Biotin Abstracts 3

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Use of chromium picolinate and biotin in the management of type 2 diabetes: an economic analysis.
            (Fuhr et al., 2005) Download
This paper addresses the potential economic benefits of chromium picolinate plus biotin (Diachrome) use in people with Type 2 diabetes (T2DM). The economic model was developed to estimate the impact on health care systems' costs by improved HbA1C levels with chromium picolinate plus biotin (Diachrome). Lifetimes cost savings were estimated by adjusting a benchmark from the literature, using a price index to adjust for inflation. The cost of diabetes is highly dependent on the HbA1C level with higher initial levels and higher annual increments increasing the cost. Improvement in glycemic control has proven to be cost-effective in delaying the onset and progression of T2DM, reducing the risk for diabetes-associated complications and lowering utilization and cost of care. Chromium picolinate plus biotin (Diachrome) showed greater improvement of glycemic control in poorly controlled T2DM patients (HbA(1C) > or = 10%) compared to their better controlled counterparts (HbA(1C) < 10%). This improvement was additive to that achieved by oral hypoglycemic medications and correlates to calculated levels of cost savings. Average 3-year cost savings for chromium picolinate plus biotin (Diachrome) use could range from 1,636 dollars for a poorly controlled patient with diabetes without heart diseases or hypertension, to 5,435 dollars for a poorly controlled patient with diabetes, heart disease, and hypertension. Average 3-year cost savings was estimated to be between 3.9 billion dollars and 52.9 billion dollars for the 16.3 million existing patients with diabetes. Chromium picolinate plus biotin (Diachrome) use among the 1.17 million newly diagnosed patients with T2DM each year could deliver lifetime cost savings of 42 billion dollars, or 36,000 dollars per T2DM patient. Affordable, safe, and convenient, chromium picolinate plus biotin (Diachrome) could prove to be a cost-effective complement to existing pharmacological therapies for controlling T2DM.

Loss of taste responds to high-dose biotin treatment.
            (Greenway et al., 2011) Download
BACKGROUND AND OBJECTIVE:  We saw 2 patients who lost their sense of taste, which was restored by pharmacologic doses of biotin. The key objective is to describe the 2 case reports and suggest a potential treatment for unexplained loss of taste. METHODS AND DESIGN:  The first patient was a 67-year-old woman who lost her sense of taste taking Juvenon, a dietary herbal supplement containing acyl-L-carnitine, lipoic acid, calcium, phosphorus, and biotin 300 μg per day. The second patient was a 60-year-old man who lost his sense of taste after a sleeve gastrectomy for obesity. RESULTS:  The first patient did not respond to 5 mg per day of biotin, but taste was restored with 10 mg of biotin per day. Biotin was prescribed based on information that lipoic acid bound to the biotin transporter. Baseline urine gave no evidence of a pre-existing biotin deficiency. The second patient did not have restoration of taste after taking biotin 5 mg per day for 7 weeks but did have taste restoration on biotin 20 mg per day. Neither subject had an abnormal biotinidase level. CONCLUSIONS:  Further research into the relationship of biotin to taste is clearly indicated. Loss of taste was very distressing and significantly altered the quality of life for both patients. Since biotin up to 40 mg per day has been shown to be safe, a therapeutic trial of pharmacologic doses of biotin should be considered as a potentially curative treatment in patients who present with a loss of taste that has no obvious cause.

High-dose biotin, an inducer of glucokinase expression, may synergize with chromium picolinate to enable a definitive nutritional therapy for type II diabetes.
            (McCarty, 1999) Download
Glucokinase (GK), expressed in hepatocyte and pancreatic beta cells, has a central regulatory role in glucose metabolism. Efficient GK activity is required for normal glucose-stimulated insulin secretion, postprandial hepatic glucose uptake, and the appropriate suppression of hepatic glucose output and gluconeogenesis by elevated plasma glucose. Hepatic GK activity is subnormal in diabetes, and GK may also be decreased in the beta cells of type II diabetics. In supraphysiological concentrations, biotin promotes the transcription and translation of the GK gene in hepatocytes; this effect appears to be mediated by activation of soluble guanylate cyclase. More recent evidence indicates that biotin likewise increases GK activity in islet cells. On the other hand, high-dose biotin suppresses hepatocyte transcription of phosphoenolpyruvate carboxykinase, the rate-limiting enzyme for gluconeogenesis. Administration of high-dose biotin has improved glycemic control in several diabetic animals models, and a recent Japanese clinical study concludes that biotin (3 mg t.i.d. orally) can substantially lower fasting glucose in type II diabetics, without side-effects. The recently demonstrated utility of chromium picolinate in type II diabetes appears to reflect improved peripheral insulin sensitivity--a parameter which is unlikely to be directly influenced by biotin. Thus, the joint administration of supranutritional doses of biotin and chromium picolinate is likely to combat insulin resistance, improve beta-cell function, enhance postprandial glucose uptake by both liver and skeletal muscle, and inhibit excessive hepatic glucose production. Conceivably, this safe, convenient, nutritional regimen will constitute a definitive therapy for many type II diabetics, and may likewise be useful in the prevention and management of gestational diabetes. Biotin should also aid glycemic control in type I patients.


High-dose biotin may down-regulate hepatic expression of acute phase reactants by mimicking the physiological role of nitric oxide.
            (McCarty, 2003) Download
There is recent evidence that nitric oxide blocks IL-6 signaling in hepatocytes by inhibiting activation of Stat3. If this effect is mediated by cGMP, then high-dose biotin--which can directly activate guanylyl cyclase--may have the potential to suppress hepatic production of acute phase proteins.

cGMP may have trophic effects on beta cell function comparable to those of cAMP, implying a role for high-dose biotin in prevention/treatment of diabetes.
            (McCarty, 2006) Download
Incretin hormones have trophic effects on beta cell function that can aid prevention and treatment of diabetes. cAMP is the primary mediator of these effects, and has been shown to potentiate glucose-stimulated insulin secretion, promote proper beta cells differentiation by increasing expression of the crucial transcription factor PDX-1, and prevent beta cell apoptosis. cGMP's role in beta cell function has received far less scrutiny, but there is emerging evidence that it may have a trophic impact on beta cell function analogous to that of cAMP. An increase in plasma glucose boosts beta cell production of cGMP, which acts as a feed-forward mediator to enhance glucose-stimulated insulin secretion. cGMP also has an anti-apoptotic effect in beta cells, and there is now indirect evidence that it promotes expression of PDX-1. Supraphysiological concentrations of biotin can directly activate guanylate cyclase, and there is limited evidence that high intakes of this vitamin can be therapeutically beneficial in diabetics and in rodent models of diabetes. Beneficial effects of cGMP on muscle insulin sensitivity and on control of hepatic glucose output may contribute to biotin's utility in diabetes. The fact that nitric oxide/cGMP exert a range of favorable effects on vascular health should further encourage exploration of biotin's preventive and therapeutic potential. If an appropriate high-dose biotin regimen could achieve a modest systemic increase in guanylate cyclase activity, without entailing unacceptable side effects or risks, such a regimen might have considerable potential for promoting vascular health and preventing or managing diabetes.


 

In type 1 diabetics, high-dose biotin may compensate for low hepatic insulin exposure, promoting a more normal expression of glycolytic and gluconeogenic enyzymes and thereby aiding glycemic control.
            (McCarty, 2016) Download
In type 1 diabetics, hepatic exposure to insulin is chronically subnormal even in the context of insulin therapy; as a result, expression of glycolytic enzymes is decreased, and that of gluconeogenic enzymes is enhanced, resulting in a physiologically inappropriate elevation of hepatic glucose output. Subnormal expression of glucokinase (GK) is of particular importance in this regard. Possible strategies for correcting this perturbation of hepatic enzyme expression include administration of small molecule allosteric activators of GK, as well as a procedure known as chronic intermittent intravenous insulin therapy (CIIIT); however, side effects accompany the use of GK activators, and CIIIT is time and labor intensive. Alternatively, administration of high-dose biotin has potential for modulating hepatic enzyme expression in a favorable way. Studies in rodents and in cultured hepatocytes demonstrate that, in the context of low insulin exposure, supra-physiological levels of biotin induce increased expression of GK while suppressing that of the key gluconeogenic enzyme phosphoenolpyruvate carboxykinase. These effects may be a downstream consequence of the fact that biotin down-regulates mRNA expression of FOXO1; insulin's antagonism of the activity of this transcription factor is largely responsible for its modulatory impact on hepatic glycolysis and gluconeogenesis. Hence, high-dose biotin may compensate for subnormal insulin exposure by suppressing FOXO1 levels. High-dose biotin also has the potential to oppose hepatic steatosis by down-regulating SREBP-1 expression. Two pilot trials of high-dose biotin (16 or 2mg per day) in type 1 diabetics have yielded promising results. There is also some reason to suspect that high-dose biotin could aid control of diabetic neuropathy and nephropathy via its stimulatory effect on cGMP production. Owing to the safety, good tolerance, moderate expense, and current availability of high-dose biotin, this strategy merits more extensive evaluation in type 1 diabetes.

Pharmacokinetics and pharmacodynamics of MD1003 (high-dose biotin) in the treatment of progressive multiple sclerosis.
            (Peyro Saint Paul et al., 2016) Download
INTRODUCTION:  Multiple sclerosis (MS) is a chronic, potentially highly disabling neurological disorder. No disease-modifying treatments are approved in the progressive and not active forms of the disease. AREAS COVERED:  High doses of biotin were tested in an open-label pilot study involving 23 patients with progressive MS and reported positive results. A randomized, double-blind, placebo-controlled trial in 154 progressive MS patients confirmed the beneficial effect of MD1003 (high-dose biotin) on reversing or stabilizing disability progression, with a good safety profile. It is proposed that MD1003 in progressive MS 1) increases energy production in demyelinated axons and/or 2) enhances myelin synthesis in oligodendrocytes. Biotin is highly bioavailable; absorption and excretion are rapid. The major route of elimination is urinary excretion. EXPERT OPINION:  A high oral dose of biotin seems generally well tolerated but a few important safety concerns were identified: 1) teratogenicity in one species and 2) interference with some biotin-based laboratory immunoassays. The animal toxicity data are limited at such high doses. Further preclinical studies would be useful to address the mechanism of action of MD1003. Assessment of clinical benefit duration in responders will be also very important to set. Results of randomized, placebo-controlled trial are reassuring and provide hope for the treatment of progressive MS.

MD1003 (high-dose biotin) for the treatment of progressive multiple sclerosis: A randomised, double-blind, placebo-controlled study.
            (Tourbah et al., 2016) Download
BACKGROUND:  Treatment with MD1003 (high-dose biotin) showed promising results in progressive multiple sclerosis (MS) in a pilot open-label study. OBJECTIVE:  To confirm the efficacy and safety of MD1003 in progressive MS in a double-blind, placebo-controlled study. METHODS:  Patients (n = 154) with a baseline Expanded Disability Status Scale (EDSS) score of 4.5-7 and evidence of disease worsening within the previous 2 years were randomised to 12-month MD1003 (100 mg biotin) or placebo thrice daily, followed by 12-month MD1003 for all patients. The primary endpoint was the proportion of patients with disability reversal at month 9, confirmed at month 12, defined as an EDSS decrease of ⩾1 point (⩾0.5 for EDSS 6-7) or a ⩾20% decrease in timed 25-foot walk time compared with the best baseline among screening or randomisation visits. RESULTS:  A total of 13 (12.6%) MD1003-treated patients achieved the primary endpoint versus none of the placebo-treated patients (p = 0.005). MD1003 treatment also reduced EDSS progression and improved clinical impression of change compared with placebo. Efficacy was maintained over follow-up, and the safety profile of MD1003 was similar to that of placebo. CONCLUSION:  MD1003 achieves sustained reversal of MS-related disability in a subset of patients with progressive MS and is well tolerated.

 


References

Fuhr, JP, et al. (2005), ‘Use of chromium picolinate and biotin in the management of type 2 diabetes: an economic analysis.’, Dis Manag, 8 (4), 265-75. PubMed: 16117721
Greenway, FL, et al. (2011), ‘Loss of taste responds to high-dose biotin treatment.’, J Am Coll Nutr, 30 (3), 178-81. PubMed: 21896875
McCarty, MF (1999), ‘High-dose biotin, an inducer of glucokinase expression, may synergize with chromium picolinate to enable a definitive nutritional therapy for type II diabetes.’, Med Hypotheses, 52 (5), 401-6. PubMed: 10416947
——— (2003), ‘High-dose biotin may down-regulate hepatic expression of acute phase reactants by mimicking the physiological role of nitric oxide.’, Med Hypotheses, 61 (4), 417-18. PubMed: 13679004
——— (2006), ‘cGMP may have trophic effects on beta cell function comparable to those of cAMP, implying a role for high-dose biotin in prevention/treatment of diabetes.’, Med Hypotheses, 66 (2), 323-28. PubMed: 16309850
——— (2016), ‘In type 1 diabetics, high-dose biotin may compensate for low hepatic insulin exposure, promoting a more normal expression of glycolytic and gluconeogenic enyzymes and thereby aiding glycemic control.’, Med Hypotheses, 95 45-48. PubMed: 27692165
Peyro Saint Paul, L, et al. (2016), ‘Pharmacokinetics and pharmacodynamics of MD1003 (high-dose biotin) in the treatment of progressive multiple sclerosis.’, Expert Opin Drug Metab Toxicol, 12 (3), 327-44. PubMed: 26699811
Tourbah, A, et al. (2016), ‘MD1003 (high-dose biotin) for the treatment of progressive multiple sclerosis: A randomised, double-blind, placebo-controlled study.’, Mult Scler, PubMed: 27589059