Sunday, April 20, 2014

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.
  • 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.