The most important aspect of vitamin B5 in the context of CoA, is that the CoA is necessary for generating acetyl-CoA. One way in which acetyl-CoA is synthesized, is during the first step of the citric acid cycle, where pyruvate is converted to acetyl-CoA. This again means that without both vitamin B5 and vitamin B1, we cannot produce acetyl-CoA in the context of the citric acid cycle. However, acetyl-CoA can also be generated from lipid, and amino acid breakdown. Without vitamin B5 though, we would not have the necessary CoA to even generate acetyl-CoA from these alternate pathways. This means that when we are talking about acetyl-CoA, vitamin B5 is an incredibly essential component!

Acetyl-CoA is used for lots of different processes throughout the body and brain. As we already discussed in the vitamin B1 section, acetyl-CoA provides the acetyl groups that are required by the enzyme choline acetyltransferase to synthesize the neurotransmitter acetylcholine. Furthermore, acetyl-CoA also feeds the mevalonate pathway, which synthesizes the cholesterol necessary for all steroid hormone synthesis. The mevalonate pathway is also responsible for producing lots of other important compounds, such as coenzyme Q10 and vitamin K. Thus, it clearly cannot be understated just how important vitamin B5 is for providing that incredibly ubiquitous CoA!

Pantothenic acid also plays an important role in skin health. Through various mechanisms, pantothenic acid can help enhance skin hydration and healing. This is a great combination of effects when it comes to promoting skin health, and thus it is no surprise that vitamin B5 is often best known for its skin benefits. In fact, it is often included in topical skin care products. However, even oral supplementation of pantothenic acid can have positive benefits on our skin!

Similar to vitamin B1, we felt that vitamin B5 is a major contributor to the energizing effects and nootropic effects of a B-complex. With this in mind, we dosed the vitamin B5 at a fairly high level. This has the benefit of both maximizing the energizing effects of infini-B, in addition to providing a very nice effect on our skin! In terms of the form of vitamin B5 we decided to go for, we went for D-calcium pantothenate. This form of vitamin B5 is very stable, and has great absorption.

L-tryptophan is converted to 5-hydroxytryptamine (5-HTP) by the enzyme tryptophan hydroxylase, and 5-HTP is then converted to serotonin by AADC. Serotonin is then eventually further converted to the important circadian hormone, melatonin. This means that without vitamin B6, serotonin and by extension, melatonin could not be synthesized! Dopamine follows a similar pathway, by which the dietary amino acid L-tyrosine is converted to L-dopa by tyrosine hydroxylase. This L-dopa is then converted to dopamine by AADC. Dopamine is then eventually further converted to norepinephrine. This means that without vitamin B6, both dopamine and norepinephrine could not be synthesized!

Vitamin B6, via its active form, P5P, also acts as a cofactor for another important neurotransmitter synthesizing enzyme called glutamic acid decarboxylase (GAD). GAD catalyzes the conversion of the excitatory neurotransmitter glutamate to the inhibitory neurotransmitter GABA. Perhaps most importantly here, is that GAD acts as a way to get rid of the excitatory neurotransmitter glutamate, thus, without vitamin B6, our balance of excitatory glutamate to inhibitory GABA would be way off. This would result in negative effects on mood, and the general health of our brains.

Vitamin B6 also plays a major role in energy metabolism, most notably as a cofactor for the enzyme, glycogen phosphorylase. This enzyme breaks down glycogen, which is a compound that is used by the body to store energy. Glycogen is most notably stored in our muscles, and when we need a quick burst of energy production, glycogen is rapidly broken down into glucose, which can then eventually turn into usable energy. Since glycogen phosphorylase is necessary for this process, it means that vitamin B6 is crucial for utilizing glycogen stores. This is one of the reasons why vitamin B6 is quite popular for athletes. This will especially be true in the context of some of the other B-vitamins in Infini-B which help turn glucose into energy, like vitamin B1 and B5!

Considering vitamin B6’s effects on neurotransmitter synthesis and glycogen utilization, it is one of the more noticeable B-vitamins. Due to this, we wanted to include a solid dose of vitamin B6, in order to make infini-B feel as palpable as possible. However, the one issue with dosing vitamin B6 higher, is that it is one of the B vitamins which can have negative effects in higher doses. This is especially true for the basic form of vitamin B6 most often found in supplements, called pyridoxine HCL. Due to the bioavailability and safety issues with pyridoxine HCL, we skipped this form of vitamin B6. Instead, we went for the active form of vitamin B6, P5P, which can actually be supplemented orally! P5P can be supplemented at much higher doses, yet caution should still be taken. Due to this, we included a very solid, yet reasonable dose of P5P in Infini-B.

Biotin is a cofactor for five different carboxylase enzymes, these enzymes are:

1. Acetyl-CoA carboxylase alpha

2. Acetyl-CoA carboxylase beta

3. Pyruvate carboxylase

4. Methylcrotonyl-CoA carboxylase

5. Propionyl-CoA carboxylase

These enzymes are very important to the synthesis of long chain fatty acids and glucose, in addition to the metabolism of pyruvate and propionyl-CoA. The fatty acid synthesizing activity of these enzymes, likely underlies the majority of biotin’s effects on our skin. Our skin needs a constant supply of fatty acids to maintain skin barrier function, in addition to aiding in skin hydration. Thus, it is no surprise that deficiencies in biotin oftentimes first present themselves as skin dryness and rashes. However, herein lies also the double-edged sword of biotin. Our sebaceous glands have quite a bit of acetyl-CoA carboxylase (ACC) enzyme activity, which we need biotin for as a cofactor. ACC produces the fatty acids which later become incorporated in the structure of sebum. The right amount of sebum is incredibly important to skin health, however, larger amounts of sebum can result in acne. Due to this, it is perhaps not surprising that excessive intake of biotin can cause breakouts. In fact, research has actually looked at inhibiting ACC in order to benefit skin aesthetics. Thus, there is a fine balance in the level of biotin we want in our bodies.

With the double-edged sword activity of biotin on our skin in mind, we spent quite a bit of time trying to get the biotin dosage right. We found that lots of B-vitamin formulations which are currently on the market, likely provided much too high a dose of biotin. In fact, we found a lot of anecdotal reports around the web, which indicated various B-complex vitamins causing skin issues. Considering that we get plenty of biotin from our diets, it seemed best to be as prudent as possible with our biotin dosing. We still wanted to include biotin, because it is clearly very important for our body, skin, hair and nails, so we went with a mere 30 microgram dose. This is 100% of the biotin RDI, thus providing plenty of biotin, yet not enough to cause skin issues. This may seem like a very small dose of biotin, when other brands are including doses that are more than ten times as high, but based on our R&D effort, we determined this dose would slot the best into our B-complex because skin health is very important to us! In terms of the dosing form, we went for plain old D-biotin. This form appears to absorb just fine, and with the potential negative skin effects associated with high biotin levels, we decided it wasn’t logical to chase down biotin forms with highly enhanced absorption.

Vitamin B9 also has a significant effect on neurotransmitter synthesis, due to its role in helping to synthesize and recycle tetrahydrobiopterin (BH4). BH4 is a cofactor that is used by various neurotransmitter synthesizing enzymes. For example, the enzyme which turns dietary L-tryptophan into 5-hydroxytryptamine (5-HTP) in the first step of serotonin synthesis, tryptophan hydroxylase, requires BH4 as a cofactor. Similarly, the tyrosine hydroxylase enzyme, which catalyzes the first step in dopamine synthesis, also requires BH4 as a cofactor. As you may remember, from the vitamin B6 section, the second step in serotonin and dopamine synthesis, is catalyzed by aromatic L-amino acid decarboxylase which requires vitamin B6 as a cofactor. This means that neurotransmitter synthesis is highly dependent on the synergistic action of B-vitamins! Vitamin B9 helps synthesize BH4 by acting as a cofactor for the enzyme dihydrofolate reductase. This enzyme converts the inactive dihydrobiopterin (BH2), to the active BH4 form. When BH4 is being used as a cofactor for tyrosine and tryptophan hydroxylase enzymes, BH4 turns into BH2. Thus, vitamin B9’s role in converting BH2 back to BH4, has a very positive effect on neurotransmitter synthesis. With this in mind, it is no surprise that low vitamin B9 levels have also been linked to low mood! BH4 is also an important cofactor in the synthesis of nitric oxide from L-arginine. Due to this, vitamin B9 has a two pronged effect on cardiovascular function, by reducing homocysteine levels and aiding in the synthesis of nitric oxide!

When it comes to dosing vitamin B9, we do have to be careful. Adequate amounts of vitamin B9 are required to power some of the most important functions in our body, however, higher doses of vitamin B9 can actually backfire and start to cause negative effects on our DNA. This is one of the reasons why we purposefully dosed vitamin B9 on the lower side of the spectrum, in order to maximize its benefits. Another strategy we employed to get the most out of vitamin B9, was to use its already methylated active form, called L-5 methyltetrahydrofolate (L-5-MTHF). This form of vitamin B9, in stark contrast to the commonly used folic acid, does not need to be methylated in order for it to become active. This means that L-5-MTHF is one of the best forms of vitamin B9 when it comes to enhancing our bodies' methylation ability!

As we mentioned already in the vitamin B9 section, vitamin B12 is also incredibly important for the process of methylation. Vitamin B12, similarly to vitamin B9, helps shuttle methyl groups around the body. Most importantly, it works hand in hand with vitamin B9 to methylate homocysteine, thereby converting it to methionine, which can then be used to synthesize S-adenosylmethionine (SAMe), one of the most important methyl donors. The methylation of homocysteine is carried out by an enzyme called methionine synthase, of which two forms exist. One of the forms uses vitamin B12, in the form of methylcobalamin, as a cofactor. With vitamin B12’s methylation effects in mind, it is of course no surprise that it is also very important for DNA synthesis and repair!

One of the most important effects of vitamin B12 is likely its effects on myelin. Myelin is a primarily lipid based compound, which forms an electrically insulating layer around the axons of our neurons. This myelin covering of the axons, is commonly referred to as the myelin sheath. Within this myelin sheath, there are small gaps, called the ‘nodes of ranvier’, which help accelerate signals through the axons of our neurons. If this myelin sheath starts to degrade, electrical signals can less readily pass through our neurons, and thus, we would experience drastically decreased neurological function. Since vitamin B-12 plays a critical role in the maintenance of the myelin sheath, this is more than likely its most important function and part of the reason why B-12 is so popular amongst nootropic enthusiasts!

The benefits of vitamin B-12 are most pronounced if it is being supplemented far beyond its recommended daily intake value. What’s nice about B-12, is that even in these very high doses, it is safe, and thus we can boost the level of B-12 quite significantly in order to optimize the cognitive effects of Infini-B. Vitamin B12 can also be supplemented in multiple different forms. The most common form seen on the market is cyanocobalamin, however, this form has fairly poor bioavailability. One of the most popular forms of vitamin B-12 is methylcobalamin, due to its high bioavailability, and because it is one of the active forms of vitamin B-12. However, it is often incorrectly thought that because methylcobalamin is methylated, that this form of vitamin B-12 is the best for methylation. This is not entirely true, because it appears that the methyl group of supplemented methylcobalamin does not actually participate in any methylation reactions. What appears to be most important for vitamin B-12 supplementation, is that the vitamin B-12 is readily absorbed and retained. Methylcobalamin has these two attributes, and so does hydroxocobalamin. Both of these forms may absorb through slightly different pathways, and due to this, we decided on a 50/50 split of both methylcobalamin and hydroxocobalamin for our vitamin B-12 component. This is the exact blend many of you have come to love over the years in our super B-12 formulation!