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Synergy of supplements, part 1 – Forskolin and PDE-4 inhibitors

Appropriate combination of substances allows one to intensify their operation or extend their spectrum of applications. The use of synergy of action of various substances is the basis of advanced supplementation, which lies at the base of the perfectly perceptible effects of complex pre-workout, fat-burning or nootropic preparations. In this series of articles we will try to analyse the most popular combinations of supplements and check which mechanisms are responsible for their synergy.

At first, let’s talk about Forskolin, which is combined with agents that inhibit the activity of phosphodiesterase 4. It’s customary for this to use artichoke extract, although this is not the only option worth our attention. First, however, let’s analyse the interaction itself, and let’s choose the ingredients at the end.

Thus, the flagship effect of Forskolin is the enhancement of cAMP growth in cells. This is due to fat burning, testosterone-enhancing effects, reducing asthma and pro-cognitive symptoms. cAMP increases due to the effect of Forskolin on the increase of adenylate cyclase activity. Despite the fact that the most often uses for Forskolin to reduce excess fat, we will deal with the aspect affecting cognition and the efficiency of the mind.

Phosphodiesterases are enzymes that are designed to break down cyclic nucleotides inside cells, including cAMP. Inhibition of these enzymes results in an increase in cAMP in cells. The artichoke extract, which we have already mentioned, contains substances that are non-selective PDE inhibitors. One of these substances is luteolin. It inhibits the PDE-4 subtype, among other things, which is the most interesting form for us.

Cyclic adenosine monophosphate is a secondary transmitter that transmits information inside the cell. The fourth type of phosphodiesterases has activity in cells of the immune and nervous system. Neural cAMP mediates the short- and long-term aspects of synaptic transmission. Studies show that supplementing Forskolin with a PDE-4 inhibitor results in improved long-term memory. Pharmacological PDE-4 inhibitors are also used to treat depression, anxiety disorders, Alzheimer’s and Parkinson’s disease, and other neurological disorders. They are also a factor protecting neurons from degeneration. Therefore, as you can see, neuronal cAMP is of great importance and a wide spectrum of properties that should be used.

Another, less known than an artichoke PDE-4 inhibitor is the African plant Sceletium Tortuosum, also known under the common name of Kanna or under the Zembrin patent. The component responsible for raising cAMP is the mesenbronon. Even Zembrin can sensibly support the clarity of thinking, and combining it with Forskolin gives a very efficient duo. We also receive a wider package of actions than in the case of artichoke. Kanna also has the ability to inhibit the serotonin transporter, and therefore acts as SSRIs. The difference is that you do not have to wait weeks for a therapeutic effect, because a positive action can be felt from the first dose. Another, slightly weaker mechanism of action of this unusual plant is the impact on the VAMT2 transporter, which facilitates the transport of neurotransmitters from presynaptic neurons to the synaptic cleft. Kanna reduces the responsiveness of the amygdala in response to stress, which means that we can work under time pressure when the deadlines are chasing us or other stressful factors surround us. Not only that, we can work efficiently then.



In conclusion, Forskolin significantly gains in efficiency in terms of the effect on the nervous system when we supplement it with a PDE-4 inhibitory supplement. The combination of these two classes of agents provides a greater increase in cAMP, because it’s stimulated on both sides – at the same time, the synthesis is increased and its metabolism is inhibited.

A popular and economical procedure is to add an artichoke extract, which is worth starting with. More demanding users may consider purchasing Sceletium Tortuosum extract, which extends the spectrum of action to improve well-being, better resistance to stress and even more efficient cognitive functions.

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