More on Cyanocobalamin Safety/Toxicity

 

Cobalamin (vitamin B-12) is synthesized only by certain microbes (bacteria and archaeon), and five forms of vitamin B-12 have been found in foods, according to the British Journal of Nutrition: adenosylcobalamin and hydroxocobalamin are the predominant forms, and other forms found include methylcobalamin, cyanocobalamin, and sulphitocobalamin. Most of these forms are considered synthetic substances, with additional compounds subsequently bonded to the already-synthesized cobalamin.

Methylcobalamin is produced commercially from cyanocobalamin, which is initially produced by fermentation and conversion processes. Adenosylcobalamin is directly produced by bacteria, while methylcobalamin requires an additional process of stripping off the cyanide group (CN, a carbon and a nitrogen atom with a triple bond) and adding a methyl group (CH3). Fermentations producing cyanocobalamin, methylcobalamin, and adenosylcobalamin do not utilize genetically engineered bacteria. The cyanocobalamin form is safe, stable, and bioavailable, and has been used for the vast majority of public health studies over the past century.

The amount of cyanide in cyanocobalamin is trivial, less than in an almond or apple; cyanide tends to be ubiquitous in the food supply in extremely tiny amounts. Cyanide is also produced by our own cellular processes (no great surprise since it's simply a single carbon and nitrogen molecule bonded together), but is quickly absorbed into the bloodstream, converted into thiocyanate (a less toxic form), and excreted in the urine or converted to carbon dioxide and exhaled. 

In fact, the Institute of Medicine has not set an Upper Limit for vitamin B-12 because “no adverse effects have been associated with excess vitamin B-12 intake from food and supplements in healthy individuals” (and both supplementation and food fortification primarily use cyanocobalamin). That same IOM report features this quote: “the amount of cyanide in cyanocobalamin is considered to be physiologically insignificant.” It would take about 2,500 doses of 1,000 microgram cyanocobalamin tabs to approach a dangerous amount of cyanide.

The adenosylcobalamin form is predominant in foods as well as in the human body, whereas methylcobalamin is typically in the body at only half the amount of the adenosyl form. Both are coenzyme forms with separate enzyme systems, and both are needed by the body. Cyanocobalamin feeds both pathways and is an inexpensive, stable, safe, and effective form of vitamin B-12 that does not require genetically engineered bacteria to produce.

Is citric acid made from black mold?

Yes, but so what? That organism - Aspergillus niger - has been used to safely manufacture citric acid for about 100 years. It's also used to make most of the 'fungal enzymes' that are vegetarian-friendly. People consuming citric acid are not eating black mold; just as you're not eating bees when consuming honey. 

People worried about the fermentation process have failed to distinguish between the mold and its purified byproducts that have a long history of safe use.  https://link.springer.com/article/10.1007/s00253-002-1032-6  

The fungus produces materials outside of its body that can be easily isolated and purified, so people are not inhaling or consuming mold when they use a material produced by fermentation. In fact, companies using citric acid perform their normal microbiological screening to assure that there are not concerning levels of mold in that material..

The mold itself would release spores that would be toxic to inhale if it were growing in your house. It may be mildly allergenic if you were eating the actual mold. But that's not what we are exposed to or are consuming when we eat citric acid, which is widely distributed in the processed food chain and has an important role in acidifying and preserving many foods and beverages. Look at your labels!

Isolated Aspergillus-derived products, including citric acid, have been sold for about a century and are considered safe. These also include common plant-derived enzymes such as protease, amylase, and lipase that are not pancreas-derived.  https://fungalbiolbiotech.biomedcentral.com/articles/10.1186/s40694-018-0054-5 

"Microbial citric acid has high economic importance and widely used in beverage, food, detergents, cosmetics and pharmaceutical industries. The filamentous fungus Aspergillus niger is a work horse and important cell factory in industry for the production of citric acid."   https://pubmed.ncbi.nlm.nih.gov/33044884/

"Aspergillus niger has a long tradition of safe use in the production of enzymes and organic acids (Soares de Castro et al., 2015)."  https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/aspergillus-niger#:~:text=The%20Aspergillus%20produces%20different%20types,et%20al.%2C%202015).

 

Aluminum in chlorella and other foods

Aluminum is one of the most abundant elements on earth and is correspondingly present in both food and water supplies. It is not a toxic heavy metal and so it is not routinely tested in foods or other raw materials, but the reported levels in chlorella are still low compared to common produce and other food staples; and chlorella’s serving size is also much smaller, which minimizes any potential risk even more.  

 

Aluminum in foods is not a cause for concern for toxicology experts because orally consumed aluminum is not considered to be very bioavailable from the gut, nor persistent in the body. Less than 1% is typically absorbed from our G.I. tracts, and virtually all of that has been shown to be excreted in the urine or feces. (Injectable sources, such as vaccine adjuvants, present a separate issue as absorption is not constrained by an effective gut barrier.)

 

Some companies tout lower levels of aluminum in their chlorella products as a marketing distinction, but admit that the levels being compared are far lower than in most common foods that are considered very healthy, i.e. cruciferous vegetables; despite the overwhelming safety data showing no real risk from consuming these foods that are normally considered to be good for us.

 

Here is a toxicology evaluation of dietary aluminum safety: https://www.ncbi.nlm.nih.gov/pubmed/11259180

Is Carrageenan Safe or Dangerous?

Undenatured carrageenan is a natural stabilizer, binding agent, and emulsifier used in products such as toothpaste in place of SLS and other truly undesirable ingredients commonly used in mass market products. It is also used in some vegan-friendly softgel capsule material as an alternative to animal-derived gelatin.

There is an Internet myth that carrageenan is unsafe; due primarily to confusion with a so-called “denatured carrageenan” polymer that is actually poligeenan, a heavily processed low molecular weight seaweed derivative currently used only as an x-ray imaging component. Poligeenan, previously used in pharmaceuticals, is quite different from the undenatured high molecular weight material that we use. Due to the safety concerns over poligeenan, regulations routinely require the carrageenan added to foods to have high molecular weight to ensure its integrity. But there are no unresolved safety concerns with undenatured carrageenan. 

Carrageenan has been thoroughly vetted by national and international public health authorities over a number of decades, even recently in response to the ongoing blogger-driven controversies, so there is no remaining basis of concern. Even its use in infant formulas was recently reconfirmed to be safe, and it’s helpful in distributing the nutrients more evenly to avoid the settling out that could otherwise cause uneven nutrient intake when a bottle is only partially consumed. 

After repeated investigations, the evidence for carrageenan safety is stronger than ever. Carrageenan is extremely safe and present in a number of healthy seaweeds; only the denatured form of carrageenan - a drug - is toxic. 

References:        

·        Public health and carrageenan regulation: a review and analysis. Borowitzka et al. (eds.), Nineteenth International Seaweed Symposium. DOI: 10.1007/978-1-4020-9619-8_8. Developments in Applied Phycology.

·         http://www.ncbi.nlm.nih.gov/pubmed/24467586

·         http://www.foodproductdesign.com/blogs/formulating-foods/2014/07/fao-who-carrageenan-safe-in-infant-formula.aspx

·         http://www.ncbi.nlm.nih.gov/pubmed/12389870

·         http://www.foodinsight.org/blogs/why-you-should-care-about-carrageenan

Does the Cyanocobalamin form of vitamin B-12 have toxic levels of cyanide?

All plants produce cyanide as a by-product of ethylene synthesis. Some plants naturally contain small amounts of cyanide compounds, including stone fruits (almonds, apples, cherries, peaches, and apricots) as well as lima beans, flax seeds, barley, sorghum, white clover, cassava (tapioca), and bamboo shoots.

The amount of cyanide (2% of the weight, or 20 micrograms cyanide in a 1 mg cyanocobalamin tab) is far less than ingested in many natural foods. Following absorption, vitamin B-12 from whatever source is transformed to either methylcobalamin or 5’-deoxyadenosylcobalamin (dibencoszide). Dibencozide is the predominant form of vitamin B-12 in human tissues (up to 70%).

The human body can detoxify a small amount of cyanide in the liver through the thiosulfate (sulfation) pathway. Poisoning occurs when there is not enough thiosulfate to neutralize all the cyanide present. When you’re talking about a dangerous dose of cyanide, it generally means between 50 and 200 milligrams of hydrogen cyanide… but a 1000 microgram (1 mg) pill of the vitamin B-12 supplement cyanocobalamin contains only 20 micrograms of cyanide, and according to dietitian Jack Norris, “the amount of cyanide in cyanocobalamin is considered to be physiologically insignificant.” That’s 20 micrograms, versus milligrams. There are 1000 micrograms in a milligram, which puts the amount of cyanide in a typical B12 supplement far below toxic levels. http://eatdrinkbetter.com/2012/02/22/cyanide/

Neither the U.S. National Institutes of Health’s Institute of Medicine (IOM) nor the European Food Safety Agency (EFSA) have set a Tolerable Upper Intake (UL) level of Vitamin B-12 since each agency has concluded that it is not possible to derive an Upper Level because no clearly defined adverse effect could be identified from medical reports.

• The IOM reported, “The IOM did not establish a UL for vitamin B-12 because of its low potential for toxicity. In Dietary Reference Intakes: Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline, the IOM states that "no adverse effects have been associated with excess vitamin B-12 intake from food and supplements in healthy individuals". Findings from intervention trials support these conclusions.”
• The EFSA reported, “There are also no adverse effects known for vitamin B12 from foods, or from supplements in amounts far in excess of needs.”

Therefore, cyanocobalamin, the predominate form of supplemental vitamin B-12, has been deemed non-toxic even at high levels of intake and the presence of small amounts of cyanide is not unusual in foods.

Sources:
• Centers for Disease Control and Prevention
• Canadian Food Inspection Agency
• Phys.org
• NIH IOM http://ods.od.nih.gov/factsheets/VitaminB12-HealthProfessional/
• EFSA http://www.slv.se/upload/dokument/efsa/upper_level_opinions_full-part33,0.pdf

Myths about stearate "risks"

There are some common myths about stearates. Please allow me to describe the stearates that are utilized in making nutritional supplements, and how they are used, and other pertinent information on their safety and use in dietary supplements and foods.

Stearic acid is converted into oleic acid in vivo, so becomes a similar fat as is found in olive oil. In fact, one jumbo olive is estimated to contain 13 milligrams (.013 g) of stearic acid (C 18:0), many times more than is used in any pills or capsules. http://www.oliveoilsource.com/olivechemistry.htm

“Stearic acid is well absorbed by the gut and is transported in chylomicrons and remnant particles before being picked up by the liver. Once there, an interesting paradox occurs in that excess stearic acid is simply converted to the 18-carbon monounsaturated oleic acid via a desaturase enzyme in the liver (3) and then recirculates in lipoprotein complexes as oleic acid, which is not hypercholesterolemic. Thus, conversion to oleic acid may explain why stearic acid does not elevate plasma cholesterol concentrations.”

Supplement manufacturers rarely use more than 2% and usually far less or none at all, even though common foods contain much more (beef fat is 19% stearates; cocoa butter is 30%) and stearates are Generally Recognized As Safe (GRAS). It is unusual that they would use more than1-2% in a product, and when they do use them it is typically used in microgram amounts to help process only sticky or non-flowing materials.

The hydrogenation process is not used for the stearic acid in the magnesium stearate. It is possible to convert oleic acid to stearic acid by hydrogenation, but that is not necessary (or desirable) with sources that are already high in stearic acid and low in oleic acid. Lipase-catalyzed interesterification is a viable alternative to hydrogenation these days, for example, if one were to want to convert oleic acid to stearic acid.

No consumer should be inhaling stearates, so the issue of being hazardous is also a bogus one that should be relegated to producers and manufacturers. You can actually say far worse about the hazards of inhaled enzymes, for example. Most supplement materials have MSDS handling sheets that mention the dangers of inhalation. There are no known significant dangers from normal oral consumption or skin contact.

The reason dietary stearic acid is considered benign is based on its failure to elevate plasma cholesterol concentrations (1, 2). Foods naturally rich in stearic acid and other saturated fats include: Red meat (beef, pork, or lamb) High-fat dairy products (whole milk, cheese, butter, and ice cream) Chocolate, Lard, Coconut oil.

For more on stearates, please see: http://www.nowfoods.com/index.php?action=itemdetail&item_id=93528.

Also, the accompanying chart has the percentages of stearic acid in common foods (4). As you can see, stearic acid is far more abundant in olive oil, butter and lard than in dietary supplements as a percentage, with grams in foods and micrograms (possible low milligram levels) in only certain dietary supplements:

A common reference is to a 1990 study in the journal Immunology, but the reference is hardly satisfactory as a demonstration of the alleged harm of stearic acid. This was a test tube study that has not been replicated in living beings, with an artificial situation providing high concentrations of stearic acid exposed to isolated immune cells for hours at a time. It was actually done as a way to investigate whether prolonged high dose stearic acid administration could possibly be used to suppress the immune system for an autoimmune disease treatment. (5) It was definitely NOT a demonstration that this would work the same way with dietary supplements or with foods containing stearic acid. The effect was dose- and time- dependent; with a sustained, prolonged exposure over an 8-hour period that is impossible to replicate in the living human body. For a test tube study, it would first have to be shown that the mechanism was valid in vivo before it could be considered reasonable to extrapolate it to actual living organsms. This study did not do that; nor has any other, to date.

In conclusion, since this mechanism has not been proven in humans or had additional verifying studies, since humans have much more complex metabolic activities, since stearic acid is easily absorbed from the gut and then readily converted to oleic acid in the liver (in vivo), since manufacturers use far less than this study gave and with only a brief exposure, and since people get stearic acid in many common oil-containing foods in far greater amounts than are used in dietary supplements, I conclude that the fears about the use of stearates in dietary supplements are unproven and speculative at best, slanderous and unscientific at worst.

For a second opinion, please see the website of Ray Sahelian, M.D. at http://www.raysahelian.com/magnesiumstearate.html

REFERENCES
1. Yu S, Derr J, Etherton TD, Kris-Etherton PM. Plasma cholesterolpredictive equations demonstrate that stearic acid is neutral and monounsaturated fatty acids are hypocholesterolemic. Am J Clin Nutr 1995;61:1129–39.
2. Aro A, Jauhiainen M, Partanen R, Salminen I, Mutanen M. Stearic acid, trans fatty acids, and dairy fat: effects on serum and lipoprotein lipids, apolipoproteins, lipoprotein(a), and lipid transfer proteins in healthy subjects. Am J Clin Nutr 1997;65:1419–26.
3. Lin DS, Connor WE, Spenler CW. Are dietary saturated, monounsaturated, and polyunsaturated fatty acids deposited to the same extent in adipose tissue of rabbits? Am J Clin Nutr 1993;58:174–9.
4. http://www.nebeef.org/post/lfu/Stearic_Acid.pdf
5. Tebby PW, Buttke TM. Molecular Basis for the Immunosuppresive Action of stearic acid on T Cells. Immunology. 1990;70:379-384.