein which leads to pimples on the skin (Kang, Sci Tranl Med 2015). Although rare, there have been reports of possible allergic reaction to vitamin B12 supplementation (Am Acad Asth Immunol 2013, Ask the Expert). In pregnant women, excessive blood levels of vitamin B-12 (>600 pmol/L) were associated with a 3X risk of autism in offspring and this increased to 17.6X when blood levels of both folate and vitamin B-12 were excessive (Raghavan, International Meeting for Autism Research 2016).

    See the Encyclopedia article on Vitamin B-12 for more information about clinical use.

    Concerns and Cautions: Try to avoid taking too much of any B vitamin. Check the ULs listed above and, if you need to take a product with vitamins exceeding the ULs, do so under a physician's supervision and with awareness of potential side effects. For example, a recent large study of diabetes patients (type 1 and type 2) with advanced nephropathy (kidney disease) given high-dose B vitamins (folic acid - 2,500 mcg, B-6 - 25 mg, and B-12 - 1,000 mcg daily) showed a worsening of kidney function and doubling of the risk of myocardial infarction (MI), stroke, and death in the B-vitamin group compared to the placebo group. The study was designed with the expectation that the vitamins would have the opposite effect because of the ability of B vitamins to lower homocysteine levels, which did decrease. (House, JAMA 2010).

    Be aware that certain B vitamins can interact with other drugs and supplements as noted above.

    To further assist consumers, ConsumerLab.com licenses its flask-shaped CL Seal of Approved Quality (see The CL Seal) to manufacturers for use on labels of products that have passed its testing. ConsumerLab.com will periodically re-evaluate these products to ensure their compliance with ConsumerLab.com's standards.

    Information on this site is provided for informational purposes only. It is not an endorsement of any product nor it is it meant to substitute for the advice provided by physicians or other healthcare professionals. The information contained herein should not be used for diagnosing or treating a health problem or disease.


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