Forty Percent of Americans May Have Less Than Optimal B-12 Levels—Are You One of Them?

Feeling tired, stressed, and moody lately? Blindsided by the midafternoon energy slump, stocking up on double espresso and energy drinks? Skipping your exercise routine and pressing the snooze alarm in the morning? You’re not alone. In fact, ordinary tiredness is the most common complaint general practitioners hear from their patients[1] and more women than men report it.[2]

Although there are many reasons for ‘garden variety’ fatigue, one reason can be suboptimal levels of B vitamins. B vitamins—thiamine (B-1), riboflavin (B-2), niacin (B-3), pantothenic acid (B-5), pyridoxine (B-6), B-12, biotin, and folate (B-9)—are directly involved in energy production. Of particular importance is vitamin B-12, a water soluble vitamin that helps our body manufacture DNA for new cells, is critical for building healthy red blood cells, and helps convert our food into energy. Dr. Roxanne Sukol, Medical Director of Cleveland Clinic’s Wellness Enterprise, told Time Magazine in 2016 that: “B vitamins are essential for proper cellular respiration.” A deficiency of B-12 can affect everything from energy to mood to concentration, she explained to Time Magazine.

Research suggests that somewhere between 15-40% of Americans have marginal vitamin B-12 status. In a famous study conducted in the year 2000, 3,000 men and women aged 26 to 83 were assessed, and 39% had B-12 in the “low normal” range–below 258 picomoles per liter.[3] The study’s lead author, Katherine Tucker, a nutritional epidemiologist at Tufts University in Boston, told the USDA that some people exhibit neurological symptoms at this range. “There is a question as to what the clinical cutoff for deficiency should be,” she told the USDA. The study also found that an astonishing 9% of individuals were actually outright deficient. “I think there is a lot of undetected vitamin B-12 deficiency out there,” she explained to the USDA. There can be many reasons for low B-12 levels, ranging from a vegetarian diet to digestive issues, excessive alcohol consumption, or regular consumption of antacids. In fact, because as we age our stomach acid production declines, it is recommended that all Americans over age 50 take 25-100 mcg/day of supplemental B-12.

Your liver can convert B-12 to an active, methylated form, known as Methyl B-12, or methylcobalamin, which supports brain and nerve health. Methylcobalamin is also well known for its ability to keep a naturally occurring amino acid, homocysteine, in check. High homocysteine levels have been linked to cardiovascular disease and Alzheimer’s disease. Some individuals harbor genetic variations that inhibit their ability to transform vitamin B-12 methylcobalamin, but these variations are not reported in commercial tests, and require special genetic testing.[4]

Why Are B-12 Shots So Popular?

These days, everybody from general practitioners and internists to medical spas are offering B-12 injections for those who hope to boost their metabolism and increase their energy levels. It’s the “shot of champions”, according to Variety, and everyone from former Prime Minister Margaret Thatcher to celebrities like Charlize Theron have gotten injections of B-12.One doctor told Variety that she sees 30 patients a week who come in just for a B-12 shot. A standard shot contains 1,000 micrograms of B-12, which is 400 times more than the recommended daily allowance.

But is a shot necessary? Though injections can be effective by bypassing digestion, and low stomach acid, they can be painful and expensive, and are not always covered by health insurance. One study found that the annual cost of vitamin B-12 shots averaged $145.88 per person and could total up to $25 million over 5 years. A single shot can be around $80 at some offices.

Liposomal B-12—An Optimal Solution?

A liposomal spray formulation of bioactive, bioavailable methyl B-12 can offer rapid uptake and high absorption because small liposomal vesicles are absorbed intraorally, bypassing digestive issues, stomach acid, and impaired conversion of B-12 to its active form. A liposomal formulation may offer the same immediate effect as a shot.

The effectiveness of liposomal formulations has been demonstrated in a line of cells called Caco2, originally derived from the human intestinal lining, and which are a gold standard for studying the ability of molecules to cross the gut wall. Data on Caco2 cells correlate well with human data for absorption of many different molecules.[5] In one study on Caco2 cells, smaller liposomes showed dramatically higher uptake at fifteen minutes, and even higher uptake at one hour. The liposomes were stained with a bright orange-red dye in order to observe the pattern of their flow, and the smallest sizes (50 and 64 nanometers) showed “considerable increase in uptakes,” according to the scientists. Yet without liposomes, there was virtually no absorption at all.[6] Another study confirmed that size of liposomes is critical: large liposomes with diameters more than 105 nanometers did not penetrate through deeper skin layers, while smaller liposomes showed enhanced penetration, allowing them pass rapidly through the deeper skin layers without rupturing.[7] These findings suggest that nanoscale liposomes with well-controlled size and minimal size variance are excellent vehicles for transdermal delivery of functional nanoparticle drugs.

Studies on liposomal B-12 show faster absorption and higher plasma levels.[8] A recent cell culture study modeled on the Caco2 studies above, and performed by Quicksilver ScientificTM, looked at intraoral absorption and uptake of liposomal Methyl B-12. Regular Methyl B-12 was compared to liposomal Methyl B-12 and to liposomal Methyl B-12 with specific enhancements and modifications to the surface of the liposome. A tiny, 53 nanometer liposome with surface modifications showed nearly triple the uptake and blood levels of Methyl B-12 compared to the other two formulations.[9] In general, liposomal molecules adhere well to cell membranes, and increase lymphatic uptake. They have been successful in improving oral bioavailability of many different compounds.[10] So next time you need an energy boost, you might consider a spritz not a shot–of liposomal B-12, that is.


References

[1]Sugarman JR, Berg AO. Evaluation of fatigue in a family practice. J Fam Pract 1984;19:643-47. View Abstract
[2]Elnicki DM, Shockcor WT, et al. Evaluating the complaint of fatigue in primary care: diagnoses and outcomes. Am J Med 1992;93:303–06 View Abstract
[3]Tucker KL, Rich S Plasma vitamin B-12 concentrations relate to intake source in the Framingham Offspring study J Clin Nutr. 2000 Feb;71(2):514-22. View Abstract
[4] Paul C, Brady DM. Comparative Bioavailability and Utilization of Particular Forms of B12 Supplements With Potential to Mitigate B12-related Genetic Polymorphisms. Integr Med (Encinitas). 2017 Feb;16(1):42-49. Review. View Abstract
[5] Angelis ID, Truco L et al. Caco-2 cells as a model for intestinal absorption. Curr Protoc Toxicol. 2011 Feb Chapter 20:Unit20.6. View Abstract
[6] Abhay A, Hood RR et al. Pharmacy-On-A-Chip: microfluidic synthesis of pegylated and folate receptor-targeted liposomes for drug delivery. 16th International Conference on Miniaturized Systems for Chemistry and Life SciencesOctober 28 – November 1, 2012, Okinawa, Japan View Full Paper
[7] Hood RR, Kendal EL et al. Microfluidic-Enabled Liposomes Elucidate Size-Dependent Transdermal Transport. PLOS March 21, 2014 View Abstract
[8] Sharabi A, Cohen E, Sulkes J. Replacement therapy for vitamin B12 deficiency: comparison between the sublingual and oral route. Br J Clin Pharmacol. 2003 Dec;56(6):635-8. View Full Paper
[9] Quicksilver Scientific, IntraOral liposomal methyl-B12 serum uptake trials, unpublished study
[10] Daeihamed M, Dadashzadeh S et al. Potential of Liposomes for Enhancement of Oral Drug Absorption. Curr Drug Deliv. 2017;14(2):289-303. View Abstract