Vitamin B12 - A Nutrition Guide for Vegetarians & Vegans: From Nori to Mushrooms, Omnivores Can Benefit, Too!

With 77µg per 100g of the Nori leaves in the wrapping sushi makes an excellent B12 source, even if you stick to the vegan, no tuna version ;-)

If this is not your first visit to the SuppVersity you will be aware that I am not a exactly a proponent of vegetarianism let alone vegan dieting. Just like any other severely restrictive diet people who don't eat animal products are at an increased risk of nutrient deficiencies.

For vegetarians and even more so for vegans, it is not exactly easy to cover their daily requirements of vitamin A, vitamin D3, iron, cholesterol (yes, cholesterol is an essential nutrient!), n-3 polyunsaturated fatty acids and saturated fats. The most urgently needed nutrient for the average vegetarian / vegan dieter, however is vitamin B12, or cobalamin, as scientists say.

Actually dairy happens to be an excellent B12 source. Why not become lacto-vegetarian?

Dairy Has Branched-Chain Fatty Acids!

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Is There a "Fat Advantage" for Dairy Lovers

Want B12, But Hate Meat? Drink Milk!

Vitamin B12 is a water-soluble vitamin with a key role in the normal functioning of the brain and nervous system, and for the formation of blood. It is one of the eight B vitamins. It is normally involved in the metabolism of every cell of the human body, especially affecting DNA synthesis and regulation, but also fatty acid metabolism and amino acid metabolism. Neither fungi, plants, nor animals - including humans - are capable of producing vitamin B12. Therefore a sufficient intake of vitamin B12 is essential for optimal health.

Even in omnivorous humans, vitamin B12 deficiencies are frequent (Stabler. 2004). Among vegetarians and specifically vegans, it is yet rampant (Pawlak. 2013; Pawlak. 2014).

Figure 1: Reliable data on B12 levels is scarce. Based on surrogate markers and B12 deficiency symptoms scientists are still certain that "B12 deficiency as a worldwide problem." (Stabler. 2004) - one vegetarians are particularly susceptible to.

In the latest review by Pawlak et al. who included only studies that assessed serum vitamin B12 an reported actual percentages of vitamin B12 deficiency (40 studies total)...

• the deficiency prevalence among infants reaches 45%,
• the deficiency among the children and adolescents ranged from 0 to 33.3%, and 
• the deficiency among pregnant women ranges from 17 to 39%, dependent on the trimester

Adults and elderly individuals who follow a vegetarian lifestyle had a deficiency range from 0–86.5%. In general, higher deficiency prevalence was reported in vegans than in other vegetarians.  Accordingly, Pawlak et al. conclude that...

"[...]with few exceptions, the reviewed studies documented relatively high deficiency prevalence among vegetarians. Vegans who do not ingest vitamin B12 supplements were found to be at especially high risk." (Pawlak. 2014)

For vegans, specifically, the scientists recommend the routine use of vitamin B12 supplements to ensure adequate vitamin B12 intake and point out that "[v]egetarians, regardless of the type of vegetarian diet they adhere to, should be screened for vitamin B12 deficiency." (Pawlak. 2014)

Why is it so difficult for vegetarians and vegans to meet their requirements?

The Institute of Medicine’s recommended dietary allowance (RDA) of B12 needed to meet an adult’s requirement as 2.4mg per day. B12 is synthesized only by microorganisms, and this is why natural food sources of B12 are limited to meats and foods of animal origin.

 "Clams and beef liver are the highest sources of B12, containing about 84 and 71mg of B12 in a 3 oz serving (USDA. 2011). The amount of B12 found in a chicken varies from about 3.3mg in the entire chicken liver to 0.03mg in achicken’s neck. Pork contains between 0.3mg of B12 in each sausage patty to about 11.4mg in pork liver. 6 The content of B12 in fish ranges from about 9mg in one half of a fillet of sockeye salmon to about 0.5mg in a 3 oz serving of yellow fin tuna." (Pawlak. 2013)

Needless to say that a vegetarian or vegan person mustn't eat any of the aforementioned "good" B12 sources. The question is thus: Where can a vegan or vegetarian get his B12 from?

Diagnosis of low B12 levels is tricky! The most commonly used cobalamin essay has a sensitivity of "only" 62.6% and produces 22%+ false positives. An often-used alternative, the holotranscobalamin essay is a tad better, but with a sensitivity of 64.7% and 18.4% false positives, not exactly accurate, either (Carmel. 2013). Until now no 100% reliable test is available and studies like Salomon (2005) show that patients with "normal" plasma cobalamin levels, but symptoms vitamin B12 deficiency improve after treatment with the vitamin.

In view of the fact that the name of this website contains the word "supplement", the most obvious and probably safest source are supplements. In that, it's important to point out that not all supplements that promise to solve the vegetarian B12 problems will actually deliver.

Fourteen years ago, Micheal S. Donson tested the efficacy of sublingual cobalamine tablets, nutritional yeast, and probiotic supplements in a group of Hallelujah dieters and other raw-food vegetarians and found that only the former two, i.e. the sublingual cobalamine tablets and the nutritional yeast that contained 5µg of cyanocobalamin per tablespoon brought his subjects' depleted B12 levels back into the normal range. The probiotic supplement, on the other hand, was useless (Donaldson. 2000).

For patients with insufficient intrinsic factor production oral supplements are not suitable, though. For them, only injectable vitamin B12 will reliably bring their levels back up (Katz. 1972). People with low stomach acid, which often occurs with aging, as well, and people with gastric bypass (Smith. 1993) have similar, but less pronounced problems to cover their B12 requirements from oral sources (dietary and supplemental).

Now, supplementation and injections are nice, but isn't is possible to get your B12 from foods without having to eat meat and animal products?

In general, it is possible, but there is one major problem: The total content and bioavailability of vitamin B12 in food sources vegetarians and vegans can eat is comparably low.

Table 1: Content and bioavailability of selected "good" dietary sources of vitamin B12 (Watanabe. 2007)

If you take a look at the data in Table 1 you will see that the only source that can keep up with fish and meat are algae. Chloeralla in particular is an excellent source of dietary B12 for both vegetarians and, if I didn't miss yet another stupid dogma, vegans, as well (Watanabe. 2007).

In a previous study, Watanabe et al. (2002) have found that chlorella tablets, but not spirulina, which contains mostly pseudy vitamin B12 is a suitable source of vitamin B12 for man (and woman ;-).

In a more recent overview of vegetarian and vegan B12 sources, the researchers from the United Graduate School of Agricultural Sciences at the Tottori University in Japan (Watanabe. 2014) compiled a comprehensive overview of suitable B12 sources which includes...

• 

  Are "organic" vegetables worth it? Find out in a previous article.

  Vitamin B12-Enriched Beans and Vegetables Produced Using Organic Fertilizers or Hydroponics -- Previous research has shown that you can significantly increase the B12 content of spinach by adding an organic fertilizer such as cow manure. Practically speaking this is an increase to to approximately 0.14 μg/100 g fresh weight - that's huge considering the fact that "regular" spinach contains < 0.01µg/100g vitamin B12.
  
  In view of the fact that the RDA for B12 is 2.4 μg/day that's still too little to be able to cover your B12 needs from spinach alone. Still, in the future we may be seeing other "high B12" vegetables on the market even non-vegetarian dieters may benefit from.
• Fermented Beans and Vegetables -- The Vitamin B12 content of soybeans is low or undetectable. In the course of the fermentation process soybean products are yet loaded with B12, so that fermented soybeans (Tempe, a traditional Indonesian food that's made of fermented soybeans) can contain up to 8.0 μg B12 per 100g (Nout. 1990)
  
  Comparable increases in B12 content have been observed in vegetables that have been fermented with certain lactic acid or propionic bacteria (up to 10µg/100g; Gupta. 1998).
  
  

  

  "Pesticide pollution: Chinese tea may not be safe to drink," this is what you could read on the website of Greenpeace in 2012, already and obviously this has not changed over the last 2 years | read more

  Tea, of which most people forget that it is fermented (not green tea, though), as well can also contain significant amounts of vitamin B12. For black tea (Batabata-cha), scientists have shown that drinking 50 mL/day, equivalent to a daily dose of 1 ng Vitamin B12, for 6 weeks, compensated the B12 deficiency of B12 deficient rodents (Kittaka-Katsura. 2004). As Watanabe et al. point out, results like these "indicate that Vitamin B12 found in fermented black tea is bioavailable in rats." Unfortunately, the same cannot be said for human beings, where the consumption of 1–2 L of the fermented tea drink, which is equivalent to 20–40 ng of Vitamin B12, is not sufficient to meet the RDA of 2.4 μg/day for adult humans.
• Edible Mushrooms --  Zero or trace levels (approximately 0.09 μg/100 g dry weight) of Vitamin B12 were measured in the dried fruiting bodies of porcini mushrooms (Boletussp.), parasol mushrooms (Macrolepiota procera), oyster mushrooms (Pleurotus ostreatus), and black morels (Morchella conica).
  
  

  

  Figure 2: The micronutrients in nori and dried shiitake mushrooms complement each other perfectly (see bottom line for explanation)

  In contrast, the fruiting bodies of black trumpet (Craterellus cornucopioides) and golden chanterelle (Cantharellus cibarius) contained higher levels of Vitamin B12 (1.09–2.65 μg/100 g dry weight) than the above mentioned mushrooms (Watanabe. 2012).
  
  In addition, high levels of Vitamin B12 were detected in the commercially available dried shiitake mushroom fruiting bodies (Lentinula edodes), which are used in various vegetarian dishes. The Vitamin B12 contents of dried shiitake mushroom fruiting bodies (100 g dry weight) significantly varied and the average Vitamin B12 value is approximately 5.61 μg (Bito. 2014). 

In conjunction with algae and algae supplements the aforementioned vegetarian sources of B12 may in fact be sufficient to cover the daily requirements of 2.4µg of vitamin B12.

Milk has a built-in B12 absorption enhancer (learn more). Now you tell me: Who would ever doubt that nature knows best?

Bottom line: Of all vegetarian B12 sources, nori is the one marine source of vitamin B12, Watanabe et al. highlight in particular. The consumption of only 4g of dried purple laver (Vitamin B12 content: 77.6 μg /100 g dry weight) supplies the RDA of 2.4 μg/day. Moreover, nori can be easily consumed as a wrapping for rice and fillings and retains most of its precious B12 content upon heating (Miyamoto. 2009).

In conjunction with dried shiitake mushroom fruiting bodies that contain 18.9 mg of Vitamin D2 (ergocalciferol) and 2.0 mg of iron, both likewise micronturients vegetarians usually don't get enough of in their diets, the dried purple lavers that are rich sources of n-3 polysaturated fatty acids and can be easily integrated in Italian, French, and other forms of Western cuisine, are thus probably the best non-supplemental source of B12 vegetarians can get | Comment on Facebook!

References:

• Bito, Tomohiro, et al. "Characterization of vitamin B< sub> 12</sub> compounds in the fruiting bodies of shiitake mushroom (< i> Lentinula edodes</i>) and bed logs after fruiting of the mushroom." Mycoscience (2014). 
• Carmel, Ralph. "Diagnosis and management of clinical and subclinical cobalamin deficiencies: Why controversies persist in the age of sensitive metabolic testing." Biochimie 95.5 (2013): 1047-1055.
• Gupta, Uma, E. R. Rati, and R. Joseph. "Nutritional quality of lactic fermented bitter gourd and fenugreek leaves." International journal of food sciences and nutrition 49.2 (1998): 101-108. 
• Katz, Max, Sook K. Lee, and Bernard A. Cooper. "Vitamin B12 malabsorption due to a biologically inert intrinsic factor." New England Journal of Medicine 287.9 (1972): 425-429.
• Kittaka-Katsura, Hiromi, et al. "Characterization of corrinoid compounds from a Japanese black tea (Batabata-cha) fermented by bacteria." Journal of agricultural and food chemistry 52.4 (2004): 909-911.
• Miyamoto, Emi, et al. "Characterization of vitamin B12 compounds from Korean purple laver (Porphyra sp.) products." Journal of agricultural and food chemistry 57.7 (2009): 2793-2796.
• Nout, M. J. R., and F. M. Rombouts. "Recent developments in tempe research." Journal of Applied Bacteriology 69.5 (1990): 609-633.
• Pawlak, Roman, et al. "How prevalent is vitamin B12 deficiency among vegetarians?." Nutrition reviews 71.2 (2013): 110-117.
• Pawlak, R., S. E. Lester, and T. Babatunde. "The prevalence of cobalamin deficiency among vegetarians assessed by serum vitamin B12: a review of literature." European journal of clinical nutrition 68.5 (2014): 541-548. 
• Smith, C. Daniel, et al. "Gastric acid secretion and vitamin B12 absorption after vertical Roux-en-Y gastric bypass for morbid obesity." Annals of surgery 218.1 (1993): 91.
• Solomon, Lawrence R. "Cobalamin-responsive disorders in the ambulatory care setting: unreliability of cobalamin, methylmalonic acid, and homocysteine testing." Blood 105.3 (2005): 978-985.
• Stabler, Sally P., and Robert H. Allen. "Vitamin B12 deficiency as a worldwide problem." Annu. Rev. Nutr. 24 (2004): 299-326.
• USDA National Nutrient Database for Standard Reference, Release 18.Vitamin B12 (mg) Content of Selected Foods Per Common Vitamin B-12 Measure, Sorted by Nutrient Content. 2005; Available at: http://www.nal.usda.gov/fnic/foodcomp/Data/SR18/nutrlist/sr18w418.pdf. Accessed 27 November 2011. 
• Watanabe, Fumio, et al. "Characterization and bioavailability of vitamin B12-compounds from edible algae." Journal of nutritional science and vitaminology 48.5 (2002): 325-331.
• Watanabe, Fumio. "Vitamin B12 sources and bioavailability." Experimental Biology and Medicine 232.10 (2007): 1266-1274.
• Watanabe, Fumio, et al. "Characterization of vitamin B 12 compounds in the wild edible mushrooms black trumpet (Craterellus cornucopioides) and golden chanterelle (Cantharellus cibarius)." Journal of nutritional science and vitaminology 58.6 (2012): 438-441.
• Watanabe, Fumio, et al. "Vitamin B12-Containing Plant Food Sources for Vegetarians." Nutrients 6.5 (2014): 1861-1873.

Want B12, But Hate Meat? Drink Milk! SNAC-Fortified Cyanocobalamin 136% More Bioavailable Than Standard B12 - Still Less Effective Than B12 From Cow's Milk

Figure 1: Milk still rules the
world (of B12 supplements ;-)

Vitamin B12 deficiency is probably more prevalent, than many people would have it. The water-soluble vitamin is most abundant in foods of animal origin and vegetarians (let alone vegans) are as much at risk of having inadequate B12 levels, as people with achlorhydria and, consequently, low intrinsic factor (an enzyme that requires an acidic environment to function and facilitate the utilization of B12 from foodstuff), or more generalized disturbances of the gastrointestinal structure due to aging (food-cobalamin malabsorption becomes increasingly prevalent after the age of 50), gastric resection, ileal resection, Crohn's disease, and bacterial overgrowth of the intestine. With vitamin B12 deficiency affecting cell division and precipitating to megaloblastic anaemia and neuropathy, close monitoring not only of vitamin B12 intake, but also of its proper utilization is of utmost importance for people belonging to one of the aforementioned groups.

Scientists from Emisphere Technologies in Cedar Knolls, New Jersey, have now come up with a new cyanocobalamin/SNAC coformulation, in which the sodium caprylic acid salt, N-[8-(2-hydroxybenzoyl)amino]caprylate (SNAC), a proven drug delivery agent, shall facilitate a more pronounced and more reliable absorption of orally supplemented vitamin B12 (Castelli. 2011). The formula, which contained 5-mg cyanocobalamin and 100-mg SNAC was administered to 6 human subjects in the fasted state in the form of 1 tablet, which had to be taken with 50 mL of water. Blood samples were taken at staggered intervals with the last blood draw taking place 24h after the ingestion of the B12/SNAC coformulation.

Figure 1: Time to and maximal serum concentration of B12 after oral administration or infusion of cyanocobalamine with and without SNAC; note: in order to compensate for the major differences between oral cyonocobalamine with and without SNAC a logarithmic scale was used (data adapted from Castelli. 2011).

As expected the concomitant administration of sodium N-[8-(2-hydroxybenzoyl)amino]caprylate (SNAC) increased the meager biovalability of cyanocobalamine (which is absorbed really poorly, anyway) significantly:

Absolute bioavailability of B12 with the SNAC formulation was calculated from non–baseline-adjusted data to be 5.09% and was significantly greater (P < 0.05) than the commercial formulation (2.16%).

In view of the recently elucidated bioavailability of natural B12 from plain cow's milk (Matte. 2011), or should I say "liquid white gold", the 136% increase in bioavailability Christina Castelli and her coworkers achieved with their artificial combination of B12+SNAC appear quite ludicrous. 8%-10% that is the bioavailability et al. report in Jacques Matte and his colleagues from Canada report in their study on the bioavailability of vitamin B12 from cow's milk. Granted, this is a pig model, but other than rodents, which are usually used when it comes to studies, in which surgical interventions are necessary to elucidate the exact pharmacodynamics of a specific drug, pigs provide a very adequate model for the human gastrointestinal system, or as Miller and Ullrey already stated it in a 1987 paper on the "The Pig as an Animal Model For Human Nutrition" (Miller. 1987)

[...]with the possible exception of nonhuman primates, it is apparent that the omnivorous pig is one of the best models for study of nutrition issues in the omnivorous human.

This long established adequacy of the pig model of the human gastrointestinal tract has only recently been confirmed by Goulloteau et al. (Guilloteau. 2010). Matte et al.'s result that vitamin B12, which is naturally and abundantly present in cows’ milk, is more available at the intestinal level than the synthetic form - even if the latter is supplemented with SNAC - are thus very likely to apply to humans, as well.

Figure 2: Pharmacokinetics of vitamin B12 from different sources measured in pigs with an ultrasonic flow probe around the portal vein and a catheter inside the portal vein; values expressed as differences vs. unsupplemented animals; both values for cyanocobalamine alone are effectively 0, i.e not different from unsupplemented pigs (data adapted from Matte. 2011).

These results are also in accordance with retrospective studies in human subjects showing that vitamin B12 status is highly correlated with dairy product intake and studies on the absorption (absorption = entering the cells vs. bioavailability = becoming available in the blood stream) of vitamin B12 from dairy products in older men and women (>60y) by Robert M. Russel et al. (Russel. 2001), who report absorption of up to 65% for milk, which would be almost identical to the generally accepted absorption coefficient for meat products.

Note: Using a pig model Matte et al. were able to actually measure the portal-drained viscera (PDV) flux of vitamin B12, which provides more reliable results than radio-labelling studies, as they were used in Russel et al. It is thus all the more intriguing that the PDV for the unsupplemented diet or cyanocobalamin supplements [...] were not different from 0", or in other words - providing pigs with cyanocobalamine, which is the form of vitamin B12 that is used in most common dietary supplements, had no effect  on serum B12 concentrations, at all.

So, what does this tell you, after all? Well, let me phase it like that: If you have a Ferrari Enzo (milk and meat) waiting for you at the front door (in the fridge), wouldn't it be plain-out stupid to try to chip-tune (add SNAC) the family car (cyanocobalamine)? An the moral of the Story? Eat, don't supplement your vitamins!

Biotin, Folic Acid & B12 & Glucose Management | Part IX of the "There is More To Glucose Control Than Low Carb" - Series: Are Extra "B"s Good for Non-Diabetics as Well?

There is evidence for beneficial effects of B7 and B12 in Alzheimer's. Yet although the this disease is often called "diabetes of the brain" the evidence that B7 and B12 would do anything but ameliorate the damage due to increased blood glucose levels and decreases insulin sensitivity is non-existent.

I guess, you will remember that my analysis of the role of thiamin (B1), riboflavin (B2), pantothenic acid (B5) and pyridoxin (B6) revealed... well, what did it reveal? Not much, aside from the fact that the importance of these B-vitamins in glucose management is probably overrated. For niacin, the fifth B-vitamin I have covered in this series, thing looked much different: At high doses niacin (as nicotinic acid) will have profound effects on your glucose metablism and whether those are beneficial or bad for you may eventually depend on the timing of your niacin supplements.

In today's installment of the "There is More to Glucose Control Than Low Carb"-Series, we will tackle the rest of the B-vitamin pack to find out whether we have to add biotin (B7), folic acid (B9) and cobalamin (B12) to our list of "non-carbohydrate nutrients" with profound effects on blood glucose management.

You can learn more about this topic at the SuppVersity

Proteins, Peptides & Blood Glucose

SFA, MUFA, PUFA & Blood Glucose

Vitamin D & Diabetes

Glucose Manager Calcium?

Flush & No-Flush Niacin & Diabesity

Vitamin C & Glucose Control

In view of the fact that B12 is one of the shining stars on the supplement firmament and its role in mitochondrial health, it appears to be logical to assume that a couple of additional cobolamine pills (or even injections) will also help you maintain / improve your insulin sensitivity. If we take a look at one of the standard lists of symptoms that occur with low B12 levels, we will yet find

"Pernicious anemia (numbness and tingling in hands and feet / nerve damage), shortness of breath, severe fatigue, birth defects, dementia, confusion, poor memory, depression, reduced WBCs and platelet formation, loss of appetite, weight loss, sore tongue, headaches, and nausea,"

but not a single hint that low vitamin B12 levels could compromise your blood glucose management. And still, even if there is no direct link between vitamin B12 and diabetes, there is more than one good reason for diabetics to take cobalamine supplements:

• 

  Glucose management is not among the standard functions of B7 and B12.

  improvements in diabetic neuropathy (Yaqub. 1992; Sun. 2005)
• increased risk of gestational diabetes with low B12 levels (Krishnaveni. 2009)
• epigenetic programing that increases type II diabetes risk in the offspring of B12 deficient mouse and man (Yajnik. 2008; Deshmukh. 2013) 
• diabetes induced cobalamine depletion (Solomon. 2011)
• the central role of B12 in the methylaction cycle and its role in glucose management (Finer. 2013)

On the other hand, many of the results of previous studies are of questionable value in view of the fact that serum vitamin B12 do not adequately reflecting vitamin B12 status in patients with type 2 diabetes (Obeid. 2013). It is thus no wonder that peer-reviewed evidence that would confirm any beneficial effects of B12 supplementation on glucose management is absent.

B12 injections & L-5-MTHF supplements? For both, folic acid and methylcobalamine the provision of adequate intake levels is essential for overall health. And with both you will find people who have a hard time meeting their biological requirement due to digestive (B12; esp. elderly individuals) and genetic defects (no conversion of folic acid to fale). For these people, but not for Mr. and Mrs. Average Joe it may thus be worth spending the extra bucks on hydroxcobalamine injections and L-5-Methyltetrahydrofolate (L-5-MTHF) supplements, even if they won't have immediate beneficial effects on their blood glucose management.

The same lack of conclusive evidence for it's direct contribution to / beneficial effects on glucose control can be found for folic acid, as well. Just like B12 it appears to help to buffer the neurological side effects of insulin resistance and reduce increased homocysteine levels of which some, but not all scientists believe that they would increase your risk of heart disease.
 
If it were not for biotin which has a whole host of peer-reviewed studies to support its ability to improve the insulin sensitivity of diabetic and pre-diabetic animals (Reddi. 1988) and human beings (McCarty, 1999).

Figure 1: Both blood lipids and glucose management of the diabetic subjects improved w/ chromium picolinate (600µg Cr) +biotin (2 mg) in study by Cesar Albarracin et al. (2008)

As it was the case in the study by Albarracin et al. Figure 1 is based on, biotin is often co-administered with chromium picolinate. As you can see with quite some success and the same increase in insulin release that will also occur in healthy individuals on high dose chromium supplements (learn more).

Beware: High dose biotin supplements are not necessarily good for healthy individuals!

And even though there is evidence that biotin will also have beneficial effects on glucose management, when it is administered (again in high doses of 1-2g) without chromium to patients with diet-induced insulin resistance & diabetes (Koutsikos. 1996; Zhang. 1996) and patients with type I diabetes (Hemmati. 2013), I have to warn you: If you don't have blood glucose issues to begin with, taking several grams of biotin per day could do more harm than good.

Figure 2: Changes in glucose (fasting glucose and insulin levels) and lipid management triglyceride and total cholesterol) after 4 weeks on 3x5mg/day biotine in healthy and diabetic individuals (Báez-Saldaña. 2004)

In the study that generated the data in Figure 2 (Báez-Saldaña. 2004), biotin failed to produce any (not even insignificant) improvements in glucose management in the diabetic subjects and led to allegedly non-significant increases in blood glucose and insulin levels in the healthy study participants (see Figure 2). With 3x5mg/day the dosage was yet exorbitantly high. It's thus not surprising that the effects were similarly detrimental as those of the high dose chromium regimen by the means of which Masharani et al. messed with the insulin sensitivity of their likewise healthy subjects a previously discussed study from 2012 (read more).

Biotin, rather for blood lipid than blood glucose management: Rather than for blood glucose, you may want to use biotin supplements for blood lipid management. As Asdrúbal Aguilera-Méndez and Cristina Fernández-Mejía argue in a 2012 paper in the scientific journal BioFactors, biotin works by increasing c-AMP and AMPK - both well, known mechanism that are triggered by lipid-lowering herbs and meds, as well. Larrieta et al. even argue that pharmacological doses of biotin will reduce the expression of lipogenic genes - genes which control, among other things, the conversion of glucose to triglycerides and the storage of the latter in the adipose organ. In a way, this mechanism could also be responsible for the increase in serum glucose Báez-Saldaña et al. observed in their high dose biotin supplementation study.

Well, the beneficial effects on blood lipids have been observed by  Marshall et al., as well (Marshall. 1979) - at only 0.9mg/day. In their study of the "effects of biotin on lipids and other constituents of plasma of healthy men and women", they observed (a) a significant negative correlation between plasma and biotin levels and (b) a reduction in plasma lipids in response to biotin supplementation that depended not on the dosing, but on the baseline levels, meaning that volunteers who initially had elevated levels of lipids showed greater lipid reductions than those who had normal levels of lipids.

Similar benefits occur at 1x5mg as they were administered by Revilla-Monsalve et al. to 18 diabetic and 15 normo-glycemic individuals. In contrast to the 3x5mg overdose in the previously cited study, though, the "[b]iotin treatment had no significant effects on cholesterol, glucose and insulin in either the diabetic or nondiabetic subjects." (Revilla-Monsalve. 2006).

So how much do you take? If you are asking me, the answer would be none, and that despite the fact that over here in Germany "food" is not as intoxicated... ah, I mean "fortified" with additional folic acid.

If you insist on supplementing stick to 400mcg (600mcg, when pregnant) of folic acid and max 500mg of methylcobolamine (highly orally bioavailable form of B12) per day. That's plenty.

And biotin? Well <500mcg per day probably won't hurt you.

So what? All useless? In the end, "useless" is probably a bit too strong of a word. There is no doubt that folic acid and B12 supplements won't be able to reverse diabetes, but they can ameliorate the side effects and are essential for women who want to make sure they don't pass your own pre-diabetes on to your offspring.

Biotin on the other hand, appears to have a place in the treatment of acute diabetes. For the average insulin sensitive SuppVersity reader who does not have elevated triglyceride levels or other blood lipid issue, high amounts of supplemental biotin (anything beyond 1mg per day chronically and 5mg per day in the short run) could even have similarly detrimental health effects as their comrades in crime, the highly popular chromium picolinate supplements.

References:

• Albarracin, Cesar A., et al. "Chromium picolinate and biotin combination improves glucose metabolism in treated, uncontrolled overweight to obese patients with type 2 diabetes." Diabetes/metabolism research and reviews 24.1 (2008): 41-51.
• Báez-Saldaña, Armida, et al. "Effects of biotin on pyruvate carboxylase, acetyl-CoA carboxylase, propionyl-CoA carboxylase, and markers for glucose and lipid homeostasis in type 2 diabetic patients and nondiabetic subjects." The American journal of clinical nutrition 79.2 (2004): 238-243.
• Deshmukh, Urmila, Prachi Katre, and Chittaranjan S. Yajnik. "Influence of maternal vitamin B12 and folate on growth and insulin resistance in the offspring." (2013): 145-156.
• Finer, S., et al. "The role of the one‐carbon cycle in the developmental origins of Type 2 diabetes and obesity." Diabetic Medicine (2013).
• Hemmati, Mitra, Homa Babaei, and Mohammadreza Abdolsalehei. "Survey of the Effect of Biotin on Glycemic Control and Plasma Lipid Concentrations in Type 1 Diabetic Patients in Kermanshah in Iran (2008-2009)." Oman medical journal 28.3 (2013): 195.
• Koutsikos, Dimitris, et al. "Oral glucose tolerance test after high-dose iv biotin administration in normoglucemic hemodialysis patients." Renal failure 18.1 (1996): 131-137.
• Krishnaveni, G. V., et al. "Low plasma vitamin B12 in pregnancy is associated with gestational ‘diabesity’and later diabetes." Diabetologia 52.11 (2009): 2350-2358. 
• Larrieta, Elena, et al. "Pharmacological concentrations of biotin reduce serum triglycerides and the expression of lipogenic genes." European journal of pharmacology 644.1 (2010): 263-268.
• Marshall, M. W., et al. "Effects of biotin on lipids and other constituents of plasma of healthy men and women." Artery 7.4 (1979): 330-351.
• Masharani U, Gjerde C, McCoy S, Maddux BA, Hessler D, Goldfine ID, Youngren JF. Chromium supplementation in non-obese non-diabetic subjects is associated with a decline in insulin sensitivity. BMC Endocr Disord. 2012 Nov 30;12(1):31. 
• McCarty, M. F. "High-dose biotin, an inducer of glucokinase expression, may synergize with chromium picolinate to enable a definitive nutritional therapy for type II diabetes." Medical hypotheses 52.5 (1999): 401-406.
• Obeid, Rima, et al. "Serum vitamin B12 not reflecting vitamin B12 status in patients with type 2 diabetes." Biochimie 95.5 (2013): 1056-1061.
• Reddi, Alluru, et al. "Biotin supplementation improves glucose and insulin tolerances in genetically diabetic KK mice." Life sciences 42.13 (1988): 1323-1330.
• Revilla-Monsalve, Cristina, et al. "Biotin supplementation reduces plasma triacylglycerol and VLDL in type 2 diabetic patients and in nondiabetic subjects with hypertriglyceridemia." Biomedicine & pharmacotherapy 60.4 (2006): 182-185.
• Solomon, Lawrence R. "Disorders of cobalamin (vitamin B12) metabolism: emerging concepts in pathophysiology, diagnosis and treatment." Blood reviews 21.3 (2007): 113-130.
• Sun et al. "Effectiveness of vitamin B12 on diabetic neuropathy: systematic review of clinical controlled trials."ACTA NEUROLOGICA TAIWANICA 14.2  (2005): 48-54.
• Yajnik, C. S., et al. "Vitamin B12 and folate concentrations during pregnancy and insulin resistance in the offspring: the Pune Maternal Nutrition Study." Diabetologia 51.1 (2008): 29-38.
• Yaqub, Basim A., Abdulaziz Siddique, and Riad Sulimani. "Effects of methylcobalamin on diabetic neuropathy." Clinical neurology and neurosurgery 94.2 (1992): 105-111. 
• Zhang, Hong, et al. "A high biotin diet improves the impaired glucose tolerance of long-term spontaneously hyperglycemic rats with non-insulin-dependent diabetes mellitus." Journal of nutritional science and vitaminology 42.6 (1996): 517-526.

Science Round-Up Seconds: "Tomatorade(R)" or Why Tomato Juice is the Better Intra- & Postworkout Beverage. Up to 90% B12 Deficiency in Vegetarians & Vegans. Aluminum in Your Testes? Not With Vitamin E & Zinc.

Can't find "Tomatorade(R)", at your local supplement store, yet (surprising, right ;-)? The guys over @ SimplyRecipes have an easy and tweakable recipe describing how you can make your own "Tomatorade" or however you want to call it (photo by SimplyRecipes).

If you listened live to yesterday's installment of the SuppVersity Science Round-Up on Super Human Radio, you will probably have noticed that due to the technical problems and my teacherly tendency to talk for hours, Carl Lanore and I did not cover all the topics (click here do download the podcast if you haven't already done so)... but hey, that leaves more stuff for today, doesn't it?

I guess I will best package the newsitems into three servings, starting out with the one I like best, namely my Tomatorade(R) aka plain tomato juice news... but before I do so, I must thank Maxim Okhrimenko who corrected the statement I made about vodka in Russian babies' tea or other beverages. Normal Russians don't this. I actually did not intend to make that sound like "common practice" - sorry if it got across like that.

My sincere apologies for promoting prejudices like that. From a science perspective you could even argue that the Brits came up with the idea. In the 1850s William Woodward "invented" a concoction of dill seed oil, sodium bicarbonate and alcohol, called it "gripe water" and sold it as a soothing remedy for gastrointestinal troubles (Agarwal. 2000).

Tomatorade(R) - Tomato Juice turns out to be the ideal periworkout carb drink

What's LDH and CPK? While the former stands for lactate dehydrogenase and the latter is identical to CK, which is creatine kinase, both are considered markers of muscular exertion (LDH) and damage (CK) due to exercise. Very high levels of LDH occur for example in hemolytic situations, i.e. at times your red blood cells disintergrate or after a major trauma to a muscle (incl. a myocardial infarction), the same is true for CK, for which most laboratories will analyses tissue specific isoforms with CK-MB being the one that's indicating muscle damage from the minor DOMS after a leg workout to full rhabdomyolysis.

I know many of you will probably be shuddering, right now. "Carbohydrate drinks? I don't care if it's Tomato- or Gatorade, I don't want any of them." Still, what would you say, if I told you that "Tomatorade(R)", which consists of nothing else but 100% tomato juice could not just replenish your muscle glycogen levels, but would also reduce and even normalize LDH and CPK levels? Allow you to regenerate faster, train more frequently and eventually increase your performance and muscle gains- specifically if you are into weight lifting or other anaerobic activities? I see, now, I got you interested.

According to a paper that is going to be published in the next issue of Food Chemistry and Toxicology, the administration of tomato juice instead of a commercial exercise beverage to 9 out of 15 anaerobically trained athletes (11 men, 4 women) with elevated LDH (>300mg/dl) and CPK(>210mg/dl) baseline levels (as the scientists have it a clearcut sign of "endothelial dysfunction through oxidative stress" (Tsitsimpikou . 2013)) returned the LHD ad CPK levels back into the normal range in the course of the two months study period.

Figure 1: Effects of two month on an isocaloric amount tomato juice (here jovially called "Tomatorade(R)" ;-) vs. the regular carbohydrate workout drink the subjects usually consumed during and after their workouts (Tsitsimpikou. 2013)

Moreover, the consumption of vitamin, mineral and polyphenol-laden superdrink, in place of the athletes regular carbohydrate drink (the scientists made sure that the energy content was identical) also reduced the highly health relevant markers of whole body inflammation, homocysteine and C-reactive protein (CRP; see figure 1) - whether the mainly lycopene induced reductions in homocystein is actually protecting against endothelial damage or not, is yet still (or I should say, again) a matter of scientific debate (cf. Xaplanteris. 2012).

Brief update:  Just got a question from Sofeen on facebook about simply eating tomatoes. Now, you would have to eat plenty of them to see the effect, but in essence it should work. Nevertheless, when I contemplated the question I came up with an even better alternative: Tomato paste! When Tomatorade(R) is the carb beverage, then the paste would be one of those fancy carb gels - a gel, by the way, which has a 2.5x higher bioavailability for lycopene than you would get from regular tomatoes (Gärtner. 1997).

Vitamin B12 defieciency is rampant among vegetarians and (even more) vegans

I have previously pointed out that unless you are at least lacto-ovo-vegetarian, which means that you eat dairy products and eggs, you are going to have a very hard time building and maintaining the physique of your dreams. As a recent meta-analysis and review study by Pawlak et al. suggests, not being the leanest and most muscular on stage should yet actually be your least concern.

Suggested Read: "Want B12 But Hate Meat? Drink Milk!" Even some of the more advanced supplements cannot compete.

According to the data the researchers from different US institutions collected, the deficiency rates for "normal" vegetarians are

• 62% among  pregnant  women,
• between  25% and almost 86% among children,
• 21–41% among adolescents, and
• 11–90% among the elderly

Even higher rates, bordering the 90%+ range, when they were measured by holo-transcobalamin II essays were reported for vegans (adults). On top of that the scientists did not find any confounding factors,:

"The main finding of this review is that vegetarians  develop  B12 depletion or deficiency  regardless  of demographic  characteristics,  place of residency,  age, or type of vegetarian  diet. Vegetarians should thus take preventive measures to ensure adequate intake of this vitamin, including regular consumption of supplements containing B12." (Pawlak. 2013)

As preferable dietary sources the researchers suggest, the aforementioned dairy products and eggs:

• milk, which contains between 0.3 and 0.4 mg/100 g of B12, with an absorption rate of about 65%.
  
• the B12 content of cheese or cottage cheese ranges from 20 to 60% that of milk.
• the amount of B12 in a whole egg is between 0.9 and 1.4 mg/100g

Unfortunately, the amount of B12 is profoundly reduced during the heating process. For milk the B12 loss amounts to up to 30-50%, when you boil it and I bet you won't be much better off with hard boiled (yolks = hard) eggs.

If you avoid meat not for ethical reasons, but because you are afraid it's bad for you, read the "Meat-Ology" post

The scientists also point out that the vegan myth that your body a great ability to store B12 and it would take years if not decades for them to be depleted:

"Studies do not support the position that it takes up to 20 or 30 years to develop a deficiency.7 According to Donaldson, 47% of the sample developed a deficiency, and most of these individuals had adhered to a raw vegan diet for between 23 and 49 months or about 2–4 years. In a study conducted by Herrmann et al.66% of German participants who had adhered to a vegetarian diet for at least 2 years were found to be B12 deficient." (Pawlak. 2013)

Since the whole problem is further increased by the lack of hydrochloric acid (low-to-no intrinsic factor production, which is necessary for the absorption of B12), low iron induced damage to the gut mucosa and subsequent nutrient malabsorptions, I'd suggest that all of you who insist on following a vegetarian life-style go, have their levels checked and get some B12 injections if you are where Pawlak et al. believe you are: Rock bottom.

Protect your testes, rescue your sperm and testosterone production

A recently published paper has taken yet another look at ways to prevent testicular damage / toxicity subsequent to heavy metal exposure. Other than usual, the "suspect" is yet not lead, but rather aluminum, which was administered in toxic doses to male albino rodents.

Figure 2: Relative levels of testosterone, FSH, LH and prolactin in aluminum (50mg/kg) treated male albino rats after the administration of zinc, vitamin E or both; data expressed relative to healthy (non-Al intoxicated) control (Rawy. 2013)

As the data in figure 2 goes to show you, the Saudi-Arabian researchers were able to counter much of the detrimental effects on testicular morphology, spermatogenesis and hormone production by administering either zinc sulfate or vitamin E alone or in conjunction at human equivalent doses of 8mg/kg zinc sulfate (I may remind you that these were 8mg/kg of zinc sulfate, not of elemental zinc, so that we are talking about ~1.8mg/kg elemental zinc) and 2.4mg/kg vitamin E (~1,200-1,500IU), respectively.

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Now while that's it as far as today's Seconds are concerned, tomorrow is Saturday and in case you are into those shorter news items, you better make sure to come back for another installment of On Short Notice. And just in case you have not done so already, I would also suggest that you take a peek at the following recent Facebook news:

Older tomato news: The dehydrotomatine, α-tomatineand trigonelline from green tomatoes has fat burning effects (read more).

• Galactooligosaccharides increase bifido bacteria content in obese patients and result in positive effects on the immune response, and insulin, total cholesterol and triglyceride concentrations (read more). 
• Women with brittle bones cannot squat? False! They must squat, recent study says (read more)
• The fries a mother eats during pregnancy predispose her kids to become obese and develop metabolic syndrome syndrome - at least if the oil was (as it almost always is) oxidized during the heating process (read more).
• The Zinc equation: For every doubling in Zn intake, the difference in Zn serum or plasma concentration is 6% - this assumes zinc intakes in the normal range of <30mg/day (read more).

As usually there will be more for you to read in the course of the next 24 hours - so just "like" the SuppVersity Facebook page to make sure you are not missing out on anything important ;-)

References

• Agarwal KN, Gupta A, Pushkarna R, Bhargava SK, Faridi MM, Prabhu MK. The gripe water story.J R Soc Med.2000;93:172-174.
• Gärtner C, Stahl W, Sies H. Lycopene is more bioavailable from tomato paste than from fresh tomatoes. Am J Clin Nutr. 1997 Jul;66(1):116-22.
• Pawlak R, Parrott SJ, Raj S, Cullum-Dugan, D Lucus, D. How prevalent is vitamin B12 deficiency among vegetarians? Nutrition Reviews. 2 JAN 2013 [epub ahead of print]
• Rawy SM, Seif Al Nassr FM. Zinc sulphate and vitamin E alleviate reproductive toxicity caused by aluminium sulphate in male albino rats. Toxicol Ind Health. 2013 Jan 2.
• Tsitsimpikou C, Kioukia-Fougia N, Tsarouhas K, Stamatopoulos P, Rentoukas E, Koudounakos A, Papalexis P, Liesivuori J, Jamurtas A. Administration of tomato juice ameliorates lactate dehydrogenase and creatinine kinase responses to anaerobic training. Food Chem Toxicol. 2013 Jan 3.
• Xaplanteris P, Vlachopoulos C, Pietri P, Terentes-Printzios D, Kardara D, Alexopoulos N, Aznaouridis K, Miliou A, Stefanadis C. Tomato paste supplementation improves endothelial dynamics and reduces plasma total oxidative status in healthy subjects. Nutr Res. 2012 May;32(5):390-4.