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Sept 12^th – MentaHeart

Sept 19^th – SLC Amare event – streamed LIVE

Sept 26^th – Kid’s Mood+ and Amare Kids Pack

Oct 3^rd – HempGBX+

Oct 10^th – Recap of International Gaming Summit on Mental Health (from Toronto)

Oct 17^th – Project b3 research results (which I will be presenting on Oct 21^st at the International Society for Nutritional Psychiatry Research (ISNPR) in London

Oct 24th – West Palm Beach Amare event – streamed LIVE

Oct 31 – Recap and highlights from the ISNPR Conference

Nov 7^th – OmMega new formulation (as it will become available on Nov 1)

Nov 14^th – Holiday Stress Resilience with Amare’s Updated Product Line

Nov 21^st – Costa Rica (no Deep Dive)

Nov 28^th – Thanksgiving (no Deep Dive)

Dec 5^th – Open mic night – bring your questions

Dec 12^th – Synbiotics: the synergistic relationship between probiotics and prebiotics

Dec 19^th – Amare’s commitment to quality assurance & sustainable sourcing practices

Dec 26^th – Day after Xmas (no Deep Dive)

Very good article in the NY Times recently (Aug 29) about managing your “mental illness” at work. There are some excellent tips in my highlighted version below (original here), but I don’t agree that the depression, anxiety and PTSD that the author writes about are “mental illnesses.”

Rather, as I’ve been teaching about for the last 20 years, these are examples of how we describe being low on the “Mental Wellness Continuum” (depression at the low end; feeling “fine” in the middle; and feeling and performing optimally at the high end of the continuum). Science is now showing us that mental wellness can be wonderfully improved by a wide range of natural lifestyle interventions including stress management, mindfulness meditation, improved sleep quality, functional movement, mental wellness diets, targeted supplements, and many others (including some of the “work around” tips below).

Image credit = Lilli Carré

How to Manage Your Mental Illness at Work

If you suffer from depression, anxiety, PTSD or another mental illness, here are some real-world tips to help you stay happy and healthy at work.

By Eric Ravenscraft

Published Aug. 29, 2019 / Updated Sept. 8, 2019

I dropped my freshly cooked lunch all over the carpet. It wasn’t the reason I broke down just outside my office, but it was all the excuse I needed. I fell to my knees, screamed at the carpet, and cried as I shakily cleaned up my food. Then I sat down to write this paragraph. The rest of my breakdown would have to wait until work was done for the day.

Like 46 million Americans (according to the National Alliance on Mental Illness), I regularly deal with a mental illness that has the potential to disrupt my daily life. Some days it comes in the form of an emotional breakdown that stops everything I’m doing dead in its tracks. Most of the time, though, it is quieter. It can be a haze that makes work slow, or it can stifle ideas when I need them most.

Unlike many physical illnesses or disabilities, having a mental illness isn’t always visible to the people you work with.This can be a double-edged sword. On the one hand, it means you might not face as much open discrimination as someone with a more visible condition. On the other hand, when your mental illness makes doing your work difficult, to outsiders it can look as if you’re just not doing your job well, which also makes it hard to get the support you need.

Fortunately, United States law provides some protections for people with mental illnesses — just as they do for any physical disability — but they go only so far. Here, we’ll go over some of the support you can expect from your employer, but we’ll also discuss strategies you can use to get through the day, even when you’re not feeling your best.

The legal protections you have against discrimination

First and foremost, in most cases, you have the right under the Americans With Disabilities Act not to reveal that you suffer from any mental illness, so long as it doesn’t affect your ability to do your job. However, if you need special accommodations from your employer — some of which are also protected by the A.D.A. — you may need to disclose your condition.

One of your primary protections under the A.D.A. is that your employer cannot discriminate against you because of your condition. While employers have the right not to employ anyone they believe cannot perform the duties a job requires, they are not allowed to use the fact that you have a mental illness alone as a reason to discipline or terminate you. Notably, this extends to employers using stereotypes or misconceptions based on that mental illness.

For example, if you suffer from depression, and your employer — lacking a proper understanding of depression’s symptoms — incorrectly believes you would be too glum or sad to take care of customers, he or she wouldn’t be able to fire you or use it as a reason to withhold a promotion. This is a stereotype and not reflective of your actual job performance. If you received repeated complaints from customers about poor service or frequently failed to show up to work, however, your employer could use this as a reason for discipline or termination.

The reasonable accommodations you can ask for

The Equal Employment Opportunity Commission is the government agency charged with enforcing the A.D.A. and, according to the commission’s website, you have a right under the A.D.A. to accommodations for any condition that can “substantially limit” your ability to do your job if it is not addressed. Those accommodations include but may not be limited to:

Time off or flexible work schedules. If you need time off for therapy appointments or to take care of reasonable treatment, an employer must make a reasonable effort to work around your schedule. That doesn’t mean giving you as many days off as you want, but rather things like adjusting shifts around your appointments or providing sick days when your condition is worse.

A more accommodating work environment. If it is easier to get your work done with your condition when it is not loud, you can ask your employer for a quiet place to work, or accessories like headphones that let you work in peace.

Special supervisory conditions. Say you have a sensory issue that makes it difficult to retain verbal instructions: You can request that your employer submit instructions in writing instead.

Permission to work from home. You can request that your employer allow you to work from home, even in situations where other employees may not be granted the same opportunity. However, you must be able to perform your job duties remotely and keep up the level of work expected of you.

As you can imagine, the line between what counts as “reasonable” and not can become fuzzy. If having depression means you need to take a sick day every once in a while, that might be a reasonable accommodation to expect. If you frequently don’t show up to work without communicating with your employer, however, that would have a tangible impact on your job performance.

For some jobs, the accommodations you need might be entirely unavailable. You might be able to request a quiet work environment if you work in an office building. If you work on a construction site, however, that might be impossible. The key word is “reasonable,” and it’s a very fudgy word. As with a physical illness, you may be required to provide a doctor’s note or other documentation to your employer in order to get the accommodations you need.

It is also important that you ask for any accommodation you need before you’re in a situation where it could affect your work. If you don’t speak up about your needs and it affects your job performance, an employer can claim that your termination was because of your work, not your condition. It’s hard to argue if you never explained your situation or what you need in the first place.

What you can do when the law isn’t enough

In some cases, it is a good idea to talk to your employer to get accommodation. If you believe you’ve faced discrimination because of your condition, the E.E.O.C. is a good place to turn. As anyone who’s dealt with a mental illness on the job can tell you, however, the reality is often a lot messier than the law makes it seem.

Disclosing your condition to your employer can be scary. You may worry that this will define you in your employer’s eyes — and worse, you may be right. Sometimes bosses just don’t want to deal with helping struggling employees out. The law requires employers to make reasonable accommodations. It doesn’t require them to like it. Even compassionate bosses might not keep your condition in mind when making budgetary decisions or deciding who to promote.

With that in mind, there are a few strategies I’ve collected over the years that help balance personal needs with those of my employers:

Save the repetitive, tedious work for your down days. Some jobs may require both creative and mechanical or tedious work that you can split up and work on when you’re best able to do it. If your workweek includes brainstorming pitches for a meeting and manually entering data into a spreadsheet, try to get the more creative part of the job done when you’re having a good mental health day, and save the tedious stuff for when you’re having a harder time.

Seek out the work style that suits your needs best. For the last six years, I’ve had the good fortune to work from home. Before that, I learned that working in an office was harder for me based on my needs. You might prefer structure or you might prefer flexibility, but pursuing jobs that give you what you need can be better in the long term than trying to fit your needs into the spaces left over by your job.

Take care of your home life. You can’t control everything that happens at work. You have a lot more control at home. If you need space to cry, scream or break down, give it to yourself when you’re off the clock. Take care of the basic routines like food, hygiene and chores that give you a sense of stability.

Avoid trying to keep up with your co-workers. It’s easy to get swept up in a corporate culture that prioritizes a certain kind of performative work. If your co-workers can sit down for four straight hours and pump out work, don’t try to force yourself to do the same. If you need frequent breaks to keep your stress levels down, that’s how you work. As long as you’re able to do the job to your own (and your boss’s) satisfaction, how you get there shouldn’t be as big a factor.

The biggest lesson I’ve learned, however, is that there is no clear “right” way to do things. Sometimes what works is communicating with your boss about the specific steps you can take together to make a productive work environment for you. And sometimes it means giving yourself space to cry into your lunch for no good reason and coming back to your work when you’re ready. Both are valid and necessary.

Earlier this month (Sept 10), I saw an interesting headline on one of my newsfeeds:

“The Science Is Mixed on Taking Supplements for Mental Health, Research Review Finds”

Having studied the effect of supplements on mental wellness for more than 20 years, you can imagine that my curiosity was peaked?!?!

My highlights of the article appear below and the full article in the online magazine Gizmodo is here = https://gizmodo.com/the-science-is-mixed-on-taking-supplements-for-mental-h-1838014070

A new large review of the scientific evidence suggests that most dietary supplements don’t do much to help people suffering from mental health disorders.

(NOTE – if you actually read the full study – which I highlight for you below – you’ll see that “most dietary supplements” refers most often to studies of single-nutrient vitamins like folate – which you might expect is unlikely to have much benefit on its own against major depression?)

Supplements are often touted as something like a shortcut to a healthy body and mind, though evidence for that rosy view is lacking. Researchers in Australia took a deep dive into the medical literature to see what they could find about supplements and mental health.

Their review, published in the journal World Psychiatry, is a meta-analysis of 33 other meta-analyses published since 2012, which looked at randomized, controlled clinical trials of people taking supplements to treat symptoms of depression and other mental illnesses. All told, the trials included more than 10,000 patients, who often took the supplements alongside standard treatments. These supplements included vitamin B9, otherwise known as folic acid, omega 3 fatty acids, minerals like zinc or magnesium, and amino acids like N‐acetylcysteine (NAC) and glycine.

They ultimately found that supplements were safe to take and not likely to interfere with existing psychiatric medications. But many of the interventions tested, such as taking magnesium for depression or folic acid for schizophrenia, didn’t have significant evidence for their benefits. In other cases, such as taking NAC for depression symptoms, the evidence was positive but based on very small trials.

That said, there were situations where the positive evidence was compelling and merited further study, the authors said.

This was most apparent with taking omega-3s to supplement treatment for major depression; they might also have a small effect on relieving symptoms of ADHD. Some decent evidence showed that NAC could boost the benefits of standard treatments for mood disorders and schizophrenia. And there was also evidence that taking methylfolate—the byproduct of folic acid that our bodies actually use—could be useful as an add-on treatment for schizophrenia and depression. Methylfolate is already offered as a prescription medical food for people with treatment-resistant depression who are deficient in it.

“Although the majority of nutritional supplements assessed did not significantly improve mental health outcomes beyond control conditions, some of them did provide efficacious adjunctive treatment for specific mental disorders under certain conditions,” the authors wrote.

The findings, mixed as they are, should be seen in a positive light, according to study author Joseph Firth, a senior research fellow at Western Sydney University’s National Institute of Complementary Medicine.

“While there has been a longstanding interest in the use of nutrient supplements in the treatment of mental illness, the topic is often quite polarizing, and surrounded by either over-hyped claims or undue cynicism,” Firth said in a statement released by the university. “This mass of data has allowed us to investigate the benefits and safety of various different nutrients for mental health conditions—on a larger scale than what has ever been possible before.”

In addition to quantifying how effective some supplements can be for certain groups, Firth and his team said, there needs to be work done on figuring out why exactly they’re helpful.

People who have major depression, for instance, are sometimes deficient in methylfolate—often due to a genetic mutation that makes it hard for them to convert folic acid to methylfolate. Without enough methylfolate, these people are then less able to produce serotonin and other neurotransmitters important for proper mental functioning. There might very well be similar explanations for why the lack of certain nutrients is crucial to the development of mental illness in some people.

These explanations could also involve the gut microbiome—the teeming microbial environment that lines our digestive system. The gut has garnered more and more attention for its role in our physical and mental health in recent years, since it “talks” regularly with our brain. And many researchers now believe that the microbiome needs to be balanced for this line of communication to be healthy. For the time being, the authors noted though, there’s less evidence looking into whether probiotics and prebiotics—supplements loaded with “good bacteria”—can effectively help people with mental illness.

It’s also important to caution that anyone taking supplements should ideally consult their doctor first, since some can interfere with certain medications or medical tests. Experts generally recommend that people stick to single-ingredient supplements (rather than multivitamins), since those are less likely to contain useless, undisclosed, or potentially dangerous ingredients.

My highlights are below from the full research study in the journal World Psychiatry on which this article is based = https://onlinelibrary.wiley.com/doi/full/10.1002/wps.20672

The efficacy and safety of nutrient supplements in the treatment of mental disorders: a meta‐review of meta‐analyses of randomized controlled trials

Joseph Firth  Scott B. Teasdale  Kelly Allott  Dan Siskind Wolfgang Marx  Jack Cotter  Nicola Veronese Felipe Schuch  Lee Smith Marco Solmi  André F. Carvalho  Davy Vancampfort  Michael Berk Brendon Stubbs  Jerome Sarris

First published: 09 September 2019 https://doi.org/10.1002/wps.20672

Abstract

The role of nutrition in mental health is becoming increasingly acknowledged. Along with dietary intake, nutrition can also be obtained from “nutrient supplements”, such as polyunsaturated fatty acids (PUFAs), vitamins, minerals, antioxidants, amino acids and pre/probiotic supplements. Recently, a large number of meta‐analyses have emerged examining nutrient supplements in the treatment of mental disorders. To produce a meta‐review of this top‐tier evidence, we identified, synthesized and appraised all meta‐analyses of randomized controlled trials (RCTs) reporting on the efficacy and safety of nutrient supplements in common and severe mental disorders. Our systematic search identified 33 meta‐analyses of placebo‐controlled RCTs, with primary analyses including outcome data from 10,951 individuals. The strongest evidence was found for PUFAs (particularly as eicosapentaenoic acid) as an adjunctive treatment for depression. More nascent evidence suggested that PUFAs may also be beneficial for attention‐deficit/hyperactivity disorder, whereas there was no evidence for schizophrenia. Folate‐based supplements were widely researched as adjunctive treatments for depression and schizophrenia, with positive effects from RCTs of high‐dose methylfolate in major depressive disorder. There was emergent evidence for N‐acetylcysteine as a useful adjunctive treatment in mood disorders and schizophrenia. All nutrient supplements had good safety profiles, with no evidence of serious adverse effects or contraindications with psychiatric medications. In conclusion, clinicians should be informed of the nutrient supplements with established efficacy for certain conditions (such as eicosapentaenoic acid in depression), but also made aware of those currently lacking evidentiary support. Future research should aim to determine which individuals may benefit most from evidence‐based supplements, to further elucidate the underlying mechanisms.

Abundant evidence now suggests that people with mental disorders typically have an excess consumption of high‐fat and high‐sugar foods, alongside inadequate intake of nutrient‐dense foods, compared to the general population1-5. The relationship between poor diet and mental illness appears to persist even when controlling for other factors which could explain the association, such as social deprivation or obesity, and is not explained by reverse causation1, 6.

Furthermore, although the metabolic and hormonal side effects of psychotropic medications can affect food intake7, 8, inadequate nutrition appears to be present even prior to psychiatric diagnoses. For instance, in depression, it seems that poor diet precedes and acts as a risk factor for illness onset6, 9, 10. Similarly, in psychotic disorders, various nutritional deficits are evident even prior to antipsychotic treatment11.

The importance of diet for maintaining physical health is widely accepted, due to the clear impact of dietary risk factors on cardiometabolic diseases, cancer and premature mortality12, 13. In parallel, the potential impact of diet on mental disorders is increasingly acknowledged14, 15. However, along with regular food intake, nutrients can also be consumed in supplement form16. Supplements are typically used in attempts to: a) complement an inadequate diet (or low measured plasma levels of a nutrient) to achieve recommended nutrient intakes/levels; b) administer specific nutrients at greater doses than those found in a typical diet, for putative physiological benefits; c) provide nutrients in more bioavailable forms for individuals with genetic differences, or relevant health issues, which may result in poor nutrient absorption. Supplements can be synthetically manufactured or directly food‐derived, typically including substances such as vitamins (e.g., folic acid, vitamin D), dietary minerals (e.g., zinc, magnesium), pre/probiotics (from specific strains of gut bacteria), polyunsaturated fatty acids, PUFAs (typically as omega‐3 fish oils), or amino acids (e.g., N‐acetylcysteine, glycine).

Currently, there is an increased academic and clinical interest in the role of nutrient supplements for the treatment of various mental disorders14-16. This growth of research is partly attributable to our evolving understanding of the neurobiological underpinnings of mental illness, which implicates certain nutrients as a potential adjunctive treatment for a variety of reasons25.

First, recent clinical research has found that many mental disorders are associated with heightened levels of central and peripheral markers of oxidative stress and inflammation26-29, and an association has been reported between the efficacy of both pharmacological and lifestyle interventions for mental illness and changes in these biomarkers30, 31. Thus, the antioxidant and anti‐inflammatory properties of certain nutrient supplements (such as N‐acetylcysteine32 and omega‐3 fish oils33) indicates that these could be beneficial in the treatment of psychiatric conditions caused or exacerbated by heightened inflammation and oxidative stress.

Second, there are now extensive data from large‐scale studies showing that psychotic and mood disorders are associated with significantly reduced serum levels of essential nutrients, including zinc34, 35, folate36, 37 and vitamin D38, 39. Since these deficits appear to be related to treatment response and clinical outcomes in these populations11, 34, 40, there is a possibility that nutrient supplementation could improve outcomes.

Third, there is nascent (but growing) evidence that mental disorders may be linked to dysfunction of the gut microbiome41, 42. As gut bacteria can be modified through micronutrients and pre/probiotics43, 44, this suggests that some pre/probiotic supplements may serve as potentially useful novel therapeutic optionsworthy of further investigation45, 46.

DISCUSSION

The nutritional intervention with the strongest evidentiary support is omega‐3, in particular EPA. Multiple meta‐analyses have demonstrated that it has significant effects in people with depression, including high‐quality meta‐analyses with good confidence in findings as determined by AMSTAR‐264. Meta‐analytic data have shown that omega‐3 is effective when given adjunctively to antidepressants51, 64. As a monotherapy intervention, the data are less compelling for omega‐3, while DHA or DHA‐predominant formulas do not appear to show any obvious benefit in MDD51, 64.

Omega‐3 supplementation appears to be of greatest benefit when administered as high‐EPA formulas, as significant relationships between EPA dosage and effect sizes are also observed in high‐quality meta‐analyses of RCTs59, 64. Emergent data from RCTs further indicate that omega‐3 may be most beneficial for patients presenting with raised inflammatory markers83. The available meta‐analyses suggest that omega‐3 supplementation is not effective in patients with depression as a comorbidity to chronic physical conditions65, including cardiometabolic diseases, a finding which has been replicated in subsequent trials84. In light of current adverse event data, omega‐3 seems to represent a safe adjunctive treatment.

More research is needed concerning the efficacy of omega‐3 supplements in other mental health conditions. For instance, omega‐3 was indicated as potentially beneficial for children with ADHD, again with high EPA formulas conferring largest effects79. However, the negligible effect sizes after controlling for publication bias, along with the low review quality identified by AMSTAR‐2, reduces confidence in findings. Additionally, whereas the existing meta‐analytic data have found a lack of significant benefits in people with schizophrenia55, 59, subsequent trials in young people with first‐episode psychosis have reported more positive, though mixed, results85, 86, putatively ascribed to neuroprotective effects87, 88.

Adjunctive treatment with folate‐based supplements was found to significantly reduce symptoms of MDD and negative symptoms in schizophrenia54, 67. However, in both cases, AMSTAR‐2 ratings indicated low confidence in review findings, and positive overall effects in these meta‐analyses were driven largely by RCTs of high‐dose (15 mg/day) methylfolate. Methylfolate is readily absorbed, overcoming any genetic predispositions towards folic acid malabsorption, and successfully crossing the blood‐brain barrier89, 90. Indeed, a placebo‐controlled trial of methylfolate in schizophrenia reported significant increases in white matter within just 12 weeks, co‐occurring with a reduction in negative symptoms91.

Regarding other vitamins (such as vitamin E, C or D), minerals (zinc and magnesium) or inositol, there is currently a lack of compelling evidence supporting their efficacy for any mental disorder, although the emerging evidence concerning positive effects for vitamin D supplementation in major depression has to be mentioned.

N‐acetylcysteine may assist in treatment of schizophrenia, bipolar disorder and depression through decreasing oxidative stress and reducing glutamatergic dysfunction96, but has wider preclinical effects on mitochondria, apoptosis, neurogenesis and telomere lengthening of uncertain clinical significance.

The role of the gut microbiome in mental health is also a rapidly emerging field of research99. Gut microbiota differs significantly between people with mental disorders and healthy controls, and recent faecal transplant studies using germ‐free mice indicate that these differences could play a causal role in symptoms of mental illness41, 100, 101. Intervention trials that aim to investigate the effect of probiotic formulations on clinical outcomes in mental disorders are now beginning to emerge71. We included one recent meta‐analysis that evaluated the pooled effect of probiotic interventions on depressive symptoms: while the primary analysis reported no significant effect, the moderately large effect in the three included studies suggests that probiotics may be beneficial for those with a clinical diagnosis of depression rather than subclinical symptoms71. However, additional trials are required to replicate these results, to evaluate the long‐term safety of probiotic interventions, and to elucidate the optimal dosing regimen and the most effective prebiotic and probiotic strains102.

While improving dietary intake appears to have a clear role in increasing life expectancy and preventing chronic disease, there is currently a lack of studies evaluating this in people with mental disorders. Additionally, although recent meta‐analyses of RCTs have demonstrated that dietary improvement reduces symptoms of depression in the general population106, more well‐designed studies are needed to confirm the mental health benefits of dietary interventions for people with diagnosed psychiatric conditions25.

It is recognized that people with mental disorders commonly take nutritional supplements in combinations. In some instances, research has supported this approach, most commonly in the form of multivitamin/mineral combinations107. However, recent research in the area of depression has revealed that “more is not necessarily better” when it comes to complex formulations108. Of note, recent large mood disorder clinical trials have revealed that nutrient combinations may not have a more potent effect, and in some cases placebo has been more effective47, 108, 109.

In conclusion, there is now a vast body of research examining the efficacy of nutrient supplementation in people with mental disorders, with some nutrients now having demonstrated efficacy under specific conditions, and others with increasingly indicated potential. There is a great need to determine the mechanisms involved, along with examining the effects in specific populations such as young people and those in early stages of illness. A targeted approach is clearly warranted, which may manifest as biomarker‐guided treatment, based on key nutrient levels, inflammatory markers, and pharmacogenomics 83, 91, 110.

Have you ever wondered why Amare Global’s VitaGBX is so high in polyphenol-rich phytonutrients?

One reason is because they can help to protect delicate neurons (brain cells) from damage – and another is because they can help to improve blood flow to the brain, thus improving delivery of oxygen and nutrients for optimal brain performance.

But – did you also know that polyphenols can activate intracellular protection pathways like Nrf2 (to increase antioxidant enzyme production) AND inhibit inflammatory pathways like NF-KB (to reduce inflammatory cytokine production)?

This means that polyphenol-rich diets and supplements (like VitaGBX) have the potential to not just “protect” cells – but to help cells to actively “protect themselves” whenever they’re exposed to stress. No other multivitamin does what VitaGBX can do…

I though this recent paper (from 16 scientists in 7 countries) about NF-kB signaling by polyphenols was interesting? This research focuses on cancer, but the concept applies to any aspect of improved cellular protection – such as anti-aging effects.

Crit Rev Food Sci Nutr. 2019 Sep 12:1-11. Targeting NF-κB signaling pathway in cancer by dietary polyphenols.

Khan H1, Ullah H1, Castilho PCMF2, Gomila AS3,4, D’Onofrio G5, Filosa R6,7, Wang F8, Nabavi SM9, Daglia M10, Silva AS11,12, Rengasamy KRR13, Ou J14, Zou X15, Xiao J14,15, Cao H16.

Author information

• 1Department of Pharmacy, Abdul Wali Khan University , Mardan , Pakistan.
• 2CQM Madeira Chemistry Research Centre, Faculty of Exact Sciences and Engineering, Madeira University , Funchal , Portugal.
• 3Research Group on Community Nutrition and Oxidative Stress, University of the Balearic Islands , Palma de Mallorca , Spain.
• 4CIBEROBN (Physiopathology of Obesity and Nutrition, CB12/03/30038), Instituto de Salud Carlos III , Madrid , Spain.
• 5Department of Medical Sciences, IRCCS “Casa Sollievo della Sofferenza”, Complex Unit of Geriatrics , San Giovanni Rotondo , Italy.
• 6Department of Experimental Medicine, Università degli Studi della Campania Luigi Vanvitelli , Naples , Italy.
• 7Consorzio Sannio Tech , Apollosa , Italy.
• 8College of Food Science and Engineering, Nanjing University of Finance and Economics , Nanjing , China.
• 9Applied Biotechnology Research Center, Baqiyatallah University of Medical Sciences , Tehran , Iran.
• 10Department of Drug Sciences, Medicinal Chemistry and Pharmaceutical Technology Section, University of Pavia , Pavia , Italy.
• 11National Institute for Agricultural and Veterinary Research , Vairão , Vila do Conde , Portugal.
• 12Center for Study in Animal Science (CECA), ICETA, University of Oporto , Oporto , Portugal.
• 13Department of Bio-resources and Food Science, Konkuk University , Seoul , South Korea.
• 14Institute of Food Safety and Nutrition, Jinan University , Guangzhou , China.
• 15Institute of Food Safety and Nutrition, Jiangsu University , Zhenjiang , China.
• 16College of Food Science, Fujian Agriculture and Forestry University , Fuzhou , Fujian , China.

Abstract

Being a transcription factor, NF-κB regulates gene expressions involving cell survival and proliferation, drug resistance, metastasis, and angiogenesis. The activation of NF-κB plays a central role in the development of inflammation and cancer. Thus, the down-regulation of NF-κB may be an exciting target in prevention and treatment of cancer. NF-κB could act as a tumor activator or tumor suppressant decided by the site of action (organ). Polyphenols are widely distributed in plant species, consumption of which have been documented to negatively regulate the NF-κB signaling pathway. They depress the phosphorylation of kinases, inhibit NF-κB translocate into the nucleus as well as interfere interactions between NF-κB and DNA. Through inhibition of NF-κB, polyphenols downregulate inflammatory cascade, induce apoptosis and decrease cell proliferation and metastasis. This review highlights the anticancer effects of polyphenols on the basis of NF-κB signaling pathway regulation.

KEYWORDS:

Dietary polyphenols; cancer; nuclear factor-κB; phosphorylation; signaling pathway

Exciting press release about the Benioff’s donating $35-million to support microbiome research – see my highlights below and the original at = https://www.healio.com/gastroenterology/inflammatory-bowel-disease/news/online/%7B3bfd9729-7376-402c-aa93-8ac50d23faad%7D/ucsf-stanford-receive-35m-to-further-research-of-microbiome

UCSF, Stanford receive $35M to further research of microbiome

September 14, 2019

Marc Benioff, chairman and co-CEO of Salesforce, and his wife, Lynne Benioff, are donating $35 million to the University of California, San Francisco, and Stanford University to launch new research initiatives to develop microbe-based diagnostics and precision therapies, according to a press release.

“Lynne and I are honored to support the cutting-edge research of two of the world’s leading universities as they pioneer a new era of microbiome research, science and therapies,” Marc Benioff said in the release. “With a deeper understanding of the human microbiome, our generation can unlock new treatments that impact lives around the world.”

UCSF will receive $25 million and Stanford will receive $10 million to launch the UCSF Benioff Center for Microbiome Medicine and Stanford Microbiome Therapies Initiative.

“We are at a watershed moment in human biology — our health rests not only on the proper functioning of human genes, but also on the genes and products of our microbiome,” Susan Lynch, PhD, director of the UCSF Benioff Center for Microbiome Medicine, said in the release. “At UCSF, we are leveraging this knowledge and our exceptional community of faculty across campus to identify those at risk of disease and to develop tailored microbiome interventions to promote health.”

The goal of the newly launched center at UCSF is to find new ways to predict, prevent and treat disorders linked to microbiome dysfunction, including gastrointestinal conditions such as inflammatory bowel disease.

The initiative at Stanford, according to the release, will focus on developing microbial communities to create new microbiome-based therapies for testing in early-stage human clinical trials.

“The biggest opportunities and challenges in this area can be traced back to one thing — the microbiome has been impossible to study in a controlled way,” Michael Fischbach, PhD, director of the Stanford Microbiome Therapies Initiative (MITI), said in the release. “The discoveries that will stand the test of time, and will make a difference for patients, will come from building completely defined microbiomes and manipulating them precisely. The engineers and scientists in MITI are singularly focused on this goal and stand ready to invent any technology necessary to meet it.”

Seeking an Obesity Cure, Researchers Turn to the Gut Microbiome

The link between the gut and metabolic disease is a growing area of obesity research.

Good NY Times article from Sept 10 about the microbiome and obesity – see my highlights below and the full original at = https://www.nytimes.com/2019/09/10/well/eat/seeking-an-obesity-cure-researchers-turn-to-the-gut-microbiome.html

Especially interesting given that on Sept 5, I presented a snapshot of data from a new clinical pilot study showing how Amare Global’s Project b3 nutrition system can favorably modulate the microbiome and lead to dramatic improvements in metabolism (cholesterol/glucose), mood state (depression/anxiety/fatigue), and body fat percentage. A more complete data set will be presented at the upcoming International Society for Nutritional Psychiatry Research in London next month.

Dr. Elaine Yu, an endocrinologist at Massachusetts General Hospital in Boston, was inundated with volunteers when she put out a call a few years ago for overweight people who were willing to take part in a study of obesity and the microbiome.

People as far away as Alaska and Hawaii were eager to enroll. But the most surprising part was what they were willing to do. The study required them to swallow capsules containing stool to test whether gut bacteria from lean donors could improve their metabolic health.

“We had this concern that it would be difficult to recruit people because there’s a certain yuck factor with having to take a poop pill,” Dr. Yu said. “But we had an overwhelming number of volunteers wanting to participate.”

The link between the gut and metabolic disease is a growing area of obesity research. In recent years, scientists have uncovered clues that the microbiota, the community of trillions of microbes that live in the gut, plays a role in weight gain and metabolic disease. Now, in small studies, they are exploring whether they can spur changes in metabolism and potentially in body weight through a therapy known as fecal microbiota transplants, or F.M.T., which transfers gut bacteria from lean donors to the guts of obese patients.

The research, which is still in its infancy, has yielded mixed results and plenty of skepticism. Experts say fecal transplants will never replace diet, exercise, behavioral therapies and other standard interventions for obesity and Type 2 diabetes. But some believe they could lead to the discovery of bacteria that protect against metabolic disease, and perhaps become one of many tools that help obese patients who are struggling to shed pounds.

“Obesity is a very complex disorder,” said Dr. Jessica Allegretti, the director of the Fecal Microbiota Transplant Program at Brigham and Women’s Hospital. “Perhaps the microbiome is a contributing part of it, and maybe for everyone it’s slightly different. But even for patients where the microbiome is playing a big part, I think this would be something that is part of a larger weight loss program.”

Scientists have known for some time that the microbiomes of obese and lean people differ in striking ways.Obesity, insulin resistance and fatty liver disease are associated with less microbial diversity and higher levels of a group of organisms called Firmicutes. It is not clear whether the obesity and diseases come first or vice versa. But there are indications that the microbiome plays an important role.

Scientists have found differences in the gut bacteria of children as young as 6 months old that can predict future weight gain. Studies of obese mice show that they harbor gut microbes that are better able to harvest energy from food, and when their microbiota are transplanted into the guts of lean mice, the svelte recipients gain weight.

While these findings were coming to light, scientists discovered that fecal transplants were a remarkably effective treatment for Clostridium difficile, a devastating bacterial infection that often occurs when antibiotics decimate the healthy gut bacteria that keep it in check. Fecal transplants from healthy donors, administered through colonoscopy or capsules containing desiccated stool, reintroduce beneficial bacteria to the guts of ailing patients, providing resistance against C. difficile.

In at least one case described in a medical journal, a lean woman who received a fecal transplant from her overweight daughter to treat a C. diff infection quickly gained 34 pounds. Her doctors, however, said they could not be sure that the transplant fueled her sudden weight gain.

Dr. Purna Kashyap, head of the Gut Microbiome Laboratory at the Mayo Clinic, said that treating C. diff with a fecal transplant makes perfect sense because it dislodges a harmful pathogen and restores equilibrium to the gut. But obesity and metabolic disease are far more complex, driven by an array of factors, including genetics, diet, environment and lifestyle. The idea that a single intervention, a transplant of a new community of microbes, could effectively treat obesity is unrealistic, he said.

“The logic behind it falls apart,” he added. “It’s saying, because I don’t know what’s going on, let me just treat it with everything that I have and hope for the best.”

Some researchers nonetheless wondered what would happen if obese patients were given the gut microbes of slender people. The first direct test of this came in 2012. Dutch researchers showed that transferring a lean donor’s microbiota to the guts of obese men with metabolic syndrome led to a sharp increase in the recipients’ insulin sensitivity and their microbial diversity after six weeks, suggesting that the transplants influenced their metabolisms.

At Mass General, Dr. Yu and her colleagues recruited 24 obese men and women with insulin resistance, along with four lean donors. The donors were screened for an array of medical conditions to ensure that they were healthy and would not transmit any infections to the recipients. The researchers selected donors who had a history of always being very lean: Their ideal candidates were people who said they could eat whatever they wanted and still remain skinny.

“There could be many reasons why those people are special,” Dr. Yu said of the donors. “There could be genetic reasons that are unrelated to the microbiome. But we had to start somewhere.”

Half the obese subjects took specially prepared frozen capsules containing stool from the donors on a weekly basis, while the others received a placebo. After 12 weeks, the researchers found that the fecal treatment was safe and tolerable and that the subjects had acquired microbiota that resembled that of their skinny donors. But over all, unlike in the Dutch study, there was no improvement in their metabolic health. Like much of the microbiome research to date, both trials were small and exploratory and did not reach definitive conclusions.

Two other small studies led to some provocative findings. In one, at Brigham and Women’s Hospital, Dr. Allegretti found that fecal transplant capsules shifted the microbiomes of obese subjects and led to positive changes in their bile acids, digestive aids that are produced by the liver.

Another study in Canada looked at the effects of fecal transplants on liver fat in people with fatty liver disease. While the results are under peer review and awaiting publication, the authors said that the treatment led to changes in the recipients’ guts, making the gut membrane less permeable, or “leaky.”

This is important because one hypothesis for how an abnormal microbiome could contribute to metabolic disease and weight gain is by damaging the gut barrier that keeps toxins and pathogens from crossing into the bloodstream. When this occurs, it can set off a cascade of inflammation, contributing to insulin resistance, cardiovascular disease and autoimmune conditions, said Dr. Michael Silverman, the lead author of the study and the chairman of infectious diseases at Western University in Ontario.

None of the studies were long enough to assess changes in body weight. But some of the researchers plan to follow their subjects longer to gather more data on weight and other outcomes. Dr. Yu said that further research could help identify pathways that lead to new drugs or probiotics that alter the microbiome.

A clinical trial published in the journal Nature Medicine in July, for example, found that giving obese people supplements containing a gut microbe linked to leanness in mice and humans lowered their cholesterol, inflammation and insulin and even led to a few pounds of weight loss compared to a control group.

Still, Dr. Yu said a capsule containing a cocktail of beneficial microbes is never going to be a silver bullet.

“It would be great if there was a treatment that could come out of this research,” she added. “But I don’t think we’re going to find some magic potion that will be able to cure obesity in the absence of any other intervention.”