Posts made by haidut

Only posting this as a good indicator of the steadily deteriorating environmental conditions we are all facing. It is already well-established that rates of cancer, CVD, diabetes and neurodegenerative conditions is rising quickly in the youngest segment of the global population, but the article below gives a good idea into just how widespread and impactful the deterioration of health has been over the last few decades. I hope more people see this article and realize that the global population is under attack and fighting for its very survival, regardless of what mainstream media would have us believe. Whether this attack is due to idiocy or malign intent on behalf of the powers that be, I leave it to my readers to decide for themselves.

https://www.thelancet.com/gbd

https://studyfinds.org/3-billion-neurological-disorders/

“…A damning new study reveals that nearly half of the global population suffers from neurological disorders. A team of international researchers have unveiled a significant increase in both the prevalence and the health impact of neurological conditions, including incidents of stroke, Alzheimer’s disease, and meningitis, over the past 30 years. This research supports the World Health Organization’s Intersectoral Global Action Plan on epilepsy and other neurological disorders, aiming to reduce the impact and improve the quality of life for affected individuals and their families.”

Via: http://haidut.me/?p=2649

A good summary article on the multitude of mechanisms through which vitamin D acts to target virtually all pathways known to be involved in aging. One mechanisms I did not see mentioned is that vitamin D is a known inducer/activator of the anti-aging Klotho gene, so I am adding a reference on that too (first link below). Considering that vitamin D is a potent metabolic enhancer, as well as stimulant of mitochondrial biogenesis, the lifespan extending effects are not really surprising, but it is nice to see a high-level breakdown of all the pathways through which vitamin D may work in the human body.

https://pubmed.ncbi.nlm.nih.gov/21982773/

https://doi.org/10.3390/nu16060906

https://www.news-medical.net/news/20240326/Vitamin-D-shows-promise-in-targeting-agings-biological-mechanisms-study-finds.aspx

“…VitD regulates protein homeostasis, impacting longevity and muscle health. In C. elegans, VitD reduces protein insolubility and toxicity, promoting longevity. In rats, VitD deficiency increases muscle protein breakdown and contributes to muscle atrophy. VitD also influences cellular signaling involved in myogenesis and activates adenosine monophosphate-activated protein kinase (AMPK) during metabolic stress. VitD impacts cellular and mitochondrial function across various systems. It reduces oxidative stress, improves muscle and lung function, and attenuates oxidative damage in neurodegenerative and cardiovascular diseases. VitD also shows potential in mitigating mitochondrial dysfunction in conditions like sarcopenia and Crohn’s disease. VitD also plays a crucial role in regulating immune responses by its widespread distribution among immune cells and autonomic control of active VitD concentration at inflamed sites. While some studies link VitD supplementation to reduced inflammation markers in various conditions, overall evidence is inconclusive despite potential benefits in certain diseases. Chronic inflammation can disrupt gut microbiota balance, as seen in conditions like human immunodeficiency virus (HIV) infection and osteoarthritis (OA). VitD supplementation shows promise in restoring microbial balance and reducing inflammation. Studies indicate VitD’s role in enhancing antimicrobial peptides, stabilizing gut barriers, and regulating microbiota composition. VitD shows potential in bone regeneration and neural stem cell modulation, crucial for nervous system development and repair. It influences signaling in brain neurogenesis and may have therapeutic implications in conditions like acute myeloid leukemia. However, further research is needed to explore its full potential in stem cell therapy…Understanding aging involves complex interactions among various biological mechanisms. VitD shows promise in influencing the hallmarks of aging, including genomic stability and senescence.”

Via: http://haidut.me/?p=2647

Once again, the false equivalence between bioidentical progesterone and synthetic progestins (which medicine has been promoting for decades) is on full display. The study below found that chronic use of several of the most commonly prescribed synthetic progestins increases risk of developing intracranial meningioma. That tumor is rare and usually does not cause serious issues when forming in the spinal column/cord area. However it can become dangerous and even life threatening when forming inside the head, and that type is exactly what the study found elevated risk for from the use of the synthetic progestins. On the flip side, several studies have demonstrated reduced risk of meningioma when using biodentical progesterone. The findings of the study are likely explainable by the fact that estrogen is a known cause/promoter of meningiomas and many/most synthetic progestins are actually estrogenic (as I posted about years ago). In contrast, bioidentical progesterone has purely anti-estrogenic effects by being both an estrogen receptor antagonist as well as an aromatase inhibitor.

https://www.bmj.com/content/384/bmj-2023-078078

https://www.healthday.com/healthpro-news/neurology/prolonged-use-of-progestogens-may-raise-risk-for-intracranial-meningioma

“…Noémie Roland, M.D., M.P.H., from the EPI-PHARE Scientific Interest Group in Saint-Denis, France, and colleagues conducted a national case-control study involving 108,366 women overall to examine the risk for intracranial meningioma associated with use of selected progestogens. Cases included 18,061 women living in France who had intracranial surgery for meningioma between Jan. 1, 2009, and Dec. 31, 2018; each case was matched to five controls (90,305 controls). The researchers found that the risk for meningioma was increased with use of medrogestone (0.2 percent among cases versus 0.1 percent among controls; odds ratio, 3.49), medroxyprogesterone acetate (injectable; 0.05 versus 0.01 percent; odds ratio 5.55), and promegestone (0.5 versus 0.2 percent; odds ratio, 2.39). The excess risk was driven by use for one year or longer. No excess risk for intracranial meningioma was seen for progesterone, dydrogesterone, or levonorgestrel intrauterine systems. Due to the small number of people receiving dienogest or hydroxyprogesterone, no conclusions could be drawn.”

Via: http://haidut.me/?p=2645

Another study that will probably make me plenty of new enemies among the anti-retinol crowd. I am posting it here because one of the main claims of the anti-retinol groups is that dietary restriction of vitamin A not only has no negative effects on health, but is actually highly beneficial. Well, it seems that when it comes to brain health at least, the opposite is true. It took only 12 weeks of vitamin A restriction to establish AD pathology, while the same amount of time supplementing vitamin A was sufficient to produce strong beneficial effects. Crucially, vitamin A restriction elevated biomarkers of gut permeability (D-lactate and DAO), which matches with the post I just did on endotoxin/LPS being a major causative factor in AD. Conversely, vitamin  A supplementation was effective at restoring the gut barrier, and subsequently preserving cognition even in animals with already established AD.

https://www.frontiersin.org/articles/10.3389/fnut.2024.1367086/full

https://www.news-medical.net/news/20240328/Dietary-vitamin-A-shows-promise-in-Alzheimers-disease-intervention-study-finds.aspx

“…In the present study, researchers investigated the effects of dietary vitamin A on the intestinal transcriptome, inflammation, gut microbiota, and amyloid-β (Aβ) pathology. Thirty APP/PS1 mice (AD mouse model) were randomly assigned to three groups based on body weight. Mice received a diet with deficient (VAD), normal (VAN), or enriched (VAS) levels of vitamin A. Body weight and food intake were recorded every week.”

“…Mice in the VAN group could directly locate the platform and move to its position even when removed. These mice took less time to find the platform than other groups. Moreover, the VAS group took less time than the VAD group. There were no significant differences in the time spent finding the platform between VAS and VAN groups. When the platform was removed, the VAN group repeatedly crossed the platform area. Mice in the VAD group showed significantly greater Aβ deposition in the brain than in other groups. The VAS group also had higher Aβ deposition than the VAN group, albeit not statistically significant. The Shannon index was higher in the VAS and VAN groups than in the VAD group; however, it was similar between the VAS and VAN groups. VAN and VAS groups had greater microbial diversity than the VAD group. Overall, 571 genes with differential expression were identified between the VAS and VAD groups. Between VAN and VAD groups, 313 differentially expressed genes were identified. Further, there were 243 genes with differential expression between VAN and VAS groups. DAO and D-lactate levels were significantly elevated in the VAD group compared to the VAS and VAN groups. Mice in the VAD group exhibited more significant levels of inflammatory cytokines than other groups.

“…In sum, the study showed that a 12-week VAD diet reduced serum levels of retinol, impaired cognition, and increased Aβ pathology in mice. On the contrary, a diet enriched with vitamin A increased retinol, reduced Aβ, and preserved cognition. Overall, the findings highlight the significance of vitamin A in AD pathology and behavior.”

Via: http://haidut.me/?p=2643

Nothing surprising here to my readers, but I try to post about such studies since they are usually a marker of an upcoming major shift in medical dogmas. Considering 99%+ of all AD clinical trials over the last 2+ decades have abysmally failed, new ideas about this conditions are urgently needed. The study below is a good summary of the ideas and findings of many other studies, most of which I have posted about on this blog. Namely, endotoxin/LPS is perhaps the major cause of AD, as well as virtually all other neurodegenerative conditions.

https://molecularneurodegeneration.biomedcentral.com/articles/10.1186/s13024-024-00722-y

“…Lipopolysaccharide (LPS) constitutes much of the surface of Gram-negative bacteria, and if LPS enters the human body or brain can induce inflammation and act as an endotoxin. We outline the hypothesis here that LPS may contribute to the pathophysiology of Alzheimer’s disease (AD) via peripheral infections or gut dysfunction elevating LPS levels in blood and brain, which promotes: amyloid pathology, tau pathology and microglial activation, contributing to the neurodegeneration of AD. The evidence supporting this hypothesis includes: i) blood and brain levels of LPS are elevated in AD patients, ii) AD risk factors increase LPS levels or response, iii) LPS induces Aβ expression, aggregation, inflammation and neurotoxicity, iv) LPS induces TAU phosphorylation, aggregation and spreading, v) LPS induces microglial priming, activation and neurotoxicity, and vi) blood LPS induces loss of synapses, neurons and memory in AD mouse models, and cognitive dysfunction in humans. However, to test the hypothesis, it is necessary to test whether reducing blood LPS reduces AD risk or progression. If the LPS endotoxin hypothesis is correct, then treatments might include: reducing infections, changing gut microbiome, reducing leaky gut, decreasing blood LPS, or blocking LPS response.”

Via: http://haidut.me/?p=2641

The role of vitamin D in auto-immune conditions and especially MS has been studied for decades. It is a proven epidemiological fact that MS rates steadily increase with latitude (low sunlight exposure) and are virtually nil in people living in tropical or equatorial areas of the globe. Despite this proven relationship, medicine refuses to consider vitamin D as a prophylactic or treatment intervention for MS. The study below demonstrated that a relatively low, human-equivalent dose of 20,000 IU – 25,000 IU of vitamin D3 once weekly for just 6-7 weeks was able to not only ameliorate the symptoms of advanced MS, but it actually showed a trend towards a reversal of the condition.

https://pubmed.ncbi.nlm.nih.gov/37571246/

https://nutraceuticalbusinessreview.com/vitamin-D-multiple-sclerosis-late-stage

“…Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) that affects around 13,500 people in Austria. Due to the different ways it progresses and its variety of symptoms, the “disease with a thousand faces” is difficult to research and treat. In a study conducted by the neuroimmunology research team at the Department of Neurology, Michaela Tanja Haindl has investigated in a laboratory model how vitamin D has an effect in late-stage multiple sclerosis and what consequences this may have for MS research in general.”

“…It was demonstrated that significantly more cellular structures were preserved in this part of the brain in rats given vitamin D in addition to their normal diet. Not only were myelin and nerve cells better preserved, but there was also a reduction in apoptotic cells and microglial activation. Animals given vitamin D had significantly fewer serum neurofilament light chains (sNfL). These filaments are currently regarded as a predictor of nerve cell damage and thus a biomarker for the progression/severity of multiple sclerosis. In addition, the vitamin displayed an antioxidant effect in test animals, which was also detected in the blood serum. Rats treated with vitamin D had not only significantly more protective polyphenols in their blood, but a higher total antioxidative capacity (TAC) as well. Since oxidative stress is considered to possibly trigger and intensify MS, this positive effect of the “sunshine vitamin” might be substantiated by further research.”

Via: http://haidut.me/?p=2639

Actual title of the article, quoting the main author of the Nature op-ed. There has been a steady stream of recent studies challenging that depression is due to “faulty genes”, and even less so due to low serotonin in the brain. If anything, the available evidence so far strongly implicates high serotonin as the cause and not the cure for depression. More importantly, this most recent publication shines the light directly on environmental/social causes (e.g. chronic stress, financial insecurity/poverty, meaningless lives, etc) of depression and makes a strong case that it is those causes that need to be “treated”, not the brain itself as the brain seems to be functioning perfectly well in depressed people. Such position/opinion is anathema to both Big Pharma and public health policy, which have spent billions to shift the blame away from the crushing environment we all live in, caused by deliberate political decisions spanning decades. In other words – there is no depression as an organic disease, it is just a normal response to the drastically low quality of life we all have been experiencing for decades, and which continue to deteriorate daily. So, the solution is (and has always been) political, not pharmacological. I sense that a revolution is brewing and we may witness it play out globally in the coming months/years.

https://www.nature.com/articles/s41380-024-02462-3

Researchers: Depression Is “A Normal Brain Responding to Stress or Adversity”

“…“Difficult lives explain depression better than broken brains,” according to researchers in a recent letter to the editor in Molecular Psychiatry. The authors, led by Joanna Moncrieff, argue that there is no real evidence for brain differences in depression but that there is convincing evidence of the role of social and environmental factors as a cause. “We suggest that in the absence of convincing proof of a pathological process, it is more likely that depression is part of the range of emotional reactions to the circumstances of life that are typical of humans,” write Moncrieff et al. “We agree that mental activity arises from brain activity, but it seems more likely that depression is the result not of a faulty brain but rather a normal brain responding to stress or adversity: in other words, a behavioral state best understood at the level of the mind (that is, the thoughts, feelings, and actions of human beings in their social context) and not of the brain,” they add.”

Via: http://haidut.me/?p=2637

The role of endotoxin/LPS in chronic liver disease and failure is well-known in animal research. LPS is one of the most commonly used methods for quickly inducing liver inflammation, fattening, scarring/cirrhosis, and ultimately failure. However, the role of LPS in human liver disease continues to be denied by medicine with the claim that in healthy people LPS is so quickly neutralized by the liver that it does not have much chance to cause damage. Yet, multiple human studies have demonstrated that alcohol – a universally recognized factor in liver disease – can only cause damage in animals/humans with intact microbiome. It does not cause liver disease in organisms with sterile guts, or organisms where the gut barrier (which alcohol readily compromises) has been restored with things such as dietary saturated fat, serotonin (especially 5-HT3) antagonists, NAD+ precursors such as niacinamide, TLR4 (endotoxin receptor) blockers, etc. Thus, the evidence that endotoxin/LPS is perhaps the main cause of liver disease is overwhelming. As such, measures to reduce endotoxin levels directly should be prophylactic and therapeutic for liver disease. And that is exactly what the study below states. It found that the oral administration of “…tiny…carbon beads” (a fancy, expensive and non-superior analog of activated charcoal) reduced LPS levels and blocked liver scarring (cirrhosis), with no side effects (already confirmed in humans).

https://doi.org/10.1136/gutjnl-2023-330699

Carbon Beads Aid in Restoring Healthy Gut Microbiome and Reducing Liver Disease Progression

“…The study, published in Gut, found that the carbon beads, licensed to UCL-spinout Yaqrit, were effective in restoring gut health and had a positive impact on liver, kidney and brain function in rats and mice. They were also found to be safe for human use. The next step will be to see if the same benefits can be realised in humans, which would pave the way for them to be used to treat diseases linked to poor gut health.”

“…Explaining the current clinical challenges, senior author Professor Rajiv Jalan from the UCL Institute for Liver and Digestive Health, said: “The influence of the gut microbiome on health is only just beginning to be fully appreciated. When the balance of the microbiome is upset, ‘bad’ bacteria can proliferate and out-compete the ‘good’ bacteria that keeps the gut healthy. “One of the ways they do this is by excreting endotoxin, toxic metabolites and cytokines that transform the gut environment to make it more favourable to them and hostile to good bacteria. These substances, particularly endotoxin, can trigger gut inflammation and increase the leakiness of the gut wall, resulting in damage to other organs such as the liver, kidneys and brain. “In cirrhosis, a condition characterised by scarring of the liver, it is known that inflammation caused by endotoxins can exacerbate liver damage. Part of the standard treatment for cirrhosis is antibiotics aimed at controlling bad bacteria, but this comes with the risk of antibiotic resistance and is only used in late-stage disease.” To overcome this, scientists at UCL, in collaboration with Yaqrit, developed tiny oral carbon beads, that have a special microscopic physical structure designed to adsorb both large and small molecules in the gut.”

“…They found that when ingested every day for several weeks, the beads were effective in preventing the progress of liver scarring and injury in animals with cirrhosis, and reduced mortality in animals with acute-on-chronic-liver-failure (ACLF). The beads were also tested on 28 cirrhosis patients and proved to be safe with negligible side effects. If the same benefits observed in animal models occur in humans, the beads could be an important new tool to help tackle liver disease. Michal Kowalski, a Vice President and the CARBALIVE product lead at Yaqrit, said: “These novel, engineered carbon beads, which are swallowed and pass through the body unaltered, are smaller than a grain of salt. They work by absorbing the endotoxins and other metabolites produced by ‘bad’ bacteria in the gut, creating a better environment for the good bacteria to flourish and helping to restore microbiome health. This prevents these toxins from leaching into other areas of the body and causing damage, as they do in cirrhosis. “The results in animal models are very positive, with reduction in gut permeability, liver injury, as well as brain and kidney dysfunction.”

Via: http://haidut.me/?p=2632

It is hard to accept that something as ubiquitous as LPS may have such profound effects on our social behavior, but the findings are the latest in a very long line of research demonstrating that chronic inflammation (which LPS is “great” at inducing) result in social withdrawal and lack of empathy on behalf of the individual experiencing chronic inflammation. Since LPS is derived almost entirely from bacteria in the gut, and this process is controlled almost entirely by diet, the findings of the study suggest once again that “we are what we eat”, at least when it comes to personality and (social) behavior. Thus, one should take great care to avoid consumption of LPS-inducing diets, such as the ones containing high-fat/low-carb, resistant starch, PUFA, food additives that cause gut irritation, excessive alcohol consumption, etc. Even in the presence of such LPS-inducing diets, it may be feasible to mitigate the negative effects of such diets by simply administering OTC anti-inflammatory/anti-endotoxin substances such as charcoal, niacinamide, aspirin, vitamin D, glycine/gelatin, and insoluble-fiber-rich foods such as carrots, turnips, parsnip, rutabagas, etc.

https://dx.doi.org/10.1016/j.bbi.2024.03.032

https://medicalxpress.com/news/2024-05-infections-social-empathy.html

“…Experimentally, the various facets of sickness behavior can be induced by the administration of bacterial endotoxin, in short LPS for lipopolysaccharide. The researchers from Bochum and Essen made use of this mechanism. They administered a low dose of LPS or—as a placebo—an injection with physiological saline to 52 voluntary female participants. The women were then asked to rate various social interactions. They were shown pictures of women who were either in somatic or psychological pain or in an emotionally neutral interaction with a male counterpart. “The results surprised us,” explains first author Vera Flasbeck from the LWL-University Hospital Bochum. “While the empathy for somatic pain was largely the same in the LPS and placebo group, there was a significant reduction in empathy for psychological pain in the test subjects exposed to LPS.” In the study, acute inflammation thus led to a reduction in people’s empathy for the psychological pain of others.”

“…”We assume that the reduced empathy serves to save energy in terms of social engagement in periods of illness,” explains Prof. Dr. Martin Brüne from the LWL-University Hospital Bochum, who supervised the study together with Professors Manfred Schedlowski and Harald Engler from the Institute of Medical Psychology and Behavioral Immunobiology at the Faculty of Medicine of the University of Duisburg-Essen. “The results of the study indicate that inflammation—as in the case of physical infections, for instance—affects both our physical health and our interpersonal relationships.”

Via: http://haidut.me/?p=2629

The connection between chronic stress and schizophrenia is well-established but medicine continues to vehemently deny that stress on its own can cause psychotic states such as schizophrenia. To this day, the most commonly used drugs for schizophrenia are so-called dopamine antagonists, yet recent studies have demonstrated that they all have anti-serotonin effects as well. Serotonin is the primary central control mechanism behind cortisol production and anti-serotonin drugs have been successfully used to treat hyper-cortisol states such as Cushing disease/syndrome. Thus, it would be plausible to conclude that elevated cortisol is a causative factor in schizophrenia, likely downstream from elevated serotonin. On a side, but related note, this suggests that SSRI drugs at the very least exacerbate psychotic states such as schizophrenia, if not outright cause it. Yet, SSRI drugs are widely prescribed to patients with schizophrenia to “prevent” them from developing depression or “treat” already established one. Now, measuring cortisol levels in blood is tricky and more often than not patients with mental health conditions do not present with consistently elevated cortisol levels. However, even if cortisol levels are normal in serum, one can still be in a state of relative cortisol dominance. How so? Well, multiple human and animal studies have demonstrated that it is not absolute cortisol levels that matter most for health, but the ratio of cortisol to anti-cortisol steroids such as DHEA and testosterone. In fact, the serum cortisol/DHEA ratio has been consistently shown to be one of the most reliable biomarkers of all-cause mortality and morbidity, regardless of sex, age, health history, diet, genetics, etc. Thus, ideally one would want to not only measure cortisol, the cortisol/DHEA and the cortisol/testsoterone ratio, but do the measurement in a way that presents a long-term picture that can smooth out any outliers that often occur on single blood tests. Hair/nail steroid analysis is perfectly suited for such tasks, and the study below demonstrated that hair cortisol, cortisol/DHEA and cortisol/testosterone ratios are all strongly associated with schizophrenia severity, likely being causative factors for this condition.

https://doi.org/10.1016/j.psyneuen.2024.107049

“…Hair samples were taken from 137 SCZ patients and 73 controls. The SCZ patients were diagnosed by their attending physician according to the Diagnostic and Statistical Manual of Mental Disorders IV and were clinically stable after treatment. Gender, age, BMI, frequency of hair washing, marital status, education level, family history of mental illness and clozapine dosage were concurrently collected as covariates. The 10-item perceived stress scale (PSS-10) and the social readjustment rating scale were used to assess chronic stress status in SCZ patients. Eight hair biomarkers, cortisol, cortisone, dehydroepiandrosterone (DHEA), testosterone, progesterone, cortisol/cortisone, cortisol/DHEA and cortisol/testosterone, were measured by high performance liquid chromatography tandem mass spectrometer. Among them, cortisol, cortisone, DHEA and cortisol/DHEA reflected the functional activity of the HPA axis, and testosterone and progesterone reflected the functional activity of the HPG axis, and cortisol/cortisone reflected the activity of 11_β_-hydroxysteroid dehydrogenase types 2 (11_β_-HSD 2), and cortisol/testosterone reflected the HPA-HPG interaction. SCZ patients showed significantly higher cortisone and cortisol/testosterone than controls (p<0.001, η²_p=0.180 and p=0.015, η²__p=0.031),_ lower testosterone (p=0.009, η²__p=0.034), progesterone (p<0.001, η²__p=0.069) and cortisol/cortisone (p=0.001, _η²_p=0.054). There were significant intergroup differences in male and female progesterone (p=0.003, _η²_p=0.088 and _p=_0.030, _η²_p=0.049) and female testosterone (p=0.028, _η²_p=0.051). In SCZ patients, cortisol, cortisol/cortisone, cortisol/DHEA and cortisol/testosterone were positively associated with PSS-10 score (_p_s<0.05, 0.212<_r_s< 0.265).”

Via: http://haidut.me/?p=2627

Another win for vitamin K – one of the least studied, yet most versatile vitamins. While vitamin K is officially considered to have impact mostly on coagulation and bone health, its quinone-like structure/function suggests it may have benefits for every organ, especially high-energy-consuming ones like our brain (which consumed 20% of daily energy production). The study below demonstrated that vitamin K downregulates the expression of inflammatory mediators while also upregulating the activity of enzymes involved in preventing the accumulation of beta-amyloid plaques in the brain. Both of these pathways are thought to be the primary driving mechanisms in progressive, neurodegenerative and “incurable” conditions such as AD. Maybe all that is needed for brain health is a weekly serving of liver (a rich source of vitamin K) or a little supplementation with this gem of a vitamin.

https://doi.org/10.3390/cells13010058

https://www.nutritionaloutlook.com/view/new-study-shows-that-vitamin-k2-as-mk-7-may-have-neuroprotective-qualities

“…A recent study1 conducted by researchers at Sapienza University of Rome found that vitamin K2 as menaquinone-7 (MK-7) may have neuroprotective properties. In the study, researchers examined the effects of MK-7 and menaquinone-4 (MK-4) on neuroblastoma cells to understand how different forms of vitamin K2 impact the expression of genes involved in neurodegeneration and neuroinflammation. Results showed that MK-7 was associated with the “downregulation of neurodegeneration– (PSEN1 and BACE1) and neuroinflammation– (IL-1β and IL-6) associated genes.” Additionally, genes related to protective rolls toward amyloidogenesis – involved in the formation and growth of amyloid structures – were upregulated (ADAM10 and ADAM17). After profiling DNA methylation patterns of genes known to be epigenetically regulated, the researchers found that there was a correlation between hypermethylation and the downregulation of PSEN1, IL-1β and IL-6. According to the researchers, this suggests that Vitamin K may have neuroprotective qualities by mitigating neurodegenerative and neuroinflammatory pathways, which is mediated by the hypermethylation of the regulatory regions of PSEN1, IL-1β and IL-6.”

Via: http://haidut.me/?p=2625

Double whammy for two popular medical dogmas. One of them is that serotonin is the “happy hormone” and raising its levels has a variety of benefits, one of which is reducing anxiety. After all, it is hard to be happy if anxiety is through the roof, right? The second one is that low-carb/high-fat diets (also known as keto diets) are the best thing for health since the advent of antibiotics. Well, wrong on both counts, according to the study below. It found that a high-fat (45% of calories) diet caused anxiety by increasing serotonin production in the gut. It actually increased the expression of the enzyme tryptophan hydroxylase (TPH), which is even worse than simply increasing serotonin production directly since increased expression levels can persist for a long time and often do not decline back to baseline even if the offending (TPH-increasing) factor has been removed from the organism. The study actually refutes yet another medical dogma, which claims that gut-derived serotonin does not have central effects since it is unable to cross the blood-brain barrier. Considering the ubiquity of SSRI drugs, low-carb diets, and exhaustive exercise (which also boosts serotonin production) it is little wonder that anxiety rates are skyrocketing and it is now the most common mental health disorder.

https://biolres.biomedcentral.com/articles/10.1186/s40659-024-00505-1

https://www.colorado.edu/today/2024/06/13/how-high-fat-diet-could-make-you-anxious

“…When we’re stressed out, many of us turn to junk food for solace. But new CU Boulder research suggests this strategy may backfire. The study found that in animals, a high-fat diet disrupts resident gut bacteria, alters behavior and, through a complex pathway connecting the gut to the brain, influences brain chemicals in ways that fuel anxiety.”

“…When compared to the control group, the group eating a high-fat diet, not surprisingly, gained weight. But the animals also showed significantly less diversity of gut bacteria. Generally speaking, more bacterial diversity is associated with better health, Lowry explained. They also hosted far more of a category of bacteria called Firmicutes and less of a category called Bacteroidetes. A higher Firmicutes to Bacteroidetes ratio has been associated with the typical industrialized diet and with obesity. The high-fat diet group also showed higher expression of three genes (tph2, htr1a, and slc6a4) involved in production and signaling of the neurotransmitter serotonin—particularly in a region of the brainstem known as the dorsal raphe nucleus cDRD, which is associated with stress and anxiety. While serotonin is often billed as a “feel-good brain chemical,” Lowry notes that certain subsets of serotonin neurons can, when activated, prompt anxiety-like responses in animals. Notably, heightened expression of tph2, or tryptophan hydroxylase, in the cDRD has been associated with mood disorders and suicide risk in humans. “To think that just a high-fat diet could alter expression of these genes in the brain is extraordinary,” said Lowry. “The high-fat group essentially had the molecular signature of a high anxiety state in their brain.”

Via: http://haidut.me/?p=2623

Vitamin K is one of the least-studied vitamins, though that has been changing lately, largely due to the studies showing vitamin K is crucial for bone and cardiovascular health, leading to its approval in Asian countries as a pharma drug for treating osteoporosis. In addition, recent studies in Western countries have led to the FDA considering approving vitamin K as treatment for liver cancer as well as several other malignancies (especially hematological ones). Despite all those studies, the role of vitamin K in pulmonary health is virtually completely unexplored, probably due to the fact that the scientific establishment does not expect that a coagulation and bone controlling vitamin has anything to do with lung function. The study below demonstrates that vitamin K is indeed very important for lung health and low dietary levels can drive conditions such as chronic obstructive pulmonary disease (COPD), while raising dietary levels may wards off such diseases and maybe even treat them. One need only look at the vitamin K molecule to realize that is is a quinone, and as such is crucial for redox balance, OXPHOS, and systemic energy production. In addition, vitamin K has known anti-estrogenic effects and estrogen has a known causative and promoting role in pulmonary conditions such as COPD.

https://openres.ersjournals.com/content/early/2023/06/29/23120541.00208-2023

https://www.upi.com/Health_News/2023/08/10/vitamin-K-lungs-health/2591691672872/

“…It may not get the publicity of some better-known vitamins like D, but vitamin K — found in leafy green vegetables — may boost lung health. A new, large study — published Thursday in ERJ Open Research — suggests that people who have low levels of this vitamin also have less healthy lungs. They are more likely to report having asthma, chronic obstructive pulmonary disease (COPD) and wheezing. “Our results suggest that vitamin K could play a part in keeping our lungs healthy,” said researcher Dr. Torkil Jespersen of Copenhagen University Hospital and the University of Copenhagen in Denmark.”

Via: http://haidut.me/?p=2621

Not really surprising findings, considering the extensive published evidence showing NAD+ is crucial for immune system function, and that depletion of NAD+ can cause both immunodeficiency, as well as inflammatory “auto-immune” conditions, the latter of which are thought to  involved overactive immune system function targeting a specific organ or tissue.

http://dx.doi.org/10.1016/j.cell.2024.05.034

https://www.sciencedaily.com/releases/2024/06/240614155341.htm

“…Nucleotide-binding oligomerization domain-like receptors (NLRs) are a large family of important molecules involved in inflammatory signaling. They are generally thought to function as innate immune sensors that detect threats. However, the specific roles of several NLRs in sensing are not yet understood. Scientists at St. Jude conducted a large screen, testing a specific NLR, NLRC5, to see what threats activate it. Through their efforts, they discovered that depletion of nicotinamide adenine dinucleotide (NAD), a molecule essential in energy production, triggers NLRC5-mediated cell death through PANoptosis.”

“…Upon identifying the heme-containing PAMP, DAMP and cytokine combinations that trigger NLRC5-dependent inflammatory cell death, the researchers further investigated how NLRC5 is regulated. They found that NAD levels drive NLRC5 protein expression. If NAD is depleted, that sounds an alarm that there is a threat the immune system should recognize. The researchers found that depletion of NAD is sensed by NLRC5, triggering PANoptosis. “By supplementing with the NAD precursor, nicotinamide, we reduced NLRC5 protein expression and PANoptosis,” said co-first author Nagakannan Pandian, PhD, St. Jude Department of Immunology. “Therapeutically, nicotinamide has been widely studied as a nutrient supplement, and our findings suggest it could be helpful in treating inflammatory diseases.”

Via: http://haidut.me/?p=2619

Estrogen receptor positive (ER+) breast cancer is the most common type of cancer affecting women worldwide and accounts for more than 80% of all breast cancer diagnoses worldwide. It is also the most common breast cancer type in males, though males rarely get breast cancer. The standard of care therapy for such types of cancer is the administration of a an estrogen blocker such as tamoxifen or clomiphene, often in combination with an aromatase inhibitor (AI). However, the estrogen blockers are not true anti-estrogens and are in fact officially known as selective estrogen receptor modulators (SERM), since they have potent estrogenic effects in many tissues despite having (partially) anti-estrogenic effects in breast tissue. These SERM drugs are actually synthetic non-steroidal estrogens, which have been modified slightly to achieve their selective (and partial) estrogen blocking effects in some tissues. As a result of this cunning partial estrogenicity, the response to SERM therapy is an abysmally low ~30%, which can be raised to 50%-60% when combined with an AI drug. Interestingly enough, therapy by AI drug alone, especially with steroidal AI drugs such as exemestane, can be as high as 80%, which further corroborates the dangers of SERM drugs. However, SERMs remain first line of therapy for most women with ER+ breast cancer and are unlikely to be replaced any time soon. The study below reports the stunning findings that adding progesterone to tamoxifen therapy not only completely blocked tumor growth after just 4-5 weeks of treatment, but actually started to induce tumor regression in subsequent weeks. This finding is the exact opposite of current medical recommendations, which state that progesterone therapy should be avoided since it can both cause breast cancer de-novo and promote the growth of already established tumors. In fact, states such as California have mandatory warning label requirements on any product sold in California that contains progesterone. The real kicker to the study below is that progesterone was found to be therapeutic even in progesterone receptor positive (PR+) breast tumors – the very tumor type progesterone is supposed to cause/stimulate!

In terms of practical takeaways, the progesterone dose was not even that high. The human-equivalent doses was 0.6mg/kg daily, which means for most people 50mg-60mg progesterone daily should do the trick. When progesterone is dissolved in tocopherols and taken orally it has systemic bioavailability of about 60%-70%, which means a daily dose of about 100mg should be enough to replicate the study. While the study is politically correct and says that progesterone worked by enhancing the anti-estrogenic effects of tamoxifen, the real story is that progesterone simply blocked the partial estrogenic effects of tamoxifen. As such, an possibly optimal hormonal treatment of ER+ breast cancer may be a combination of a true anti-estrogen such as progesterone and a steroidal AI such as exemestane.

http://dx.doi.org/10.1038/nature14583

https://www.dailymail.co.uk/health/article-3153698/Breast-cancer-breakthrough-Hormone-Pill-shrinks-tumours-half-cases-say-scientists.html

“…In a landmark study, Cambridge University researchers have shown that progesterone – an inexpensive drug used in contraceptives – slows the growth of tumours. In lab tests, it made tamoxifen, the gold standard breast cancer medicine, work twice as well as usual. As a result, experts believe it could be a life-saver. The journal Nature said it was ‘time to rethink breast cancer’. Researcher Jason Carroll said: ‘The results are pretty clear and potentially have direct benefits for many women with breast cancer.’ Dr Carroll’s research centres on tumours that are fuelled by the hormone oestrogen. Some of these are also sensitive to progesterone, a hormone used in contraception. Dr Carroll, who is funded by Cancer Research UK, showed that…progesterone ‘talks’ to the oestrogen that is trying to feed the tumour. This stops the cancer from growing as quickly. In tests on mice with tumours, giving progesterone at the same time as tamoxifen, a drug widely used to stop breast cancer coming back after surgery, had a dramatic effect.“

Via: http://haidut.me/?p=2616

An actual human, randomized placebo-controlled trial. Daily in take of 1,000 nicotinamide riboside (NR) – which has been shown to be non-superior to niacinamide in terms of raising NAD+ levels – for 6 months improved endurance in people with peripheral vascular disease. While the study only looked at patients with this specific conditions, this condition is often a subset of the much more common and dangerous cardiovascular disease (CVD), so I think it would not be too much of a stretch to say that taking 1g niacinamide daily would have the same effect in CVD as well, while also potentially being a so-called “disease-modifying therapy” – i.e. having beneficial effects on the underlying pathology causing the fatigue and lack of endurance. Interestingly enough, the study also tested the effects of resveratrol and found it to be not beneficial. So much for the multi-million dollar research performs by Dr. Sinclair in Harvard and the resveratrol company he sold to GSK for more than $700mil.

https://doi.org/10.1038/s41467-024-49092-5

https://www.news-medical.net/news/20240618/Nicotinamide-riboside-boosts-walking-endurance-in-peripheral-artery-disease-The-Over-The.aspx

“…The over-the-counter supplement nicotinamide riboside, a form of vitamin B3, increased the walking endurance of patients with peripheral artery disease, a chronic leg condition for which there are few effective treatments. In a preliminary, randomized, double-blind clinical trial led by Northwestern University and University of Florida scientists, patients who took nicotinamide riboside daily for six months increased their timed walking distance by more than 57 feet, compared to participants who took a placebo. As expected, walking speed declined in those who took a placebo, because peripheral artery disease causes progressive declines in walking performance…(The researchers also tested if resveratrol, a compound best known for being in red wine, could boost the effects of nicotinamide riboside; they found no additional benefits.)”

Via: http://haidut.me/?p=2614

The study below is one of the few to directly challenge the so-called Rate of Living Theory (ROL) that has dominated (and continues to dominate) medical research in aging/longevity. The study demonstrates that administering an OXPHOS uncoupler (which compensatorily increases the metabolic rate and heat production) extended maximum lifespan of the studied organism by up to 25%, while simultaneously also increasing healthspan (the period of time in an organism’s lifespan that is free of major disease). The study used the uncoupler BAM15 to achieve those effects, however this is a very suboptimal choice due to the known toxicity of the chemical resulting mostly likely from the presence of fluorine in the molecule. Had the study used a more benign uncoupler such as 2,4-dinitropheol (DNP), aspirin/salicylates, the active thyroid hormone T3, progesterone, DHEA, salt, etc it is likely that the results would have been much more impressive. Be that as it may, we now have evidence that  the ROL is wrong and the truth about longevity and aging is exactly backwards. Namely, the higher the basal metabolic rate the longer one lives and the healthier one is. Just as importantly, the findings of the study directly question the current established recommendations to exercise rigorously as exhaustive exercise (especially the “endurane” type) is one of the most well-known metabolic suppressors. If an exercise regimen is desired it should consist of mostly concentric exercise, and done only for periods that are so-called glycogen-bound – i.e. exercise should be performed only until the fuel used is primarily glucose, from food of from internal glycogen storage. As soon as glucose is depleted and fat burning (precedes by elevated lipolysis) starts the exercise quickly starts to become detrimental. Not just to the metabolic rate but to the entire organism due to switching over to fat-burning, with the added “bonus” that for most people the fat being released from stores and oxidized will be PUFA as that type of fat is preferentially stored into adipose tissue. And last but not least, the popular press article is one again exposing the cunning nature of scientific “journalism”. Instead of reporting the actual findings of the study, which directly state that metabolic uncoupling and increased metabolic rate/thermogenesis extends lifespan, the article states that “making the cells less efficient at producing energy” is what extends lifespan. While technically correct, the message most people would internalize from the article is that the ROL is correct since for most people reduced energy production implies reduced metabolism.

https://doi.org/10.1111/acel.14107

https://www.msn.com/en-us/health/other/new-findings-suggest-life-span-can-be-increased-by-making-cells-less-efficient-at-producing-energy/ar-BB1iFtX4?item=flightsprg-tipsubsc-v1a?season=2024

“…A new study has shown that BAM15, a compound that makes mitochondria less efficient at producing energy, extended life span in fruit flies and was associated with less body fat and increased muscle function. The paper is titled “Restricting bioenergetic efficiency enhances longevity and mitochondrial redox capacity in Drosophila melanogaster” and is published in the journal Aging Cell.”

“…This current study is the first to show that adding BAM15 to the diet can uncouple mitochondria, extend life span, improve body composition, and protect against age-related decline in motor activity in a fruit fly model of aging. The authors state, “In summary, our findings indicate that mitochondrial uncoupling by BAM15 confers life span extension, improves body composition, and protects against age-related decline in locomotor activity in Drosophila (fruit flies). Collectively, these data support an emerging role for restricting bioenergetic efficiency to maintain mitochondrial redox fitness across the life span.”

Via: http://haidut.me/?p=2612

Honestly, I did not think that an official government admission of the dangers of fluoride would occur in my lifetime. The topic of fluoridated water and its purported myriad of benefits is so  firmly entrenched in both medical and public health dogma that the mere mentioning of water fluoridation in a negative context usually triggers immediate censorship on major social media platforms such as Facebook, YouTube, Instagram, and sometimes even Twitter/X (despite its claims of supporting free speech). Yet, if one were to look at the peer-reviewed literature, it quickly becomes clear that fluoride has multiple negative effects on the human organism, likely stemming from its role as a known thyroid suppressor. Considering that intelligence and behavior largely depend on the metabolic rate, one would expect chronic fluoride exposure through tap water to have strong and lasting negative effects on intelligence and brain health in general. That is exactly what the official Department of Health and Human Services (HHS) report below concludes, and I hope that this report finally leads to local water authorities within the US (and possibly globally as well) changing their position on fluoride and stopping tap water fluoridation.

https://ntp.niehs.nih.gov/whatwestudy/assessments/noncancer/completed/fluoride

https://medicalxpress.com/news/2024-08-links-excessive-fluoride-lowered-iqs.html

“…High levels of fluoride in drinking water may dim the intelligence of children, a new U.S. government report shows. Based on an analysis of published research, the potentially controversial report marks the first time a federal agency has determined there is a link between drinking twice the recommended amount of fluoride and lower IQs in kids. “Since 1945, the use of fluoride has been a successful public health initiative for reducing dental cavities and improving general oral health of adults and children,” the report stated.”

“…But more recent research has pointed to a different problem, suggesting a link between higher levels of fluoride and brain development. Studies in animals showed fluoride could impact cell function in brain regions responsible for learning, memory, executive function and behavior, the AP reported. After more research continued to raise questions, the National Toxicology Program started working on a review of the available studies in 2016. The hope was that it could provide guidance on whether new fluoride-limiting measures were needed.”

Via: http://haidut.me/?p=2610

Curiosity is one of the most common observations in healthy children and is even an established biomarker in diagnosing conditions such as autism, schizophrenia, depression, dementia, etc. Curiosity is known to be very low or even non-existent in older and/or chronically ill people, who are very novelty/curiosity averse and can even become violent when faced with a continuous stream of novel experiences. In other words, healthy people naturally prefer and seek novelty while older/sick people prefer routine and lack of change, and are averse to open-mindedness. Ray mentioned this in several of his articles in the context of energy production, since curiosity/learning is a very energy-intensive process and can be used as a reliable biomarker of overall health in people of all ages. The study below now confirms officially that the active thyroid hormone T3 is the direct driver of curiosity and novelty-seeking behavior, and the steady decline of T3 in aging and chronic diseases would explain the lack of curiosity and open-mindedness in such people. Once again, something even as abstract and seemingly brain-specific as curiosity turns out to be directly controlled by metabolism.

http://dx.doi.org/10.1016/j.cell.2024.07.041

https://www.sciencedaily.com/releases/2024/08/240822125859.htm

“…Thyroid hormone plays a key role in regulating a range of physiologic functions, including metabolism, temperature, heart rate, and growth. It accomplishes this impressive array of activities by interacting with almost every organ system in the body. Yet despite a long history of research on how thyroid hormone influences different organs, its effects on arguably the most crucial organ — the brain — have remained shrouded in mystery. Now, scientists at Harvard Medical School have gained new insights into thyroid hormone’s effects on the brain. The work, conducted in mice and published Aug. 22 in Cell, shows that thyroid hormone changes the wiring of brain circuits in a manner that drives animals to engage in exploratory behavior. By simultaneously changing brain wiring and altering metabolic rate, the researchers concluded that thyroid hormone coordinates the brain and body to produce exploratory behavior when it is most needed — for example, during seasons when animals need to find mates or stockpile resources. “It’s well known that thyroid hormone modulates metabolism, and now we’ve shown that it also modulates exploratory behaviors through direct action on the brain,” said lead author Daniel Hochbaum, research fellow in neurobiology in the Blavatnik Institute at HMS. The findings also help elucidate how low levels of the hormone could lead to depressive states marked by a low desire to explore, while too much could precipitate manic states characterized by an extreme desire for exploration. Thus, the researchers see their work as an important step toward understanding how aberrant levels of thyroid hormone could contribute to certain psychiatric conditions.”

“…Moreover, when researchers induced higher levels of thyroid hormone in the cortex, mice became more willing to explore the environment and take risks. Conversely, when researchers blocked the hormone’s action in only the cortex, the animals no longer changed how much they explored based on thyroid hormone levels. “This told us that thyroid hormone is doing important things directly in the cortex,” Hochbaum said.”

Via: http://haidut.me/?p=2608

I know this post will make me a lot of new enemies among the anti-retinol crowd, but the findings are too important not to share with my readers since the study was not only with humans, but humans in a very compromised state of health (heart failure). This suggests that in healthier humans the anti-depressant effects may be even more pronounced. While the study did not opine on the main mechanism of action, it does mention the crucial role of vitamin A in dampening inflammation, as well as its crucial role in steroidogenesis (including thyroid). Both of those pathways are very important in depressed patients, who are almost always found to have chronic inflammation and reduced levels of thyroid hormones as well as “neurosteroids” such as pregnenolone, progesterone, DHEA, testosterone, etc while also both reducing cortisol (a known causative steroid in depression) synthesis and blocking its effects at the receptor level.

https://ods.od.nih.gov/factsheets/VitaminA-HealthProfessional/

https://onlinelibrary.wiley.com/doi/10.1002/ehf2.14935

https://www.healio.com/news/cardiology/20240723/vitamin-a-intake-may-improve-depressive-symptoms-in-people-with-heart-failure

“…The researchers observed that approximately 85% of participants with depression reported daily vitamin A intake of less than 731.38 µg. Wang and colleagues found that compared with patients with low daily vitamin A intake, depression was less likely in patients at increasing daily intake levels of vitamin A, which became significant above 731.38 µg daily. Moreover, daily vitamin A intake of 731.38 µg or more compared with low intake was significantly associated with lower odds for depression among participants with HF aged 65 years or older, men and participants with hyperlipidemia or chronic kidney disease. “Vitamin A acts as an antioxidant, protecting against oxidative damage and reducing inflammation by inhibiting the production of pro-inflammatory cytokines. By mitigating these processes, vitamin A may contribute to reduce the incidence of depression in HF patients,” the researchers wrote. “Vitamin A is involved in the regulation of various hormones, including cortisol and thyroid hormones, which have been implicated in depression. Chronic stress, commonly experienced by patients with HF, can dysregulate the hypothalamic-pituitary-adrenal (HPA) axis, leading to elevated cortisol levels,” they wrote. “Adequate vitamin A intake may contribute to optimal thyroid function and reduce the risk of depression in patients with HF.”

Via: http://haidut.me/?p=2606