- Fun Fact Friday -

Hi all,

I hope you've had a great week and are glad that it's Friday.
Here's your Fun Fact Friday to end the week with some extra pizazz. Enjoy!

Please leave a review here if you enjoy reading this newsletter.

Question of the week

Q: Hi Hans, I would like to resolve a doubt but the NMDA is something to improve (increase) or No? On the one hand you say that the DHT increases and on the other you say that it is something to decrease so I would like to know what do you use to increase (or decrease) it? - Giuseppe

A: The NMDA receptor actually consists of a few complexes.

Functional NMDAR, a tetrameric protein complex, comprises of two subunits of a constitutive glycine binding NR1 and remaining two of glutamate binding NR2 from amongst NR2A, NR2B, NR2C, and NR2D subunits. Importantly, combination of different NR2 subunits is suggested to confer unique electrophysiological properties to this neurotransmitter receptor []. For example, alterations in the ratio of NR2A versus NR2B of NMDAR have been found to be associated with the changes in long term potentiation (LTP) and long term depression (LDP) functions during hippocampal plasticity involved in memory consolidation []. In addition, NR2A dominating combination of NMDAR is demonstrated to provide neuroprotection but NR2B rich NMDAR is known to drive the postsynaptic neuron towards apoptosis during glutamate excitotoxicity" (R)

"NR2A is known to impart neuroprotection and that of NR2B induces neuronal death during NMDAR activation. Neuronal nitric oxide synthase- (nNOS-) apoptosis pathway is known to mediate NMDAR led excitotoxicity. Excess NR2B is consistent with significantly enhanced nNOS expression, nitric oxide level." (R)

"alterations in the ratio of NR2A versus NR2B of NMDAR have been found to be associated with the changes in long term potentiation (LTP) and long term depression (LDP) functions during hippocampal plasticity involved in memory consolidation []. In addition, NR2A dominating combination of NMDAR is demonstrated to provide neuroprotection but NR2B rich NMDAR is known to drive the postsynaptic neuron towards apoptosis during glutamate excitotoxicity []. Thus, regulating NMDAR function by altering its composition, without pharmacological blockage of the channel, could be a unique and novel cerebral mechanism to prevent NMDAR overactivation led neurological disorders." (R)

We need NMDA receptor signaling. It plays an integral role in synaptic plasticity, which is a neuronal mechanism believed to be the basis of memory formation. It is particularly important because it is integral in the processes of long-term potentiation, synaptic plasticity, and memory formation.

The problem is, it either becomes dysfunctional, or glutamate levels are in excess, and thus blocking it with zinc and magnesium for example is therapeutic in those circumstances.

Bacopa, which is neuroprotective, lowers NR2B and increases NR2A (R).
Panax notoginseng inhibits NMDA with selectivity to NR2B (R).

Inhibition of NMDA can have great neuroprotective effects, but it's needed for focus and memory formation. In that case, DHT can help with focus and memory formation. 

This study shows that exercise-induced increase in DHT promotes hippocampal neurogenesis through NMDA receptor activation (R).
"These results support the hypothesis that, in male animals, mild exercise enhances hippocampal synthesis of dihydrotestosterone and increases AHN [hippocampal neurogenesis] via androgenenic mediation."

Another great study on the effects of DHT and neuroplasticity.
"Thus, androgen depletion impaired the synaptic plasticity in the hippocampus of SAMP8 and accelerated the development of Alzheimer's disease (AD)‑like neuropathology, suggesting that a similar mechanism may underlie the increased risk for AD in men with low testosterone. In addition, DHT regulated synaptic plasticity in the hippocampus of mild cognitive impairment (MCI) SAMP8 mice and delayed the progression of disease to Alzheimer's dementia. In conclusion, androgen‑based hormone therapy is a potentially useful strategy for preventing the progression of MCI in aging men. Androgens enhance synaptic markers (SYN, PSD95, and Drebrin), activate CREB, modulate the fundamental biology of synaptic structure, and lead to the structural changes of plasticity in the hippocampus, all of which result in improved cognitive function."

DHT, but not testosterone treatment,  reduces the expression of GluN2B (NR2B) in low BDNF animals, which shows that it can have neuroprotective properties (R).

And also:
"Therefore, the DHT-induced decrease in synapsin-1 and pGluN2B levels in the dorsal horn may contribute to the analgesic effect of this neuroactive steroid." (R)

But it's not as simple as NR2A is good an NR2B is bad. For example:
"Involvement of NMDA receptors containing GluN2B subunits in the pathophysiology of depression is rather complex. On the one hand tri-heterotrimeric NMDA receptors GluN1/2A/2B are probably necessary for the mobilization of synaptic protein (for example PSD-95, GKAP) during synaptic sprouting but, on the other hand extrasynaptic di-heteromeric GluN2B NMDA receptors conjugated with PSD-95 have a crucial role in the process of neuronal death"

"Sterlemann et al. (2010) for example showed that 7 wk of a social stress paradigm induces an increase in hippocampal GluN2B mRNA and protein levels in stressed mice (Sterlemann et al., 2010). Alternatively, in the study by Quan et al. (2011) 21 d of chronic unpredictable stress (CUS) induce a reduction in the expression of GluN2B receptor in PFC of stressed rats (Quan et al., 2011). Furthermore human post-mortem data indicate that the level of both subunits (GluN2A, GluN2B) is reduced in the prefrontal cortex and that GluN2A is elevated in amygdala in depressed patients (Feyissa et al., 2009; Karolewicz et al., 2009). Thus, generally, the level of glutamate NMDA receptor subunits in the brains of animals under stressful conditions is different than that found in depressed humans, which may indicate different mechanisms involved in the response to different stress procedures and the pathophysiology of depression." (R)

Low magnesium intake is linked to reduced amygdala-hypothalamic protein levels of GluN1-containing NMDA complexes which leads to dysfunctional GluN1 and 2 complexes (R). Supplementing magnesium can help to undo this and have cognitive-enhancing effects.


Fun fact 1
Someone that exercises correctly for 10 minutes can get better health and physique results than someone who slaves away for 1 hour with cardio or incorrect training. In my next vid, I'll be giving a few workout ideas of just 2-3 exercises you can do for great hormonal release that will only take you 5-10 min per workout.

Fun fact 2
Inosine has been shown to restore gut integrity (reverse leaky gut) by restoring ATP levels of the intestine (R). This is perfectly in line with the animal study that shows that niacinamide was able to restore intestinal function, by restoring NAD and ATP levels.
The human equivalent doses were 5-6g of inosine per day.
If you just combine it with a quinone or two, such as thymoquinone and beta-lapachone, you should be on your way to a happy gut.

500mg niacinamide
3g inosine x2 daily
2g Nigella sativa
500mg Pau d'arco

Fun fact 3
Ornithine has been shown to help with circadian rhythm entrainment and the dose was just 400mg (R). Ornithine has also been shown to lower excess cortisol and ammonia, which should help you sleep better and have better, cleaner energy.

Compound I find interesting
It's extracted from barley and is commonly used as a nootropic, exercise performance enhances and fat burner. I came across this compound when I was research herbs that can lower prolactin. The main herb is called Fructus Hordei Germinatus, which is quite effective at lowering prolactin by inhibiting MAPK. It's also a D2 agonist (while increasing D2 expression; so no desensitization) and MAO-B inhibitor, making it quite an effective pro-dopamine supplement.
Furthermore, it's been shown to inhibit pyruvate dehydrogenase kinase 3, which is an inhibitor of pyruvate dehydrogenase, the rate-limited step in glucose oxidation (R).

So all in all, it can be very effective at increasing energy, by promoting glucose oxidation and increasing dopamine and noradrenaline. The only downside is that the effects appear to be short-lived as it has a short half-life.

One superfood in my diet

2 giant fresh oysters straight from the ocean each day (the company harvests it in the morning and delivers it in the afternoon).
Although I don't believe in superfoods, oysters are definitely a great food.

Here are just a few of its great benefits:
"In addition, it is well known that oyster meat is a high-quality marine food resource that contains several vitamins and minerals [2]. Numerous studies have reported that oysters and their bioactive peptides have pharmacological benefits including anti-oxidant [3], anti-microbial [4], osteogenic [5,6], anti-inflammatory [7], postprandial blood glucose control [8], and anti-coagulant properties [1]." (R)

Oysters have been shown to enhance swimming performance in mice:
"The effects of oyster components on the swimming endurance of mice may be attributed to the high ratio of the branched-chain amino acid composition, bioactivity of taurine, and glycogen." (R)

Oysters meat also contains various peptides (similar to gelatin), which has added benefit to individual amino acids alone (R).
For example, two peptides include proline-valine-methionine-glycine-aspartic acid (PVMGA) and glutamine-histidine-glycine-valine (QHGV), which exhibited high antioxidative actions (R).

The main reason I'm having it in my diet is for the zinc, copper, selenium and iron. Being on a high milk diet increases the requirements of zinc, copper and iron (and manganese; but that's why I eat mussels). Oysters are also rich in taurine, aspartic acid, lysine, glutamic acid, glycine and alanine.

A new food/fruit I tried out recently
Dragon fruit.
My wife and I have made it a goal to try out something new at least once a month, whether it be food, a new area of exploration, new beer, or whatever the case may be. So if you have any suggestions for us feel free to shoot me an email and if we do get to try some of the suggestions out (or haven't tried it yet) I'll show what we tried and mention the first name of the person who made the suggestion for us. :)
To be honest, the Dragon fruit tasted a bit odd, not sure how to describe it. It definitely sounds and looks better than it tastes lol, but it could just have been the batch we got. I expected more sweetness. You can read my short post on Instagram if you want to find out what a few benefits are of the Dragon fruit.

Thanks to Zach for making the suggestion of adding a few images into my newsletter. If you have any suggestions for me to make my newsletter even better for you as my readers, please feel free to send me an email.

New article & video released this week If you enjoy reading my articles and find them informative, please don't forget to share this content with others so that they can benefit from the information as well.



That's it for today. Hope you all have a great weekend!

- Hansius

P.S. If you would like to give me some feedback e.g. what did you found interesting, or give any suggestions, maybe of things that you think I might find interesting; let me know by replying to this email.

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