My Research and Thoughts
When I started this it was a pretty quick read. Now it is getting a bit long so I have added a bit of a contents list which will jump you to the relevant section if you click on them.
The Importance of Delayed Release (DR) Capsules with Biotin:
Vitamin B group (the water soluble vitamins).
It has long been understood that B vitamins are involved with breaking down Carbohydrates and proteins into energy an amino acids needed to build healthy hair, nails and nerves.
The B group of vitamins are all water soluble vitamins, meaning that unused quantities are not stored in the body for later use, but rather continually flushed out by the liver in urine. This necessitates that they are continually replaced by your diet so that they are available when your body needs them. Many of these are involved in converting Proteins into energy and other building blocks (amino acids).
Vitamin B's, in particular, are linked to brain and nerve performance. Of particular interest at the moment is Vitamin B7 (H) or Biotin.
The effects of Biotin
Biotin (also known as vitamin H) is part of the B-complex group of vitamins that help the body convert food into fuel. Healthy skin, hair, eyes, and liver depend on B-complex vitamins, and, according to the University of Maryland Medical Center’s website, “They also help the nervous system function properly.”
Although it’s rare to be biotin-deficient, symptoms can include hair loss, dry eyes, dry or scaly skin, fatigue, and insomnia. Certain conditions such as Crohn’s disease can lead to biotin deficiency due to problems with vitamin absorption.
Since there is potential for drug interaction, you should consult your doctor before you start supplementing with biotin.
Long-term use of antibiotics can kill certain gut bacteria responsible for biotin production, and anti-seizure medications can lower biotin levels in the body.
Even in high doses, this water-soluble B vitamin doesn’t have any known side effects and is considered to be nontoxic.
French Neurologist Frederic Medel (amongst others) under the Pharmaceutical company MedDay are currently running trials. Measuring how Biotin effects different symptoms of Progressive forms of Multiple Sclerosis (PPMS and SPMS). Here is the Manuscript they submitted to (and was accepted by) Neuropharmacology Journal which forms the crux of their theories and research. In which they hypothesize "that high dose Biotin is exerting a therapeutic effect in patients with progressive MS through two different and complementary mechanisms: by promoting axonal remyelination by promoting myelin production and by reducing axonal hypoxia through enhanced energy production". In short (and laymen terms), the two mechanisms are repairing the insulation around the nerves (the myelin) and increasing nerve signal strength (turning the voltage up to make the light bulb glow brighter).
Now I theorise that for most, sufficient levels of vitamins are obtained from a balanced diet. But for many we need help, and take supplements in all shapes and forms. Some of us need more of one and less of another and I feel we are starting to see this being linked to genetics, being more or less predisposed to certain ailments, such as cancers, MS etcetera.
The recommended daily Intake (or allowance, RDI/RDA) for Vitamin B7 (Biotin) is 10-30 mcg in most countries around the world. That is 10 micro grams, 10/1,000,000 of a gram.
10 mg, that's 10 milligrams (1000 times the RDI) has been provided as a dietary supplement for many years to help with hair, nail and skin care. Mainly promoted as helping with hair regrowth.
The French Pharmaceutical company have been trialing 100-500 mg for use in treating Progressive forms of Multiple Sclerosis. 100mg is 10,000 times the RDI. Or 10 times what is already readily available as a dietary supplement for promoting hair growth.
I have been taking between 225 and 300mg a day for over 4 years now (Jun 2018). At first I took 100mg, three times a day. I found this a little harsh on my stomach. Additionally my research indicated unused quantities of the water soluble B vitamins are rapidly flushed out of the body in urine. A clear example of this is demonstrated by taking a multivitamin complex containing Riboflavin (another of the water soluble B vitamins, B2). It has a bright yellow colour and has the effect of turning urine bright yellow as unused quantities are flushed out of the body by the liver. A clear (or rather bright yellow) Indication of how excess of the water soluble vitamins are flushed out and wasted. So I started taking 75mg of Biotin 4 times a day. I have found this easier on my system, and hopefully better utilised. As my research progressed I also found that drinking a lot of water with each capsule helps absorption. The two natural forms of Biotin we are exposed to are typically bound to protein molecules in the food we consume. It is also produced by gut bacteria in similar forms (Hamid M. Said. J Nutr. 2009 Jan; 139(1): 158–162.). These forms of natural biotin are acted on by enzymes in our gut, breaking the biotin-protein bond and creating "free biotin" or more correctly ionised biotin. This charged biotin is then transported across the gut wall by system referred to as the sodium-dependent multivitamin transporter (SMVT). But these two natural forms of biotin are not what we are using to supplement our biotin intake. We use pure biotin, not free or ionised biotin. Without a charge it can not be transported in this manner and has to be completely dissolved and absorbed with water. Although Biotin is classed and one of the water soluble B vitamins, its solubility is very low compared with other B vitamins. 100mg of pure biotin requires about 500ml (1/2 litre) of water to completely dissolve at STP (220 mg/L (at 25 °C) PubChem). Hence why you should always drink at least 1 glass of water with each 100mg of pure biotin consumed. Preferable two glasses. Another reason why I encourage 75mg doses not 100mg.
As my research into biotin has progressed I wondered why MedDay use a substance in their capsules that indicates a controlled release capsule. Hypromellose (hydroxypropyl méthylcellulose) E464. Why would they do this? Well its quite obvious really. There is a lot of research on the stability of pure biotin (C10H16N2O3S). It is considered a very stable compound in both acid and alkaline solution. Except when it comes to Hydrochloric Acid (HCL), which readily breaks down pure biotin. What is the acid in our gastric juices? Yes, HCL! So we are now putting all our biotin products in Delayed Release (DR) capsules which release the contents of the capsule towards the end of the stomach, at the beginning of the small intestine where the biotin can be absorbed without being broken down by the HCL in the stomach. So DR capsules are absolutely critical to maximising the amount of biotin being presented to the small intestine for absorption.
A useful comment at this point is how to identify a good form of Biotin you buy in either a concentrated, powered form or what grade of Biotin has been used in capsule or pill production.
In brief, to qualify as Pharmaceutical Grade, the pure Biotin must conform the following measures. It must be :
Greater than 97.5% pure,
Have a specific rotation of between +89 and +93 degrees,
Have not more than 2% impurities
There are a lot of other measures that it must conform to, to be considered fit for human consumption. For our purpose, when selecting a biotin these are the most important.
What I call the Ultra High Grade of biotin that we use in most of our products is specifically manufactured at the top of the acceptable range that is considered acceptable for a Pharmaceutical Biotin. What I call a standard Pharmaceutical grade is one that has been manufactured to fit anywhere in the acceptable range.
A biotin manufactured to have purity greater than 97.5% is far cheaper to make than a biotin that is made to be greater than 99% pure. I hope for obvious reasons.
Always ask for a Certificate of Analysis (CoA) from the manufacture of the Biotin. It is also useful to see a retest certificate that on-sellers/repackages sometimes have done. CoA’s are pretty standard and should include an Impurities field. This is usually measured in an identifier like "NMT 2%" Meaning Not More Than 2%. Here's a typical Certificate of Analysis (CoA). This tells you that it is 99.44% pure. There are two main standards that are used to govern the quality of chemicals manufactured for human consumption, USP and FCC. The specification for a Pharmaceutical (Pharma) grade under the current USP standard is 97.5-102% pure and FCC is 97.5-100.5%. As you can see FCC has a tighter specification than USP. Here we will only discuss USP standards unless otherwise stated. Manufacturing costs increase exponentially the closer the manufacturer gets to 100% pure. However, CoA's do not tell you everything you need to know about the Biotin you are buying.
Biotin is a chemical compound with the formula C10H16N2O3S. The compound is known as an isomer, as it can exist in different forms with the same chemical makeup. There are different types of isomers, structural and positional to name a couple but I won't go into this detail here. Biotin can take the form of eight different isomers which have the same chemical makeup, but with different geometry at three of the Carbon atoms at the centre of the molecule. An easy way it was explained to me was like having a left and right hand versions. Both are identical, just mirror images of each other. But with Biotin there are 8 of them. Some of these occur naturally and some don't. Each of the naturally occurring isomers have different levels of biological availability to different organisms. As far as I can tell, the term D-Biotin is used rather generically to describe all the naturally occurring forms which can have from zero to around 50% biologically activity. A more accurate designation given to a more biologically active form appears to be one identified as d-(+)-biotin. That is d not D, there is a difference I found out recently, d has the same meaning as + and refers to a positive spin on reflected polarised light, whereas D refers to the geometry of a molecule (left hand/ right hand).
Biotin Manufacturing: Biotin is manufactured using several different methods. Some are purely chemical in nature others are a combination of natural (using biological organisms to create the biotin) and chemical and mechanical methods to extract and purify the biotin. By controlling things like moisture, pressure, heat, light, and other radiation sources etcetera during the manufacturing processes, concentration of the different isomers in the finished product can be influenced. The tighter the manufacturing is controlled, the more consistent the finished product will be. Generally a manufacturer will test multiple samples to confirm purity etc. and their testing gives a much more accurate result than a one off test that an on-seller might get done. So always ask to see the manufacturers CoA as a one off retest certificate is inaccurate and only good to indicate that the manufacturers goods are what they say they are.
How to gauge biological availability? Scientists have worked out that if you expose a Right handed or a Left handed isomer to polarised light, it will reflect the light in either a positive (d, +) or negative (l,-) direction (Clockwise or Anticlockwise). With biotin, they have determined that the isomers that reflect polarised light in a positive (clockwise) direction coincide to those with higher growth rates in certain organisms. Hence, they are said to be biologically active forms of biotin. Which are most biologically active for humans? I don’t think we really know as I have not been ably to locate any papers that investigate this, but the specification used to designate a pure biotin as a Pharmaceutical Grade of biotin defines a specific rotation of between +89 to +93 degrees.
Now I make a concerted effort to ensure the type that is used in our formulations is always greater than 99% pure and has a specific rotation greater than 92 degrees whenever possible. The biotin we uses for most of our high biotin products is right at to top end of the specification used to define Pharma grade biotin, both in terms of purity and specific rotation. I have found that some suppliers are not able to tell what version of Biotin they supply is. Or even that that they are aware there is a difference. Only that the biotin they use is Pharmaceutical Grade. The only product at this stage that we not use an Ultra High Pharmaceutical Grade of biotin is our MS-High Biotin. For this we use a Standard Pharmaceutical grade of biotin, which is significantly cheaper as the manufacturer does not have to have such tight manufacturing controls in place.
So, in brief, the Biotin we use for most high Biotin products is what we refer to as an Ultra-High Pharma Grade and is manufactured to always be at the top end of the USP specification. There is another little secret that renders our Ultra Grade biotin easier for the intestine to absorb at such high concentrations but I am not quite ready to share that yet.
The Biotin we use for our cheaper high biotin product, MS-High Biotin, is a Standard Pharmaceutical Grade and can be anywhere in the USP specification.
The biotin molecule binds to a molecule called streptavidin very effectively. Many blood tests use streptavidin binding assays as part of their testing processes. As such, you should tell your Doctor before doing any blood or urine tests and stop taking biotin at least 5 days before giving blood or urine samples. Here is a list of tests that may be effected and some more interesting information regarding streptavidin binding of biotin.
My MS and Biotin
Since using the right (or as far as I can tell) the right Biotin my Multiple Sclerosis symptoms feel less pronounced. The most significant being my energy levels. I clearly do not suffer as much from fatigue. I can work longer hours physically and mentally and function at a higher level. More like my old self. Not feeling fatigued as much has made me faster, stronger and sharper again. Which maybe has also helped with my state of mental wellbeing. Other side effects from the MS-BIOTIN COMPLEX have all been good. My hair and skin have never looked better! My small bald batch I have been developing over the past 10 years seems to be diminishing. My skin has been commented on, by women, looking younger. Most importantly, regarding my MS, I have not felt this good in many years. I am now taking our MultipleSupplements BIOTIN COMPLEX four times a day and our MultipleSupplements PROBIOTIC formula once a day and recommend this to anyone wanting to try dietary supplements that may help bolster their neurological an intestinal systems.
Our MS-Biotin Complex also contains Vitamin D3, the sunshine vitamin. Which most multivitamin complexes do not contain.
Before I go into this a word of caution. High doses of vitamin D can cause ireversible kidney damage and other negative side effects such as weakening of the bones. DO NOT take high doses of Vitamin D without a health care professional monitoring you.
I have been taking Vitamin D at around 10,000IU/day for about 10 years. The more research I do the more I think it has slowed the progression of the disease over the past 16 years since diagnosis. About 12 months ago I came across Dr Coimbra and the work he has been doing over the past 15 years with Vitamin D in treating immune diseases.
Dr Coimbra is based in Sao Paulo, Brazil. He is a professor at the University there, has held many positions at the main hospital (in neurilogical capacities) and has published numerous papers.
For the past 15 years or so he has been working on using vitamin D in treating various imune diseases, in particular Multiple Sclerosis (MS). It is reputed that he has treated 1000,s of MS patients in Bazil with sucess rates in halting the disease, and even reversing it, in the 90 percent range. With minimal negative side effects if minitored and doses adjusted corectly. To the point where he now has developed a protocol that he is teaching other Dr's around the world to use.
I see two neurologist here in NZ neither of which were interested in helping me with this protocol. Fortunately my GP was more open to the idea. Which his help and under the guidance of a Dr schooled in the protocol I hope to start it soon (written late Nov2016).
Watch this space for updates and here are some useful links.
ALA and why the interest for MS?
Lipoic acid (LA), also known as α-lipoic acid and alpha lipoic acid (ALA) and thioctic acid is an organosulfur compound derived from caprylic acid (octanoic acid). ALA is made in animals normally, and is essential for aerobic metabolism. It is also manufactured and is available as a dietary supplement in some countries where it is marketed as an antioxidant, and is available as a pharmaceutical drug in other countries.
Alpha Lipoic Acid (ALA) is being trialed for use with MS. It should not be confused with the Omega Fatty Acid, Alpha Linolenic Acid also sometimes referred to as ALA which is commonly found in Flax Seed Oil.
ALA exists in two different isometric forms. Much like Biotin exists in 8 different forms. The two isomers of ALA are referred to as R-ALA and S-ALA. Only the R-ALA is biologically active but unstable when it is not mixed with its partner S-ALA.
ALA is currently available as a dietary supplement in two forms. Most commonly as a Racemix ALA which is typically a 50/50 mix of R-ALA and S-ALA. Also referred to as R/S-ALA. It can also be sourced as a purified R-ALA. Some suppliers claim they have stabilised the compound and taking stabilised R-ALA is far more effective than taking a typical racemic ALA. I am not aware of any trial having been done on this and all the Trials on MS have been conducted using 1200mg of Racemix ALA per day. Either one dose of 1200mg or two doses of 600mg. I choose to take two 600mg capsules after Breakfast to get it out of the way.
Existing trials indicate doses of 1200mg ALA/day are well tolerated with main negative side effect reported to be gastrointestinal disorders. Some good probiotics may help to minimise this effect. To my knowledge at time of writing 5 trials have been conducted and a sixth is currently enrolling. More details below.
The uptake of ALA across the intestinal wall utilizes the same mechanism as Biotin. The Sodium dependant MultiVitamin Transporter (SMVT). Studies have demonstrated when taking biotin at normal levels the uptake of each is affected. Hence I recommend you not to take Biotin and ALA within two hours of each other. Preferably separated by food so there is less likelihood for one to affect the uptake of the other.
How to take it:
I take my first Biotin when I wake with a glass of water. The ALA I take two, 600mg capsules, after breakfast. Then another Biotin between Lunch and Dinner (usually around 2pm), with a glass of water. My third and last Biotin just before bed, again with a glass of water. I take 75mg capsules (MS-Biotin Complex) so that's 225mg/day fo Biotin. Depending on how my fatigue is feeling I might ad a 4th capsule before lunch.
An early pilot study compared oral lipoic acid given at different doses to 37 MS patients over a two-week period. The treatment was well-tolerated and appeared to reduce the level of T-cell migration into the brain and spinal cord. Results were published in the Scientific Journal Multiple Sclerosis in 2005.
Another pilot study with 51 patients explored the effect of lipoic acid compared to a placebo in patients with secondary progressive multiple sclerosis (SPMS) over a two-year period. The results were positive, with the treatment reported to have reduced the speed of brain tissue loss and improved patients’ walking speed. Data were presented at the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) Congress and the 68th annual American Academy of Neurology meeting in 2016.
A Phase 1 trial (NCT00997438) completed in 2016 aimed to assess the potential benefit of lipoic acid in patients with relapsing-remitting MS (RRMS) and SPMS, as well as observe how lipoic acid is broken down in the body in both MS patients and healthy participants. No serious adverse events or notable side effects were observed.
A Phase 2/3 trial (NCT01188811) to determine whether lipoic acid can protect the brain and slow disability in people with SPMS finished in 2016. Reported results showed a reduction in brain atrophy, suggesting it could play a neuroprotective role in SPMS. Lipoic acid was also found to be safe and well-tolerated; noted side effects were gastrointestinal.
A Phase 2 trial (NCT02133664), completed in 2017, aimed to determine whether lipoic acid and omega-3 fatty acids can improve cognitive function in RRMS or SPMS patients. Participants were randomly assigned lipoic acid and omega-3 fatty acids or a placebo for a period of 12 weeks. The ability to perform a range of cognitive tests was assessed at the start and end of the trial, and data compared. Results did not suggest that the treatment provides a significant benefit to cognition after 12 weeks.
A Phase 2 trial (NCT03161028) in progressive MS patients is planned but not yet enrolling participants. The U.S. trial aims to assess the neuroprotective capability of lipoic acid compared to placebo over two years. Neuroprotection will be evaluated through changes in measures of brain volume, as captured in magnetic resonance imaging (MRI) scans. Changes in mobility will also be evaluated using the timed 25-foot walk test and the 2-minute timed walk test.
Other useful Information
I have put a few other links to knowledge on the web that I feel are relevant to my MS diet and dietary supplements below. Other information I find an updates on the progress I continue to make I will add to my blog.
Over coming MS - George Jellineck. A read I recommend to anyone diagnosed with Multiple Sclerosis. WebSite is here. Which recommends a diet much like Dr Swank but makes it a little easier to follow.
Biotin is already sold as a dietary supplement at 1000 times the Recommended Daily Intake (10,000 mcg) so it is only a small step to 100,000 mcg. I also liken it to Vitamin D which is recommended for people with MS to take in high doses well over the Recommended Daily Intake.
Is it safe? I don't know, but it looks like there are probably 1000's of people already taking it by them selves at 300,000 mcg/day. In all my reading I only came across one mention of a "life threatening" case involving Biotin, see here, and as they state, "Because of the potential for interactions, dietary supplements should not be taken with medication without first talking to an experienced healthcare provider." For me, as I said I feel great and haven't had any issues. I currently take Copaxone as my disease modifying drug.
A bit about my back ground
Born in the UK in 1968 to an English mother and Kiwi father, we emigrated to NZ when I was 12 with my younger brother, two older brothers staying in the UK.
I grew up and was schooled at Auckland Grammar and eventually trained as a mechanical engineer (although I haven't practiced engineering for a long time now!). I met my wife to be and we moved to the clean, green Waikato in the mid 90's where we have been, on and off, ever since.
I got a job designing rock crushing equipment for a small NZ manufacturer which became part of a large global organisation. I held various roles from product research and development, product Management through to Vice President Sales and Marketing. I have my name on various patents and have published papers on innovations in NZ. You can read more of my career in my LinkedIn profile if interested.
I finished up a contract as Vice President of Construction for Metso based in Brisbane Australia towards the end of 2010 and returned to New Zealand. Where I held a number of short term roles involving research, innovation and commercialisation, before setting up my own consulting firm.
I attribute my success in Engineering research and product development to my incessant need to understand why things are the way they are. Understanding the science behind why things work the way they do.
I now consult to various industries, providing market evaluation, business planning and commercialisation services. Specialising in businesses wanting to launch new products, services, or open up new markets for existing products.
The more I read and researched about MS and supplements, the more I needed to know. This is when I started my serious research into dietary supplements culminating in establishing MultipleSupplements.com.
Thanks for reading.
My quote: Human biochemistry is so incredibly complicated I think it will take a bigger brain that the human brain before it is fully understood