Vitamin K+A may treat Alzheimer Disease (AD)
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Another very interesting study below, though I disagreed with some of its findings. Namely, the study discovered that by fusing the vitamin K2 (MK-4, also known as menaquinone-4 / menatetrenone) molecule with vitamin A (retinoic acid) they could reverse the AD pathology in a rodent model. The study spends a lot of time describing the already known role in K2 (M-4) in brain health and especially preventing (even treating?) dementias such as AD. However, it claims that K2 by itself has limited uptake into the brain and thus is not strong enough to exert a sufficient therapeutic effect needed to reverse AD. That is why the study fused the K2 molecule with retinoic acid and found that this conjugate has higher brain uptake and stronger effects on reversing both plaque accumulation and the mental deficits seen in AD. In other words, the study admits that it is K2 (MK-4) that is the main beneficial agent here, and that their newly synthesized compounds NovelK are simply acting as pro-dugs for K2 (MK-4), which suggests that using just K2 (MK-4) simply needs to reach higher concentrations to do its magic. My disagreement is that K2 (MK-4) has been found to have a dose-dependent accumulation in the brain, and the desired brain concentrations of the vitamin can be achieved with higher oral doses, or lower doses but administered topically. Given the laughable RDA for vitamin K, which is on the order of micrograms (mcg) it is little wonder that studies consider pharmacological doses to be on the order of a few milligrams (mg). As such, most in-vivo studies with vitamin K2 (MK-4) are handicapped by design and it is little surprise that they do not produce the amount of benefit desired by medicine in order to declare K2 to be a viable treatment for AD. In comparison, the human doses for reversing osteoporosis in Asian countries (especially Japan) are either 45mg daily, or even as high as 1mg/kg daily. To my knowledge, no such high doses (their animal equivalent) have been tried in AD models, and if they were tried we would have seen the same benefits as the one seen in this study. So, no need to wait for an expensive and patented K2+A conjugate to be patented and sold to the public as an AD drugs. Good ol’ vitamin K2 (MK-4) widely available from many vendors may be just as good and only at a fraction of the cost.
https://doi.org/10.1021/acschemneuro.5c00111
https://scitechdaily.com/breakthrough-vitamin-k-compounds-may-reverse-alzheimers-damage/
“…Neurodegenerative disorders such as Alzheimer’s, Parkinson’s, and Huntington’s disease occur when neurons in the brain gradually deteriorate and die. This progressive loss of nerve cells leads to symptoms like memory loss, cognitive decline, and difficulty with movement. Over time, these conditions severely impact quality of life and often leave patients dependent on constant care. While current medications can ease symptoms, they do not stop or reverse the disease, highlighting the urgent need for new treatment strategies. One promising direction focuses on encouraging the brain to generate new neurons through a process known as neuronal differentiation, which could replace damaged cells and potentially slow or reverse degeneration. Vitamin K, a fat-soluble nutrient best known for its role in blood clotting and bone health, has recently been linked to brain protection and neuron formation. However, naturally occurring vitamin K compounds such as menaquinone 4 (MK-4) may not be strong enough to serve as effective therapies for neurodegenerative diseases.”
“…Explaining the findings, Dr. Hirota stated, “The newly synthesized vitamin K analogues demonstrated approximately threefold greater potency in inducing the differentiation of neural progenitor cells into neurons compared to natural vitamin K. Since neuronal loss is a hallmark of neurodegenerative diseases such as Alzheimer’s disease, these analogues may serve as regenerative agents that help replenish lost neurons and restore brain function.””
“…To improve the potency of vitamin K, the researchers synthesized 12 vitamin K hybrid homologs conjugated with retinoic acid—an active metabolite of vitamin A known to promote neuronal differentiation, a carboxylic acid moiety, or a methyl ester side chain and compared the neuronal differentiation-inducing activity of the hybrid homologs.”
“…The team then performed computer-based structural modeling and molecular docking experiments to determine whether vitamin K analogs interact directly with mGluR1. The results confirmed a strong binding relationship between the Novel VK compound and mGluR1, suggesting an enhanced biological effect. The researchers next examined how well Novel VK was absorbed by cells and converted into its active form, MK-4, both in cell cultures and in mice. They observed that MK-4 levels inside cells rose in proportion to the concentration of Novel VK, and that the new compound converted into MK-4 more efficiently than natural vitamin K. Animal testing further demonstrated that Novel VK maintained a stable pharmacokinetic profile, successfully crossed the blood-brain barrier, and produced higher levels of MK-4 in the brain than the standard form of vitamin K.”