Gut microbial metabolites in depression: understanding the biochemical mechanisms

Gastrointestinal and central function are intrinsically connected by the gut microbiota, an ecosystem that has co-evolved with the host to expand its biotransformational capabilities and interact with host physiological processes by means of its metabolic products.

Abnormalities in this microbiota-gut-brain axis have emerged as a key component in the pathophysiology of depression, leading to more research attempting to understand the neuroactive potential of the products of gut microbial metabolism.

This review explores the potential for the gut microbiota to contribute to depression and focuses on the role that microbially-derived molecules – neurotransmitters, short-chain fatty acids, indoles, bile acids, choline metabolites, lactate and vitamins – play in the context of emotional behaviour.

The future of gut-brain axis research lies is moving away from association, towards the mechanisms underlying the relationship between the gut bacteria and depressive behaviour.

We propose that direct and indirect mechanisms exist through which gut microbial metabolites affect depressive behaviour: these include (i) direct stimulation of central receptors, (ii) peripheral stimulation of neural, endocrine, and immune mediators, and (iii) epigenetic regulation of histone acetylation and DNA methylation.

Elucidating these mechanisms is essential to expand our understanding of the aetiology of depression, and to develop new strategies to harness the beneficial psychotropic effects of these molecules.

Overall, the review highlights the potential for dietary interventions to represent such novel therapeutic strategies for major depressive disorder.

Source:

Microbial Cell

Bile, Liver, Newsletter-Oct-29-23

Why pain under your right side ribs may signal gallbladder trouble

If you’ve ever felt a sharp, cramping pain under your ribs on the right side of your abdomen, it likely signals a problem with your gallbladder. The gallbladder is a small organ that stores and concentrates bile created by the liver. Bile helps digest fats from the foods we eat. Issues like gallstones or inflammation can prevent proper bile flow and cause gallbladder pain.

Gallstones form when hardened deposits of cholesterol and bile salts build up in the gallbladder or bile ducts. These stones irritate the gallbladder wall, which can trigger painful spasms. Gallstones also block the release of bile, causing it to back up into the gallbladder. This added pressure on the organ results in the agonizing pain under the ribs. This same pain can be referred to an area between the shoulder blades.

In addition to gallstones, inflammation from infections, bile duct issues, and other gallbladder diseases can all impair its ability to release bile. Without enough bile, the gallbladder never fully empties and bile becomes sludgy and concentrated. The excess bile can also crystallise into new gallstones, fuelling the problem.

Symptoms of an underperforming gallbladder extend beyond pain under the ribs. Some other signs include constipation, indigestion after meals, bloating, light coloured stools, nausea, and vomiting.

Making dietary changes to maintain bile flow may help relieve gall bladder pain. These include eating bitter herbs, staying hydrated, and limiting processed foods. Supplements that include whole beet concentrate like BetaTCP can improve the flow of bile in a few days, clearing the pain and improving digestion.

Don’t ignore recurring pain under your ribs as it often indicates problems in the biliary system.

Microbiome, PCOS, α-Lactalbumin

Positive Effects of α-Lactalbumin in the Management of Symptoms of Polycystic Ovary Syndrome

Nutrients

To date, the involvement of α-Lactalbumin (α-LA) in the management of polycystic ovary syndrome (PCOS) refers to its ability to improve intestinal absorption of natural molecules like inositols, overcoming the inositol resistance. However, due to its own aminoacidic building blocks, α-LA is involved in various biological processes that can open new additional applications.

A great portion of women with PCOS exhibit gastrointestinal dysbiosis, which is in turn one of the triggering mechanisms of the syndrome. Due to its prebiotic effect, α-LA can recover dysbiosis, also improving the insulin resistance, obesity and intestinal inflammation frequently associated with PCOS. Further observations suggest that altered gut microbiota negatively influence mental wellbeing.

Depressive mood and low serotonin levels are indeed common features of women with PCOS. Thanks to its content of tryptophan, which is the precursor of serotonin, and considering the strict link between gut and brain, using α-LA contributes to preserving mental well-being by maintaining high levels of serotonin.

In addition, considering women with PCOS seeking pregnancy, both altered microbiota and serotonin levels can induce later consequences in the offspring. Therefore, a deeper knowledge of potential applications of α-LA is required to transition to preclinical and clinical studies extending its therapeutic advantages in PCOS.

NOTE: α-LA is high in whey protein

Metabolic syndrome, Microbiome, PCOS

Exploration of the Relationship Between Gut Microbiota and Polycystic Ovary Syndrome (PCOS): a Review

Geburtshilfe Frauenheilkd

Polycystic ovary syndrome (PCOS) is an endocrine and metabolic syndrome (MS) with a complex etiology, and its pathogenesis is not yet clear. In recent years, the correlation between gut microbiota (GM) and metabolic disease has become a hot topic in research, leading to a number of new ideas about the etiology and pathological mechanisms of PCOS.

The literature shows that GM can cause insulin resistance, hyperandrogenism, chronic inflammation and metabolic syndrome (obesity, diabetes) and may contribute to the development of PCOS by influencing energy absorption, the pathways of short chain fatty acids (SCFA), lipopolysaccharides, choline and bile acids, intestinal permeability and the brain–gut axis.

As part of the treatment of PCOS, fecal microbiota transplantation, supplementation with prebiotics and traditional Chinese medicine can be used to regulate GM and treat disorders.

This article reviews possible mechanisms and treatment options for PCOS, based on methods which target the GM, and offers new ideas for the treatment of PCOS.

anxiety, Depression, The Pill

Feel like a different person on the pill? Here’s how it affects your mood

Ideas, Ted.com

Mood-related issues like anxiety and depression are super-common among women on the pill. Almost half of all women who go on the pill stop using it within the first year because of intolerable side effects, and the one most frequently cited is unpleasant changes in mood. Sometimes it’s intolerable anxiety; other times, it’s intolerable depression; or maybe both simultaneously. And even though some women’s doctors may tell them that those mood changes aren’t real or important, a growing body of research suggests otherwise.

… according to the research, you might have a greater risk of experiencing negative mood effects on the pill if:

You have a history of depression or mental illness (although there is also evidence that the pill can stabilize mood in certain women with mental illness).
You have a personal or family history of mood-related side effects on the birth control pill.
You are taking progestin-only pills.
You are using a non-oral product.
You are taking multi-phasic pills (pills with an increasing dose of hormones across the cycle rather than a constant dose).
You are 19 or younger.

Astragalus, Bile, Diabetes, FXR

Total flavonoids of Astragalus Ameliorated Bile Acid Metabolism Dysfunction in Diabetes Mellitus

Evid Based Complement Alternat Med.

Astragalus Radix is one of the common traditional Chinese medicines used to treat diabetes. However, the underlying mechanism is not fully understood.

Flavones are a class of active components that have been reported to exert various activities. Existing evidence suggests that flavones from Astragalus Radix may be pivotal in modulating progression of diabetes.

In this study, total flavones from Astragalus Radix (TFA) were studied to observe its effects on metabolism of bile acids both in vivo and in vitro. C57BL/6J mice were treated with STZ and high-fat feeding to construct diabetic model, and HepG2 cell line was applied to investigate the influence of TFA on liver cells.

We found a serious disturbance of bile acids and lipid metabolism in diabetic mice, and oral administration or cell incubation with TFA significantly reduced the production of total cholesterol (TCHO), total triglyceride, glutamic oxalacetic transaminase (AST), glutamic-pyruvic transaminase (ALT), and low-density lipoprotein (LDL-C), while it increased the level of high-density lipoprotein (HDL-C). The expression of glucose transporter 2 (GLUT2) and cholesterol 7α-hydroxylase (CYP7A1) was significantly upregulated on TFA treatment, and FXR and TGR5 play pivotal role in modulating bile acid and lipid metabolism.

This study supplied a novel understanding towards the mechanism of Astragalus Radix on controlling diabetes.

Bile, Diabetes, FXR

Bile acid metabolism and the pathogenesis of type 2 diabetes

Curr Diab Rep.

T2D is a growing health problem world-wide, but the currently available strategies for therapy and prevention are insufficient. Recent observations indicate that bile acid homeostasis is altered in T2D. Bile acids are metabolic regulators that act as signaling molecules through receptor-dependent and -independent pathways. The most prominent signaling molecules mediating bile acid signaling are the nuclear receptor FXR and the membrane receptor TGR5. Both are implicated in the regulation of lipid, glucose and energy metabolism. Dysregulation of these pathways might contribute to the development of T2D and associated metabolic complications. Interestingly, data from studies with bile acids or bile acid sequestrants indicate that the manipulation of bile acid homeostasis might be an attractive approach for T2D therapy. In this review, we summarize the mechanisms of bile-acid-mediated metabolic control that might be of relevance in the pathogenesis of T2D.
Keywords: Animals, Bile Acids and Salts, metabolism, Diabetes Mellitus, Type 2, metabolism, physiopathology, Dyslipidemias, metabolism, physiopathology, Humans, Obesity, metabolism, physiopathology

Keywords: Bile acids, T2D, FXR, TGR5, bile acid sequestrants, obesity, dyslipidemia, NAFL

Bile, Diabetes

Understanding Bile Acid Signaling in Diabetes: From Pathophysiology to Therapeutic Targets

Diabetes and metabolism Journal

Diabetes and obesity have reached an epidemic status worldwide. Diabetes increases the risk for cardiovascular disease and non-alcoholic fatty liver disease.

Primary bile acids are synthesized in hepatocytes and are transformed to secondary bile acids in the intestine by gut bacteria. Bile acids are nutrient sensors and metabolic integrators that regulate lipid, glucose, and energy homeostasis by activating nuclear farnesoid X receptor and membrane Takeda G protein-coupled receptor 5.

Bile acids control gut bacteria overgrowth, species population, and protect the integrity of the intestinal barrier. Gut bacteria, in turn, control circulating bile acid composition and pool size.

Dysregulation of bile acid homeostasis and dysbiosis causes diabetes and obesity.

Targeting bile acid signaling and the gut microbiome have therapeutic potential for treating diabetes, obesity, and non-alcoholic fatty liver disease.

Keywords: Bile acids and salts, Gastrointestinal microbiome, Non-alcoholic fatty liver disease, Receptors, cytoplasmic and nuclear, Receptors, G-protein-coupled

FXR, Insulin resistance, Microbiome, PCOS

Intestinal Flora is a Key Factor in Insulin Resistance and Contributes to the Development of Polycystic Ovary Syndrome

Endocrinology

The key gut microbial biomarkers for polycystic ovarian syndrome (PCOS) and how dysbiosis causes insulin resistance and PCOS remain unclear.

Objective: To assess the characteristics of intestinal flora in PCOS and explore whether abnormal intestinal flora can affect insulin resistance and promote PCOS and whether chenodeoxycholic acid (CDCA) can activate intestinal farnesoid X receptor (FXR), improving glucose metabolism in PCOS.

Results: Bacteroides was significantly enriched in treatment-naïve PCOS patients. The enrichment in Bacteroides was reproduced in the PCOS mouse model. Gut microbiota removal ameliorated the PCOS phenotype and insulin resistance and increased relative FXR mRNA levels in the ileum and serum fibroblast growth factor 15 levels. PCOS stool-transplanted mice exhibited insulin resistance at 10 weeks but not PCOS. Treating the PCOS mouse model with CDCA improved glucose metabolism.

Conclusions: Bacteroides is a key microbial biomarker in PCOS and shows diagnostic value. Gut dysbiosis can cause insulin resistance. FXR activation might play a beneficial rather than detrimental role in glucose metabolism in PCOS.

Antidepressants, Endometriosis, Neurotransmitters, Pain

Chronic pain:antidepressants not painkillers recommended

BBC

Doctors are being advised not to prescribe common painkillers, including paracetamol and ibuprofen, for patients with chronic pain not caused by an injury or other medical condition.

The National Institute of Health and Care Excellence (NICE) said there was little evidence they help.

And it suggests there is evidence long-term use can be harmful.

Its draft guidance recommends antidepressants, acupuncture or psychological therapy instead.

… They could also consider recommending a course of cognitive therapy, aimed at helping patients accept their condition or change the way they thought about it.

… The guidelines acknowledged there is a lot of uncertainty in this diagnosis, and “normal or negative test results can be communicated in a way that is perceived as being dismissive of pain”.

When it comes to chronic pain more broadly – defined as pain that “persists or recurs” for more than three months, no matter the cause – NICE advises using these new guidelines alongside existing guidance on the management of specific conditions.

That includes headaches, back pain, arthritis and endometriosis.

Antidepressants, Neurotransmitters

Tapering strips

Tapering Strip

The reduction or discontinuation of psychiatric medications such as antidepressants, antipsychotics or anxiolytics can cause physical and psychological withdrawal and rebound symptoms. Withdrawal symptoms may be so severe that patients are unable to continue reducing the dose, regardless of the medication’s efficacy.

In 2010, the Tapering Project was started to address these problems through the development of tapered doses of medication provided in strip packaging: tapering strips.

Tapering strips allow patients to regulate the tempo of their dose reduction over time and enable them to taper more gradually, conveniently and safely than is possible using currently available standard medication, thereby preventing withdrawal symptoms.

What

In a tapering strip, medication is packaged in a roll or strip of small daily pouches. Each pouch is numbered and has the same or slightly lower dose than the package before it.p

How

Strips come in series covering 28 days and patients can use one or more strips to regulate the tempo of their dose reduction over time. Dose and day information printed on each pouch allow patients to precisely record and monitor the progress of their reduction.

For whom?

Tapering strips are developed for medication in cases where doing so improves the medical care available and meets an unmet need. See the list with available tapering strips.

Antidepressants, Neurotransmitters

Researchers Provide Guidance for Reducing and Stopping Psychiatric Drugs

Mad in America

In a new article in European Neuropsychopharmacology, researchers Mark Horowitz and David Taylor provide guidance for tapering psychiatric drugs, whether for full discontinuation or to reduce the dose. They suggest a slow, individualized taper to minimize withdrawal effects.

“The general principle when reducing or stopping psychiatric medications is as follows. Make a small reduction, monitor for withdrawal effects or destabilization of the patient, then ensure stability before making further reductions. Reductions should probably be made in smaller and smaller increments because of the pharmacology of the drugs; the final dose before completely stopping will need to be very small.”

Horowitz and Taylor have previously written about this approach for antidepressants in Lancet Psychiatry and for antipsychotics in JAMA Psychiatry (with Sir Robin Murray).

…Some people may require months or even years to slowly decrease their dose before eventually stopping the drug. The researchers write:

“Withdrawal effects (and relapse) might be minimized by stopping psychiatric drugs over a period long enough for underlying adaptations to the drug to resolve.”

According to the researchers, based on studies of the drugs’ effects on the brain, psychiatric drugs impact the brain along with a hyperbolic relationship. That is, at low doses, small adjustments have huge impacts—but at high doses, even large adjustments have less of an impact.

“The relationship between dose of a psychiatric drug and its effects is hyperbolic,” they write. “This is a consequence of the law of mass action: when there are few molecules of a drug present at the site of action, every additional molecule has a large incremental effect, but when higher concentrations are present each additional molecule has less and less effect, as receptors become saturated.”

This means that dose reductions should not be linear (reduced by the same amount each time, e.g., 40, 30, 20, 10, 0 mg). Instead, one strategy is to reduce the current dose by 10% each time, especially ensuring that the last adjustment—to full discontinuation—is very small.

Fertility, Microbiome, Pregnancy, Probiotcs, Vaginal health

The vaginal microbiome – fertility and successful pregnancy

FX medicine

A specialised microbial community in humans is the vaginal microbiome. Successful human reproduction depends heavily on the correct balance of these microbes.

An optimal vaginal microbiome results in the production of lactic acid and hydrogen peroxide, maintaining a level of acidity that keeps pathogenic bacteria at bay.

When the vaginal community becomes disturbed, on the other hand, acidity decreases. Pathogenic or other opportunistic bacteria may then invade, which can cause bacterial vaginosis. This is best described as a state of dysbiosis rather than infection.

Research suggests that probiotic supplementation may be of benefit in maintaining homeostasis of the vaginal microbiome thereby reducing the risk of infection, dysbiosis and subsequent inflammation and immune dysfunction.

Lactic acid bacteria, Microbiome, PCOS

Lactic Acid Bacteria Alleviate Polycystic Ovarian Syndrome by Regulating Sex Hormone Related Gut Microbiota

Royal Society of Chemistry

Polycystic ovarian syndrome (PCOS) is a common endocrine disease across the world. Because gut microbiota play a key role in the pathogenesis of PCOS, probiotics may alleviate PCOS symptoms through the regulation of intestinal flora. The effects of 8 lactic acid bacterial strains on PCOS were investigated. Letrozole was used to produce a PCOS rat model and a 4-week-strain-intervention was performed. Diane-35, as a clinical PCOS treatment medicine, was effective in attenuating rats’ reproductive disorders.

Lactobacillus plantarum HL2 was protective against ovary pathological changes and restored luteinizing hormone, follicle stimulating hormone and testosterone levels.

Bifidobacterium longum HB3 also alleviated ovary abnormalities and decreased testosterone levels.

Administration of lactic acid bacteria up-regulated short-chain fatty acid levels.

Based on 16S rRNA sequencing, lactic acid bacteria improved letrozole induced gut microbiota dysbiosis with different degrees.

Akkermansia, Roseburia, Prevotella, Staphylococcus and Lactobacillus genera were correlated with sex hormone levels. Some of the sex hormone-related gut microbiota were restored by treatment with the strains.

These results demonstrated that lactic acid bacteria alleviated PCOS in a rat model by regulating sex hormone related gut microbiota. Modifying gut microbiota by probiotic interventions may thus be a promising therapeutic option for PCOS.

Bile, IL-22, Microbiome, PCOS

Gut microbiota–bile acid–IL22 axis orchestrates PCOS

Nature

Polycystic ovary syndrome (PCOS) is characterized by androgen excess, ovulatory dysfunction and polycystic ovaries¹, and is often accompanied by insulin resistance².

The mechanism of ovulatory dysfunction and insulin resistance in PCOS remains elusive, thus limiting the development of therapeutics. Improved metabolic health is associated with a relatively high microbiota gene content and increased microbial diversity^3,4.

This study aimed to investigate the impact of the gut microbiota and its metabolites on the regulation of PCOS-associated ovarian dysfunction and insulin resistance. Here, we report that Bacteroides vulgatus was markedly elevated in the gut microbiota of individuals with PCOS, accompanied by reduced glycodeoxycholic acid and tauroursodeoxycholic acid levels.

Transplantation of fecal microbiota from women with PCOS or B. vulgatus-colonized recipient mice resulted in increased disruption of ovarian functions, insulin resistance, altered bile acid metabolism, reduced interleukin-22 secretion and infertility.

Mechanistically, glycodeoxycholic acid induced intestinal group 3 innate lymphoid cell IL-22 secretion through GATA binding protein 3, and IL-22 in turn improved the PCOS phenotype.

This finding is consistent with the reduced levels of IL-22 in individuals with PCOS. This study suggests that modifying the gut microbiota, altering bile acid metabolism and/or increasing IL-22 levels may be of value for the treatment of PCOS.

Cortisol, Emotions, Microbiome, Mind, Nutrition and supplements, Prebiotic, Stress Relief

Prebiotic intake reduces the waking cortisol response and alters emotional bias in healthy volunteers

Psychopharmacology

There is now compelling evidence for a link between enteric microbiota and brain function. The ingestion of probiotics modulates the processing of information that is strongly linked to anxiety and depression, and influences the neuroendocrine stress response.

This study found that taking a prebiotic called galactooligosaccharides for three weeks significantly reduced the amount of cortisol, a primary stress hormone in the body.

COMT, Genetics, Neurotransmitters, Oestrogen, Stress Relief

Catechol-O-methyltransferase Features

Catechol-O-Methyltransferase (COMT) is one of the several enzymes that degrade dopamine, epinephrine, and norepinephrine. COMT breaks down dopamine mostly in the part of the brain responsible for higher cognitive or executive function (prefrontal cortex).

COMT helps break down estrogen byproducts that have the potential to cause DNA mutations and cause cancer.

If you have higher COMT levels:

Mucuna to increase dopamine,
Tyrosine to increase dopamine,
EGCG/Tea (COMT inhibitor),
Epicatechins/Chocolate (COMT inhibitor),
Luteolin

If you have lower levels of COMT, the following may counteract some of the effects of the gene:

SAM-e – however, this can increase dopamine levels in people who already have high dopamine.
Methyl Guard Plus to ensure adequate B6, B12, folate and betaine to support the formation of S-adenosylmethionine and prevent elevated homocysteine; S-adenosylhomocysteine inhibits COMT activity.
Ensure adequate anti-oxidants to prevent oxidation of dopamine and pro-carcinogenic 4-hydroxyestrogens,
Magnesium Citrate (magnesium is a cofactor)
Be careful of the following supplements that are the targets of COMT: quercetin, rutin, luteolin, EGCG, catechins, Epicatechins, Fisetin, Ferulic acid, Hydroxytyrosol
Avoid excessive alcohol consumption. Since alcohol-induced euphoria is associated with the rapid release of dopamine in limbic areas, low activity COMT variant would have a relatively low dopamine inactivation rate, and therefore would be more vulnerable to the development of alcohol dependence.
Avoid stimulants, especially amphetamines. Amphetamines may do worse with people who are AA, but later studies did not replicate this. It could be differences in study design.
Avoid chronic stress (stress hormones require COMT for degradation and compete with estrogens),

Catechol Estrogens, Cancer and Autoimmunity

Catechol estrogens form from CYP enzymes breaking down Estradiol and Estrones. Catechol estrogens can break DNA and cause cancer and autoimmune conditions. COMT methylates (using SAM) and inactivates these catechol estrogens (2- and 4-hydroxycatechols). The products of COMT methylation are 2- and 4-o-methylethers, which are less harmful and excreted in the urine (they have anti-estrogen properties). However, if COMT is inhibited too much either because of genetics or dietary inhibition, it should result in higher levels of catechol estrogens, especially if glucuronidation and sulphation pathways are not working. 4-Hydroxyestrone/estradiol was found to be carcinogenic in the male Syrian golden hamster kidney tumour model, whereas 2-hydroxylated metabolites were without activity. 4-Hydroxyestrogen can be oxidized to quinone intermediates that react with purine base of DNA, resulting in depurination adduct that generates cancerous mutations. Quinones derived from 2-hydroxyestrogens are less toxic to our DNA. Estrone and estradiol are oxidized to a lesser amount to 2-hydroxycatechols by CYP3A4 in the liver and by CYP1A in extrahepatic tissues or to 4-hydroxycatechols by CYP1B1 in extrahepatic sites, with the 2-hydroxycatechol being formed to a larger extent .

It has been observed that tissue concentration of 4-hydroxyestradiol is highest in malignant cancer tissue, out of all the estrogens. The concentration of these Catechol Estrogens in the hypothalamus and pituitary are at least ten times higher than parent estrogens. Catechol Estrogens have potent endocrine effects and play an important role in hormonal regulation (those produced by hypothalamus and pituitary).

Increased availability of estrogen and estradiol for binding and hypothalamic sites would facilitate the formation of Catechol Estrogens. These estrogens affect Luteinizing Hormone (LH) and maybe follicle-stimulating hormone (FSH) and prolactin. Catecholestradiol competes with estradiol for estrogen binding sites in the anterior pituitary gland and hypothalamus and dopamine binding sites on anterior pituitary membranes.

Other possible mechanisms of inactivation of these catechol estrogens include conjugation by glucuronidation and sulphation. High concentration of 4-hydroxylated metabolites caused insufficient production of methyl, glucuronide or sulfate conjugate which in turn results in catechol estrogen toxicity in cells and oxidation to semiquinone and quinone, which may reduce glutathione (GSH). These oxidation products could lead to DNA mutations. The quinone/semiquinone redox system produces superoxide ions (O2¯ ) which can react with NO to form peroxynitrite, which could cause DNA damage. In summary, CEs lead to the production of potent ROS, capable of causing DNA damage, thus playing an important role not only in causing cancer but also in systemic lupus erythematosus (SLE) and Rheumatoid Arthritis. The abilities of the estrogens to induce DNA mutations were ranked as follows: 4-hydroxyestrone (most damaging) > 2-hydroxyestrone > 4-hydroxyestradiol >2-hydroxyestradiol > > Estradiol, Estrone.

Mental health

What ‘Peri/menopausal Syndrome’ Does to Women’s Brains

More misinformation in this article from the Atlantic – starting with the title – “What Menopause Does to Women’s Brains”.

It’s not the menopause that’s causing the problems with women’s brains – the menopause is a natural and normal rite of passage, like puberty. The title should be – What Peri-menopausal Syndrome Does to Women’s Brains.

Peri/menopausal Syndrome – as I now call it – is the constellation of symptoms in peri/menopause that includes a decline in brain function.

The articles gets the data right:

Two-thirds of all Alzheimer’s patients are women. Why?

For women, there is a marked decline in brain energy and an increase in Alzheimer’s plaques as they go from premenopausal to fully menopausal.

Estrogen is a neuroprotective hormone. When it declines, the brain is left more vulnerable. So if a woman is somehow predisposed to Alzheimer’s, that’s when the risk manifests itself in her brain.

The loss of estrogen means that glucose metabolism in the brain, its primary fuel, is reduced by about 20 to 25 per cent. That’s why women experience that they’re off their game. They still can play the game, just not as well.

If naturally low glucose metabolism in the brain of a peri/menopausal woman is causing cognitive problems, then the answer is simple: peri/menopausal women MUST switch their energy source from glucose to FAT. This will provide the brain with the energy that it needs and not only will brain function improve, but all the other symptoms completely disappear.

The author goes on to say:

“At one point during my interview with Mosconi, she happened to mention that women who undergo hysterectomies have a higher risk of Alzheimer’s. A chill shot up my spine. In my early 40s, I had a hysterectomy to remove a uterus beleaguered by adenomyosis. I’m certain no one ever warned me of the risk pre-op, even though the information was already out there. I couldn’t have forgone the surgery; my adenomyosis had left me fatally anemic. But I at least could have been informed. I was so upset to learn this, I had to shut off the digital recorder to catch my breath.”

Women need to know that there is a nutritional and lifestyle approach that can completely eliminate this very real worry. The low carb/high fat approach I have developed works to resolve symptoms in 100% of women in my clinic and in the PeriMenoFix course.

READ THE ARTICLE

Brain, Dementia, Exercise, Mental health

How Exercise Lowers the Risk of Alzheimer’s by Changing Your Brain

Time

White matter hyperintesities are areas of the brain where damage has occurred to the neurons. These areas are associated with peri/menopausal hot flushes because the brain is starved of energy and is cannibalising itself for energy.

White matter hyperintesities are also associated with dementia and Alzheimer’s but recent research shows that exercise can help to reduce the risks of decreasing brain function:

“…as people age, the presence of Alzheimer’s-related brain changes increases—including the buildup of amyloid, slower breakdown of glucose by brain cells, shrinking of the volume of the hippocampus (central to memory), and declines in cognitive function measured in standard recall and recognition tests.

But they found that in people who reported exercising at moderate intensity at least 150 minutes a week, as public health experts recommend, brain scans showed that these changes were significantly reduced and in some cases non-existent compared to people who were not active. “The association between age and Alzheimer’s brain changes was blunted,” says Okonkwo, “Even if [Alzheimer’s] got worse, it didn’t get worse at the same speed or rate among those who are physically active as in those who are inactive.”

Antidepressants, Brain, Medication, Mental health

Menopausal women wrongly prescribed antidepressants which make their symptoms worse

The Independent

‘They are not mentally ill, antidepressants are not appropriate. Once they have the label, it doesn’t help them,’ says expert.

Hot flushes and night sweats are the most well-known symptoms in peri/menopause, but the most common ones are anxiety, depression and brain fog. So many women who are looking for help get prescribed anti-depressants, despite the fact that:

“Menopause guidelines are very clear that antidepressants should not be given first-line for low mood associated with the menopause because there is no evidence that they will help.”

Editor’s note:

The reason why anti-depressants don’t help is that these medications target neurotransmitters like serotonin. But the loss of brain function that is associated with peri/menopause is not a neurotransmitter problem, it’s an energy problem.

During peri/menopause the brain becomes less and less able to use carbohydrates for energy and switches to mainly using fat for energy. This means that unless a low carb/high-fat diet is being followed, the brain will become starved of energy, leading to anxiety, depression and brain fog.

Switching to a low carb/high-fat diet can resolve brain issues in just a few weeks.

Ageing, Lifestyle, Mental health

Happy ever after: 25 ways to live well into old age

Guardian

Determined to enjoy longer and healthier lives, two women researched the science to find the key. Here, they share what they discovered.

When Susan Saunders was 36, her mother was diagnosed with severe dementia. “I had a toddler, a newborn, a full-time job as a TV producer – and I became a carer as well.” As a teenager, she had watched her mum care for her own mother, who had the same condition. “I became determined to do everything I could to increase my chances of ageing well.”

Annabel Streets’ story is similar. When she was a student, her grandfather died from cancer months after he retired; later, she watched her mother care for her grandmother, who lived with dementia and crippling rheumatoid arthritis for nearly 30 years. “When I developed a chronic autoimmune disease, I knew things had to change. But by then I had four young children and there was precious little time for my own health.”

Together, Saunders and Streets started researching the latest science on how to have a healthier, happier old age and how to apply it to their own lives, and blogged about their findings for five years. Their Age Well Project has now been published as a book, compiling almost 100 shortcuts to health in mid-and later life – and Streets and Saunders, who are both in their 50s, say they have never been in better health.

What did they learn?

Brain, Dementia, Mental health, Nutrition and supplements

5 Ways to Fuel Your Brain

Tony Robbins

We tend to think that a loss of mental acuity is just part of getting older — but age is not the only contributing factor to cognitive decline. Our lifestyle also plays a key role. Failing to follow a nutritious diet, a lack of sleep and exercise, ongoing stress, smoking, drinking alcohol excessively and environmental pollutants can all damage our brain cells.

Fortunately, mental deterioration is not irreversible. In fact, the brain is incredibly dynamic and has the potential and the ability to change at any point throughout our entire life – and you have the power to enhance your brain function, protect your brain from damage and counteract the effects of aging! That is, if you’re willing to fuel the brain and tweak your everyday decisions.

Here are 5 small changes you can make in your life that can mean big differences in your cognitive abilities.

Depression, Hot flushes, Mental health

Moderate-severe hot flashes significantly increase depression risk

LiebertPub

A new study of more than 2,000 perimenopausal and menopausal women showed that moderate-severe vasomotor symptoms (hot flashes or night sweats) were an independent and significant risk factor for moderate-severe depression. Researchers explored the controversial link between hot flashes and depressive symptoms by focusing on more severe forms of both conditions and concluding that there is likely a common underlying cause, as reported in an article published in Journal of Women’s Health, a peer-reviewed publication from Mary Ann Liebert, Inc., publishers. The article is available free on the Journal of Women’s Health website until May 18, 2017.

Data presented in the article entitled “Moderate-Severe Vasomotor Symptoms Are Associated with Moderate-Severe Depressive Symptoms,” demonstrate that among a group of women ages 40-65, those with moderate-severe hot flashes were significantly more likely to have moderate-severe depression than women with no or mild vasomotor symptoms. Roisin Worsley, MBBS, Robin Bell, PhD, Pragya Gartoulla, Penelope Robinson, and Susan Davis, MBBS, Monash University, Melbourne, Australia, found hot flashes, depressive symptoms, and use of antidepressant medication to be common in the age range of women included in the study. The researchers also examined whether or not moderate-severe depression was associated with a greater likelihood of psychotropic medication use, smoking, or binge drinking at least once a week.

Breast cancer, Gut, Microbiome, Oestrogen, Peri/menopause

Gut Microbes linked to estrogen breakdown in menopause

MedScape

Postmenopausal women with a more diverse population of gut bacteria may be more efficient at breaking down estrogen, a new study suggests. Because estrogen plays a role in causing breast cancer, researchers speculate a healthy bacterial population may lower the risk for cancer.

“The composition and diversity of the intestinal microbiota were associated with patterns of estrogen metabolism that are predictive of the risk of breast cancer in postmenopausal women,”

Estrogen is metabolized in the liver and in other tissues such as the breast, yielding fragments that are excreted in urine or, through bile, into the gut. Gut microbes can degrade these metabolites, allowing them to be reabsorbed into the bloodstream and further recycled in the liver. Dr. Fuhrman and colleagues suggest that women whose gut bacteria more efficiently process estrogen may have a lowered risk for breast cancer.

Microbiome, Peri/menopause, Vaginal dryness, Vaginal health

Changing vaginal microbiome triggers and relieves atrophy

MedScape

Postmenopausal vulvovaginal atrophy is associated with age-related changes in the vaginal microbiome, with a shift from Lactobacillus-dominated strains in premenopause to a predominance of anaerobic organisms, new research shows.

“We have not yet identified specific interventions, but we are interested in pursuing personalized selections of probiotics and prebiotics for a given woman,” said lead investigator Rebecca Brotman, PhD.

“We have been advocating probiotics or prebiotics to improve vaginal health for almost 30 years,” said Gregor Reid, PhD.

“I 100% support the conclusions of this work. It is nice to see confirmation of work we published in 2011, with an aberrant microbiota associated with some cases of vulvovaginal atrophy,” Dr. Reid told Medscape Medical News (PLoS One, 2011;6:e26602).

Gut microbial metabolites in depression: understanding the biochemical mechanisms

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Sandra Ishkanes Functional Medicine Practitioner BSc MA DipION sandra@gynecologic.dream.press Brighton, UK

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Sandra Ishkanes
Functional Medicine Practitioner
BSc MA DipION

sandra@gynecologic.dream.press
Brighton, UK