If you’re already taking a high-potency B-complex or multivitamin supplement, you may be set in terms of satisfying your requirements. I define a high-potency supplement as one containing 20 mg or more of the major B vitamins, such as B1, B2, B3, and B6. Although different companies’ formulations vary, the amounts of “minor” B vitamins tend to fall in place behind the major Bs. That said, some people may need extra amounts of individual B vitamins.

Ten B vitamins make up this family of essential nutrients. Two others (inositol and para-aminobenzoic acid (PABA)) are sometimes grouped with the Bs, though they technically are not part of the family.

Vitamin B1

Also known as thiamin, vitamin B1 serves as the “throttle” that sets in motion our cells’ energy-generating Krebs cycle. Add up the energy created by 70 trillion cells in your body, and you’ve got the power to get you through day-to-day life; but without B1, the cells will not be able to produce optimal amounts of energy. Some drugs, such as loop diuretics, deplete vitamin B1 and can induce a deficiency. So can excessive intake of alcohol.

Eating lots of sugars and simple carbohydrates also depletes vitamin B1. The breakdown of carbohydrates requires a family of enzymes called dehydrogenases, and vitamin B1 is required to make dehydrogenases. With the consumption of large amounts of refined carbohydrates—breads, pizzas, pastas, bagels, cereals, and muffins—your requirements for the vitamin increase. But those carbs provide little if any vitamin B1, so a functional deficiency of the vitamin develops. The solution? Try reducing your carbohydrate consumption, increasing your vitamin B1 intake, or both.

Beneficial Benfotiamine

Benfotiamine is a fat-soluble derivative of thiamine (vitamin B1). It is significantly more bioavailable than thiamine and it fulfills the same roles as thiamine in the body. Benfotiamine is also a potent antioxidant and anti-inflammatory. Because benfotiamine can inhibit major pathways associated with the vascular damage caused by high blood sugar, including the formation of advanced glycation end products (AGEs), it has been shown to prevent diabetic complications such as neuropathy and retinopathy.^1 2 3 4 In animal models of Alzheimer’s Disease, benfotiamine is neuroprotective and decreases tau protein and neurofibrillary tangles in the brain (which impair communication between neurons).^{5 6} In small, preliminary human studies, long term use of benfotiamine (12 to 18 months) prevented a worsening of cognitive scores in people with mild cognitive impairment or mild Alzheimer’s Disease. ^{7 8}  Doses of benfotiamine used in studies range from 300 to 600 mg/day and appear to be exceptionally safe.  

Vitamin B2

Known as riboflavin, this vitamin forms the core of flavin adenine dinucleotide (FAD), one of the biochemicals that sits at the heart of energy production. FAD-dependent biochemical reactions break down carbs, fats, and sugars for energy.

Some researchers believe that migraine headaches may be related to low energy production in brain cells. A team of German researchers treated 23 men and women who had been experiencing frequent migraine headaches. The patients took 400 mg of vitamin B2 daily for six months, with clinical assessments after three and six months. The frequency of migraine headaches decreased by about half, as did the length of the headaches. A separate study found that almost two-thirds of 55 patients benefited from at least a 50 percent reduction in migraine headaches after taking the vitamin. Note: vitamin B2 will turn your urine yellow, but is not harmful; the molecule just happens to have a yellow color.

Vitamin B3

This vitamin, commonly known as niacin, forms the core of nicotinamide adenine dinucleotide (NAD), which functions in tandem with FAD to generate energy. The body also uses NAD to make the highly specialized enzymes, poly (ADP-ribose) polymerase, which repairs DNA damage, and sirtuins (specifically SIRT1 and SIRT3), which act as master metabolism regulators, influencing everything from insulin sensitivity and healthy cholesterol levels, to lifespan.⁹ Without sufficient vitamin B3 to make these enzymes, cells cannot repair DNA damage from toxins (thereby increasing the risk of cancer), nor can they activate enzymes that have a positive influence on a wide variety of metabolic functions.

In the early 1950s, the late Abram Hoffer, M.D., Ph.D., and his colleagues theorized that a byproduct of adrenaline caused delusions and hallucinations in the schizophrenic—and that a combination of vitamins B3 and C might break down the problematic chemical. Hoffer conducted the first double-blind study in psychiatry, reporting that the vitamin combination (3,000 mg of each daily) led to recoveries among people with recent-onset schizophrenia. That study was published in the prestigious Bulletin of the Menninger Clinic.

In 1955, Hoffer also demonstrated that the niacin form of vitamin B3 could significantly lower blood cholesterol levels. Vitamin B3 comes in three forms as a supplement—niacin, niacinamide and nicotinamide riboside. Note: The niacin form temporarily dilates blood vessels and causes a flushing sensation that feels like a skin allergy. Some people tolerate the niacin flush, whereas others find it uncomfortable, but it eases after about one hour. The niacinamide form doesn’t cause a flush, but does not have a lowering effect on cholesterol levels. Nicotinamide ribose does not cause a flush, has beneficial effects on cholesterol levels, and appears to be the most potent form of B3 for enhancing cellular NAD levels.¹⁰ New research into nicotinamide riboside suggests it may improve insulin sensitivity, enhance energy production, revitalize stem cells and prevent the production of beta-amyloid (proteins found in the plaques that form in the brains of Alzheimer’s patients).^{11 12 13}

Vitamin B6

Also known as pyridoxine and pyridoxyl-5-phosphate, vitamin B6 works with folic acid and vitamin B12 in a group of important chemical reactions known as methylation. Methylation creates methyl groups, consisting of a carbon and three hydrogen atoms, which promote a variety of chemical reactions involved in the production of serotonin and other mood-enhancing neurotransmitters. In an analysis of nine studies in which vitamin B6 was used to treat premenstrual syndrome (PMS), researchers reported that the vitamin reduced overall symptoms by more than half.

Still other research has shown that vitamin B6 can ease symptoms of carpal tunnel syndrome (CTS), a repetitive-motion disorder that affects the wrists. The repetitive motion stresses biochemicals that depend on vitamin B6 and sometimes other B vitamins. Taking 100 to 200 mg of vitamin B6, plus a B-complex supplement, can often resolve CTS in about three months.

Coenzymated B-Vitamins

In order for the body to be able to use many of the B vitamins we obtain through our food and supplements, they must first be converted by the liver into their “active” form. In their active, also known as “coenzymated” form, the B vitamins are bound to the necessary amino acid or mineral cofactor and are ready to be utilized by the body. 

Some individuals, due to poor liver function, digestive disturbances, nutrient deficiencies or age may not be able to effectively make the conversion from the inactive to active forms. 

There are also gene variations that can interfere with the body’s ability to convert certain B vitamins into their usable forms. One such variation occurs in people with a common genetic polymorphism, or mutation, in the gene that is responsible for folate metabolism. This gene is called methylenetetrahydrofolate reductase gene (or MTHFR).  

The MTHFR gene is involved in producing an enzyme of the same name that is responsible for a very important biochemical process in the body called methylation. Methylation is essential in every cell of the body for repair, detoxification, neurotransmitter production, and immune system function. Methylation is also necessary for converting folic acid and vitamin B12 into their active forms. 

People with this genetic variation are unable to effectively use the folic acid and non-methyl B12 form of these nutrients found in fortified foods and dietary supplements. Instead, people with this genetic variant require the form that has already been methylated, the active form of folate (L-methyl-folate or L-5-MTHF (methyltetrahydrofolate) and the form of B12 called methylcobalamin.

Adequate levels of these nutrients are needed to optimize methylation of other compounds, which in turn influences brain function (mood, memory, cognition), immune system function, detoxification, and the ability to obtain optimal health. (Doctors practicing functional medicine and Naturopathic doctors offer genetic testing to determine if a mutation in the MTHFR gene exists.)

In general, choosing B vitamin supplements that are already coenzymated delivers the active forms, bypassing the need for them to be converted by the body. The active forms are immediately available to go to work supporting the multitude of biochemical reactions the B vitamins are involved in every day.

Vitamin B12

One-third of seniors suffer from atrophic gastritis, a condition that interferes with vitamin B12 absorption. Acid-blocking drugs, antibiotics, and oral contraceptives also interfere with the vitamin. Nitrous oxide, one of the drugs given during anesthesia, can completely destroy a person’s vitamin B12 reserves. Deficiencies can sometimes mimic symptoms of severe brain fog and even Alzheimer’s disease. Because vitamin B12 is relatively inexpensive, everyone who is suspected of having Alzheimer’s or another type of dementia should have their levels of B12 tested.

Low levels of vitamin B12 can increase gene damage, which could theoretically accelerate aging and the risk of cancer. Michael Fenech, Ph.D., a researcher at Australia's Commonwealth Scientific and Industrial Research Organization, found that supplemental B12 and folic acid could reduce gene damage. Meanwhile, another study found that people who took vitamin B12 supplements had relatively long telomeres (the protective tips of chromosomes, which contain genes), compared with people who did not take the vitamin.

Vitamin B12 supplements come in several forms. The most common is cyanocobalamin, but many people consider hydroxycobalamin and methylcobalamin to be more natural. I prefer the sublingual forms (under the tongue), which bypass absorption problems in the gut. Consider taking 100 to 1,000 mcg daily.

Folic Acid

Your body requires only about 1/70,000^th of an ounce of folic acid daily, but this tiny amount is put to exceptional use in every cell of the body. Folic acid is the main contributor to “one-carbon metabolism,” a crucial step in making new DNA, which in turn is needed to make new cells for growth and healing. Methyl groups (see B6) depend on folic acid, and they regulate the activities of genes. For example, methyl groups turn off many cancer-promoting genes.

A growing fetus has enormous requirements for folic acid. If a woman does not consume sufficient folic acid around the time of conception, her baby has a high risk of being born with a serious birth defect, such as spina bifida and cleft lip.

In addition, a lack of folic acid (sometimes in combination with low vitamin B6 and B12) increases blood levels of homocysteine, a substance that boosts the risk of heart disease, stroke, and Alzheimer’s disease. In one study, folic acid supplements (800 mcg daily) slowed hearing loss in middle-age and older people by almost one-half. The same researchers also reported that folic acid improved mental function. Some research has shown that folic acid supplements can enhance the benefits of anti-depressant drugs.

The natural form of folic acid in leafy green vegetables is folate. In supplements, you’ll find folic acid and methylfolate.

Pantothenic Acid

If you’re feeling stressed all the time, consider adding some extra pantothenic acid and vitamin C to your B-complex or multivitamin. Pantothenic acid and vitamin C support your body’s production of adrenal hormones, your natural buffers against stress. Your adrenal hormones also have anti-inflammatory benefits, so consider following the same advice if you have aches and pains.

Biotin

This little-known B vitamin activates some of the genes involved in metabolizing blood sugar, protein, and fat; it’s especially important for people with prediabetes or type-2 diabetes. You need biotin to make and use glucokinase, an enzyme that functions as a “glucose sensor” in the pancreas. When blood sugar levels rise, glucokinase signals the pancreas to secrete more insulin. Without adequate biotin, the body cannot make glycokinase. People with diabetes and other forms of glucose tolerance are often deficient in biotin, and blood sugar disorders are often helped with large amounts of biotin. Some supplements combine biotin with either chromium or R-lipoic acid to help lower blood sugar.

Biotin has two other important benefits. First, large amounts (3,000 to 5,000 mcg daily) can often help lower blood levels of triglycerides, a risk factor for heart disease. It has also been used to treat brittle fingernails. In a study of 32 women, supplemental biotin increased nail thickness by 25 percent and reduced splitting.

Choline

Officially recognized as an essential nutrient in 1998, choline is found in all cell membranes, where it helps communicate external information to the cell nucleus. It’s a precursor to acetylcholine and phosphatidylcholine, needed for normal brain development and function. Acetylcholine, a neurotransmitter, is required for memory, and many of the drugs used to treat Alzheimer’s disease work by blocking the brain’s breakdown of choline.

In a study of people receiving intravenous nutrition, researchers found that the addition of choline improved both visual and word recall. Another study found that choline supplements improved memory in people who had been considered poor learners. And two well-controlled studies found that taking 25 mg of phosphatidylcholine for six months led to modest improvements in memory among people with early Alzheimer’s disease.

You’ll find choline as a standalone supplement, as well as in phosphatidylcholine and lecithin. Lecithin is about 13 percent choline by weight.

To B or not to B?

Other supplements may garner bolder headlines, while the B-complex vitamins may seem a bit ho-hum. But don’t ever underestimate their importance to your health.

While B Vitamins are often called by their number, they each have a corresponding name. The chart below can help you decipher terms you may come across.

References

1. Hammes, H. P., Du, X., Edelstein, D., Taguchi, T., Matsumura, T., Ju, Q., Lin, J., Bierhaus, A., Nawroth, P., Hannak, D., Neumaier, M., Bergfeld, R., Giardino, I., & Brownlee, M. (2003). Benfotiamine blocks three major pathways of hyperglycemic damage and prevents experimental diabetic retinopathy. Nature medicine, 9(3), 294–299. https://doi.org/10.1038/nm834
2. Winkler, G., Pál, B., Nagybéganyi, E., Ory, I., Porochnavec, M., & Kempler, P. (1999). Effectiveness of different benfotiamine dosage regimens in the treatment of painful diabetic neuropathy. Arzneimittel-Forschung, 49(3), 220–224. https://doi.org/10.1055/s-0031-1300405
3. Haupt, E., Ledermann, H., & Köpcke, W. (2005). Benfotiamine in the treatment of diabetic polyneuropathy--a three-week randomized, controlled pilot study (BEDIP study). International journal of clinical pharmacology and therapeutics, 43(2), 71–77. https://doi.org/10.5414/cpp43071
4. Stracke, H., Gaus, W., Achenbach, U., Federlin, K., & Bretzel, R. G. (2008). Benfotiamine in diabeticpolyneuropathy (BENDIP): results of a randomised, double blind, placebo-controlled clinical study. Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association, 116(10), 600–605. https://doi.org/10.1055/s-2008-1065351
5. Tapias, V., Jainuddin, S., Ahuja, M., Stack, C., Elipenahli, C., Vignisse, J., Gerges, M., Starkova, N., Xu, H., Starkov, A.A., Bettendorff, L., Hushpulian, D.M., Smirnova, N.A., Gazaryan, I.G., Kaidery, N.A., Wakade, S., Calingasan, N.Y., Thomas, B., Gibson, G.E., Dumont, M., Beal, M.F. (2018). Benfotiamine treatment activates the Nrf2/ARE pathway and is neuroprotective in a transgenic mouse model of tauopathy. Hum Mol Genet, 27(16), 2874-2892. doi: 10.1093/hmg/ddy201
6. Pan, X., Gong, N., Zhao, J., Yu, Z., Gu, F., Chen, J., Sun, X., Zhao, L., Yu, M., Xy, Z., Dong, W., Qin, Y., Fei, G., Zhong, C., Xu, T.L. (2010). Powerful beneficial effects of benfotiamine on cognitive impairment and β-amyloid deposition in amyloid precursor protein/presenilin-1 transgenic mice. Brain, 133(5), 1342-1351. https://doi.org/10.1093/brain/awq069
7. Gibson, G. E., Luchsinger, J. A., Cirio, R., Chen, H., Franchino-Elder, J., Hirsch, J. A., Bettendorff, L., Chen, Z., Flowers, S. A., Gerber, L. M., Grandville, T., Schupf, N., Xu, H., Stern, Y., Habeck, C., Jordan, B., & Fonzetti, P. (2020). Benfotiamine and Cognitive Decline in Alzheimer's Disease: Results of a Randomized Placebo-Controlled Phase IIa Clinical Trial. Journal of Alzheimer's disease : JAD, 78(3), 989–1010. https://doi.org/10.3233/JAD-200896
8. Pan, X., Chen, Z., Fei, G., Pan, S., Bao, W., Ren, S., Guan, Y., & Zhong, C. (2016). Long-Term Cognitive Improvement After Benfotiamine Administration in Patients with Alzheimer's Disease. Neuroscience bulletin, 32(6), 591–596. https://doi.org/10.1007/s12264-016-0067-0
9. Cantó C, Houtkooper RH, Pirinen E, Youn, D.Y., Oosterveer, MH., Cen, Y., Fernandez-Marcos, P.J., Yamamoto, H., Andreux, P.A., Cettour-Rose, P., Gademann, K., Rinsch, C., Schoonjans, K., Sauve, A.A., Auwerx, J. (2012). The NAD+ precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet induced obesity. Cell Metabolism, 15(6), 838-847. https://doi.org/10.1016/j.cmet.2012.04.022
10. Mehmel, M., Jovanović, N., & Spitz, U. (2020). Nicotinamide Riboside-The Current State of Research and Therapeutic Uses. Nutrients, 12(6), 1616. https://doi.org/10.3390/nu12061616
11. Gong, B., Pan, Y., Vempati, P., Zhao, W., Knable, L., Ho, L., Wang, J., Sastre, M., Ono, K., Sauve, A. A., & Pasinetti, G. M. (2013). Nicotinamide riboside restores cognition through an upregulation of proliferator-activated receptor-γ coactivator 1α regulated β-secretase 1 degradation and mitochondrial gene expression in Alzheimer's mouse models. Neurobiology of aging, 34(6), 1581–1588. https://doi.org/10.1016/j.neurobiolaging.2012.12.005
12. Cantó, C., Houtkooper, R. H., Pirinen, E., Youn, D. Y., Oosterveer, M. H., Cen, Y., Fernandez-Marcos, P. J., Yamamoto, H., Andreux, P. A., Cettour-Rose, P., Gademann, K., Rinsch, C., Schoonjans, K., Sauve, A. A., & Auwerx, J. (2012). The NAD(+) precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet-induced obesity. Cell metabolism, 15(6), 838–847. https://doi.org/10.1016/j.cmet.2012.04.022
13. Ecole Pólytechnique Fédérale de Lausanne. Vitamin stops the aging process of organs: Nicotinamide riboside rejuvenates stem cells, allowing better regeneration processes in aged mice. ScienceDaily. April 28, 2016. Available at: https://www.sciencedaily.com/releases/2016/04/160428152124.htm

Side Bar References:

• Lynch, B. (2019, June 27). L-Methylfolate, Methylfolate, 5-MTHF, L-5-MTHF. Why many variations? MTHFR.Net. https://mthfr.net/l-methylfolate-methylfolate-5-mthf/2012/04/05/
• Carnahan, J. (n.d.). MTHFR gene mutation. . . What’s the big deal about Methylation? http://doccarnahan.blogspot.com/2013/05/mthfr-gene-mutation-whats-big-deal.html
• [PDF] Improving Patient Outcomes: Identifying Common Methylation Polymorphisms by Benjamin Lynch, ND President & CEO - free download PDF. (n.d.). https://silo.tips/download/improving-patient-outcomes-identifyig-common-methylation-polymorphisms-by-benja