Recent Longevity News for the week ending 2/3/21

Metformin Could Help Prevent Some Breast Cancers - WebMD, 2/1/21 - "Compared to women without diabetes, risk for estrogen-positive breast cancer was 38% lower among women with type 2 diabetes who had used metformin for 10 years or more ... Metformin can improve insulin sensitivity and correct high insulin levels by reducing the amount of insulin and insulin-like growth factor circulating in the body, which may activate cell signals involved in cancer ... Metformin may also slow breast cancer growth by activating an enzyme called adenosine monophosphate activated protein kinase (AMPK) ... It blocks a pathway involved in spread of cancer cells ... Metformin has been hailed as something of a miracle for many diseases other than diabetes. Some research has linked it to a longer life span, reduced risk of vision loss and improved fertility in men and women." - See metformin at ReliableRX.

Newer iPhones Disable Implanted Defibrillators - Medscape, 2/1/21 - "Tests were performed on a patient wearing a Medtronic ICD ... "Once the iPhone was brought close to the ICD over the left chest area, immediate suspension of ICD therapies was noted," according to the authors of the study. The functional loss of the ICS persisted for the duration of proximity. It was reproduced multiple times and with multiple phone positions."

Bleeding gums may be a sign you need more vitamin C in your diet - Science Daily, 2/1/21 - "bleeding of the gums on gentle probing, or gingival bleeding tendency, and also bleeding in the eye, or retinal hemorrhaging, were associated with low vitamin C levels in the bloodstream. And, the researchers found that increasing daily intake of vitamin C in those people with low vitamin C plasma levels helped to reverse these bleeding issues ... both a gum bleeding tendency and retinal bleeding could be a sign of general trouble in one's microvascular system, of a microvascular bleeding tendency in the brain, heart and kidneys ... There was a time in the past when gingival bleeding was more generally considered to be a potential marker for a lack of vitamin C. But over time, that's been drowned out or marginalized by this overattention to treating the symptom of bleeding with brushing or flossing, rather than treating the cause" - See vitamin C products at Amazon.com.

Oily Fish Linked to Lower Risk of Diabetes in Largest Study to Date - Medscape, 2/1/21 - "Participants who ate either one, or two or more, servings of oily fish weekly each had a significant 22% lower rate of incident type 2 diabetes than those who ate no oily fish, after adjustment for multiple confounders. Those who reported regularly taking a fish oil supplement had a significant 9% lower incidence of type 2 diabetes than those who didn't ... Oily Fish: Solid Evidence for Prevention of CVD Events ... In contrast, the case for including oily fish in the diet to prevent CVD events seems settled. In 2018, a panel assembled by the American Heart Association to address the issue released a statement that concluded: "Current scientific evidence strongly supports the recommendation that seafood be an integral component of a heart-healthy dietary pattern." It added that "a large body of evidence supports the recommendation to consume nonfried seafood, especially species higher in long-chain n-3 fatty acids, one to two times per week for cardiovascular benefits, including reduced risk of cardiac death, coronary heart disease, and ischemic stroke."" - See omega-3 supplements at Amazon.com.

Serum Triiodothyronine-to-thyroxine (T3/T4) Ratio Predicts Therapeutic Outcome to Biological Therapies in Elderly IBD Patients - Medscape, 2/1/21 - "Baseline T3/T4 ratio was higher in patients with mucosal healing, as compared with those without mucosal healing (P < 0.0001), regardless of the disease type or biological drug (OR 6.4 [2.9–14.3] for each T3/T4 unit increase, P < 0.0001). A cut point of 3.3 was identified as the optimal threshold of baseline T3/T4 ratio for predicting mucosal healing, providing 78% sensitivity and 89% specificity (area under the ROC curve 0.88 [0.79–0.94]; positive and negative likelihood ratios 6.8 [2.9–15.9] and 0.3 [0.1–0.5] respectively) ... T3/T4 ratio seems a reliable tool for predicting therapeutic outcome of biological therapy in elderly patients with IBD"

Cannabis Tied to Self-Harm, Death in Youth With Mood Disorders - Medscape, 2/1/21 - "cannabis use disorder (CUD) .... the risk for self-harm was three times higher, all-cause mortality was 59% higher, unintentional overdose was 2.5 times higher, and homicide was more than three times higher in those with versus without CUD ... The take-home message of these findings is that we need to be aware of the perception that cannabis use is harmless, when it's actually not"

Frequent cannabis use by young people linked to decline in IQ - Science Daily, 1/28/21 - "The results revealed that there were declines of approximately 2 IQ points over time in those who use cannabis frequently compared to those who didn't use cannabis. Further analysis suggested that this decline in IQ points was primarily related to reduction in verbal IQ ... Previous research tells us that young people who use cannabis frequently have worse outcomes in life than their peers and are at increased risk for serious mental illnesses like schizophrenia. Loss of IQ points early in life could have significant effects on performance in school and college and later employment prospects"

Vitamin D Might Help Fight COVID-19 - WebMD, 1/28/21 - "Vitamin D is an essential nutrient, and recent research has suggested it may also help guard against severe COVID-19." - See vitamin D at Amazon.com.

Higher Dietary Fiber Tied to Lower Depression Risk in Young Women - Medscape, 1/28/21 - "the estimated mean dietary fiber intake was significantly higher in women without depression, compared with those with depression (14.07 ± .11 g/1000 kcal/d [95% CI, 13.85 - 14.29] vs 12.67 ± .45 g/1000 kcal/d [11.79 - 13.55]; P = .003) ... Although the relationship remained significant in premenopausal women, it lost significance in postmenopausal women ... The inverse relationship between dietary fiber intake and depression could be explained by the gut-brain interactions"

Melatonin is effective against polycystic kidney disease - Science Daily, 1/26/21 - "Though Gamberi says melatonin has not been previously used to treat PKD, she does think it holds some promise. PKD is a chronic disease, so treatment cannot include any toxic components. This rules out chemotherapy and tumour-killing antineoplastics used in oncology, for instance. However, melatonin is entirely non-toxic and shares certain properties with antineoplastics and anti-inflammatory agents." - See melatonin at Amazon.com.

What Anti Aging Supplements Should I Take? My Top 5 - 10 minute YouTube video.  He implies that he advises Elon Musk. I've already been taking all of them.

Exercising muscle combats chronic inflammation on its own - Science Daily, 1/22/21 - "Lots of processes are taking place throughout the human body during exercise, and it is difficult to tease apart which systems and cells are doing what inside an active person," said Nenad Bursac, professor of biomedical engineering at Duke. "Our engineered muscle platform is modular, meaning we can mix and match various types of cells and tissue components if we want to. But in this case, we discovered that the muscle cells were capable of taking anti-inflammatory actions all on their own."

NAD+ can restore age-related muscle deterioration, research finds - Science Daily, 1/20/21 - "Although aggregated proteins have been suggested to contribute to brain aging, this is the first time that they have been shown to contribute to muscle aging and to directly damage mitochondria. "These abnormal proteotoxic aggregates could serve as novel biomarkers for the aging process, beyond the brain and muscle," says Auwerx ... the researchers fed worms the vitamin nicotinamide riboside and the antitumor agent Olaparib, both of which boost the levels of nicotinamide adenine dinucleotide (NAD+), a biomolecule that is essential for maintaining mitochondrial function, and whose levels decline during aging ... The encouraging results led the researchers to test nicotinamide riboside in aged mice. The treatment also activated the mitochondrial defense systems and reduced the number and size of amyloid aggregates in different skeletal muscle tissues ... Drugs that boost mitochondrial quality control could therefore be tested in the clinic to reverse these age-related proteotoxic aggregates and rejuvenate tissues" - See nicotinamide riboside at Amazon.com.

Metformin Treatment Again Linked to Fewer Deaths From COVID-19 - Medscape, 1/20/21 - "Notably, the reduction in mortality among those with diabetes taking metformin prior to COVID-19 diagnosis was significant: 11% of those patients died compared with 23% of those with diabetes not taking metformin" - See metformin at ReliableRX.

Get a Good Night's Sleep Before Your COVID Vaccine - WebMD, 1/20/21 - "As COVID-19 vaccines are being distributed, it is of utmost importance that patients continue to prioritize their sleep to maintain optimal health ... Getting sufficient, high-quality sleep on a regular basis strengthens your body's immune system and optimizes your response to a vaccine ... A good night's sleep before and after vaccination could be very advantageous"

FDA Approval Adds Vericiguat (Verquvo) to HF Treatment Options - Medscape, 1/20/21 - "Vericiguat, which promotes vasodilation through stimulation of a nitric-oxide signaling enzyme pathway, was approved based primarily on the VICTORIA trial, which saw a 10% drop in adjusted risk for the primary end point, cardiovascular death, or first HF hospitalization (P = .019) in those who took the drug, compared with a placebo"

How dietary choice influences lifespan in fruit flies - Science  Daily, 1/19/21 - "It has been recognised for nearly a century that diet modulates aging ... Lyu and colleagues began by giving fruit flies either a diet of brewer's yeast and sugar mixed together, or a choice of the two nutrients separately. They found that having the choice between foods changed the flies' behaviour and metabolism, and shortened their lifespan, independent of how much they ate"

Go Low-Carb for Type 2 Diabetes Remission? - WebMD, 1/19/21 - "Overall, Brinkworth's team found, low-carb diets were winning at the six-month mark: People on those plans had lost, on average, about 7.5 pounds more than those on comparison diets, and their triglycerides (a type of blood fat) were lower ... In trials that looked at diabetes remission, 57% of people on low-carb plans had gone into remission, versus 31% of people on other diets. Remission meant that a person's average blood sugar in the past three months was below the threshold for diagnosing diabetes ... By the 12-month point, however, most of the advantages of low-carb diets had vanished ... "Despite the benefits for blood-sugar control that very low-carb diets can offer, they can be very difficult to adhere to," said Julie Stefanski"

Fried food intake linked to heightened serious heart disease and stroke risk - Science Daily, 1/18/21 - "they pooled the data from six, involving 754,873 participants and 85,906 deaths over an average monitoring period of 9.5 years, to assess the potential link between fried food consumption and deaths from cardiovascular disease and from any cause ... Their analysis showed that compared with the lowest category of weekly fried food consumption, the highest was associated with a 28% heightened risk of major cardiovascular events; a 22% heightened risk of coronary heart disease; and a 37% heightened risk of heart failure"

Fatty acid may help combat multiple sclerosis, study finds - Science Daily, 1/18/21 - "Fat tissue in patients diagnosed with MS lack normal levels of oleic acid, a monounsaturated fatty acid found at high levels in, for instance, cooking oils, meats (beef, chicken, and pork), cheese, nuts, sunflower seeds, eggs, pasta, milk, olives, and avocados, according to the study ... This lack of oleic acids leads to a loss of the metabolic sensors that activate T cells, that mediate the immune system's response to infectious disease, the Yale team found. Without the suppressing effects of these regulatory T cells, the immune system can attack healthy central nervous system cells and cause the vision loss, pain, lack of coordination and other debilitating symptoms of MS ... When researchers introduced oleic acids into the fatty tissue of MS patients in laboratory experiments, levels of regulatory T cells increased ... obesity triggers unhealthy levels of inflammation and is a known risk factor for MS, an observation that led him to study the role of diet in MS" - Note: Oleic acid is omega-9, like in olive and avocado oils.  Costco sells avocado mayonnaise.

Abstracts from this week:

Dietary lutein plus zeaxanthin and choline intake is interactively associated with cognitive flexibility in middle-adulthood in adults with overweight and obesity - Nutr Neurosci 2021 Jan 15 - "Among a sample of adults with overweight and obesity, greater intake of choline and lutein+zeaxanthin was associated with faster performance on a cognitive flexibility task. Future work examining methods of increasing consumption of both of these dietary components as a possible means of improving or maintaining cognitive flexibility among adults with overweight and obesity is therefore warranted." - [Nutra USA] - See citicholine at Amazon.com, lutein at Amazon.com and astaxanthin at Amazon.com.

Ten Days of Curcumin Supplementation Attenuates Subjective Soreness and Maintains Muscular Power Following Plyometric Exercise - J Diet Suppl 2021 Jan 22 - "Participants (n = 22; five females, 17 males) consumed either curcumin (500 mg) or placebo twice daily for 10 days (6 days pre, day of and 3 days post exercise) ... These data suggest curcumin reduces soreness and maintains muscular power following plyometric exercise" - [Nutra USA] - See curcumin at Amazon.com.

Efficacy and Safety of Tetrahydrocurcuminoids for the Treatment of Canker Sore and Gingivitis - Evid Based Complement Alternat Med 2020 Dec 16 - "Tetrahydrocurcuminoids (THCs) are among the major metabolites of curcuminoids with a higher bioavailability and physiological stability and exhibit a broad spectrum of therapeutic activities ... Patients were instructed to self-administer one chewable tablet containing 100 mg of THCs twice daily for up to 21 days ... THCs treatment significantly reduced the reddening at the site, difficulty in chewing, swallowing, and VAS pain score in the canker sore patients. Further, both single and multiple lesions were completely healed. In gingivitis patients, gingival appearance, bleeding, and inflammation were significantly reduced. No adverse effects were observed during the study" - [Nutra USA] - See curcumin at Amazon.com.

Maternal Intake of Lutein and Zeaxanthin during Pregnancy Is Positively Associated with Offspring Verbal Intelligence and Behavior Regulation in Mid-Childhood in the Project Viva Cohort - J Nutr 2021 Jan 20 - "Lutein and zeaxanthin are carotenoids associated with better cognition at older age ... Higher maternal L/Z intake during pregnancy was associated with better offspring verbal intelligence and behavior regulation ability in mid-childhood, suggesting a potential benefit during prenatal development. We did not find a benefit of higher maternal L/Z intake on other child cognitive or behavioral outcomes" - See lutein at Amazon.com and astaxanthin at Amazon.com.

Discovery of Natural Inhibitors of Cholinesterases from Hydrangea: In Vitro and In Silico Approaches - Nutrients 2021 Jan 17;13(1):254 - "Alzheimer's disease (AD) is a neurodegenerative disease conceptualized as a clinical-biological neurodegenerative construct where amyloid-beta pathophysiology is supposed to play a role. The loss of cognitive functions is mostly characterized by the rapid hydrolysis of acetylcholine by cholinesterases including acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Moreover, both enzymes are responsible for non-catalytic actions such as interacting with amyloid β peptide (Aβ) which further leads to promote senile plaque formation. In searching for a natural cholinesterase inhibitor, the present study focused on two isocoumarines from hydrangea, thunberginol C (TC) and hydrangenol 8-O-glucoside pentaacetate (HGP). Hydrangea-derived compounds were demonstrated to act as dual inhibitors of both AChE and BChE. Furthermore, the compounds exerted selective and non-competitive mode of inhibition via hydrophobic interaction with peripheral anionic site (PAS) of the enzymes. Overall results demonstrated that these natural hydrangea-derived compounds acted as selective dual inhibitors of AChE and BChE, which provides the possibility of potential source of new type of anti-cholinesterases with non-competitive binding property with PAS" - See Hydrangea supplements at Amazon.com.

Increased risk of dementia in hypothyroidism. A Danish nationwide register-based study - Clin Endocrinol (Oxf) 2021 Jan 22 - "Hypothyroidism is associated with increased risk of dementia. The association is influenced by co-morbidity and age. Every 6 months of elevated TSH increased the risk of dementia by 12%, suggesting that also the length of hypothyroidism influences the risk of dementia"

(-)-Epigallocatechin-3-gallate inhibits RANKL-induced osteoclastogenesis via downregulation of NFATc1 and suppression of HO-1-HMGB1-RAGE pathway - Biomed Res 2020;41(6):269-277 - "Osteoporosis disturbs the balance of bone metabolism, and excessive bone resorption causes a decrease in bone density, thus increasing the risk of fracture. (-)-Epigallocatechin-3-gallate (EGCG) is the most abundant catechin contained in green tea. EGCG has a variety of pharmacological activities ... EGCG upregulated heme oxygenase-1 (HO-1) and suppressed the extracellular release of high-mobility group box 1 (HMGB1). In addition, EGCG decreased the expression of the receptor for advanced glycation end products (RAGE), which is the receptor of HMGB1, in osteoclastogenesis. In summary, our study showed that EGCG could inhibit osteoclast differentiation through the downregulation of NFATc1 and the suppression of the HO-1-HMGB1-RAGE pathway. EGCG might have the potential to be a lead compound that suppresses bone resorption in the treatment of osteoporosis" - See epigallocatechin-3-gallate at Amazon.com.

The Impact of Statin Use prior to intensive Care Unit (icu) Admission on critically Ill Patients with sepsis -Pharmacotherapy 2021 Jan 22 - "length of stay (LOS) ... Among patients with sepsis admitted to the medical ICU, pre-ICU statin use is causally associated with a decrease in 30-day ICU mortality, ICU LOS, and 30-day in-hospital mortality compared to non-use. This study adds to the totality of evidence on the pleiotropic effect of statin use in patients with sepsis"

Mediterranean diet and antihypertensive drug use: a randomized controlled trial - J Hypertens 2021 Jan 25 - "Participants allocated to Mediterranean diet interventions were associated with lower risk of initiating antihypertensive therapy [5-year incidence rates: 47.1% in the control diet, 43.0% in MedDiets; hazard ratio = 0.84, 95% CI (0.74--0.97), in a model adjusted for age, sex, and recruitment site]. Volunteers using two drugs at baseline in the Mediterranean diet intervention enriched with extra-virgin olive oil decreased their risk of therapy escalation [5-year incidence rates: 22.9% in the control diet, 20.1% in the MedDiet; hazard ratio = 0.77, 95% CI (0.60--0.99)]. Allocation to Mediterranean diet interventions attenuated the association between antihypertensive therapy at baseline and incidence of major adverse cardiovascular events"

Antioxidant Activity of Docosahexaenoic Acid (DHA) and Its Regulatory Roles in Mitochondria - J Agric Food Chem 2021 Jan 26 - "Reactive oxygen species (ROS) are single-electron-bearing oxidation-reduction products that are mainly produced in mitochondria. Excessive ROS accumulation may lead to oxidative damage ... 100 μM DHA decreased cellular and mitochondrial ROS levels to 75.2 ± 9.4% (P < 0.05) and 55.1 ± 1.4% (P < 0.01), respectively. It also increased the total antioxidant capacity by 55.6 ± 0.1 and 49.2 ± 1.1% (P < 0.05), based on ABTS and FRAP assay results, respectively. Consistently, it increased the activities and gene expression of major antioxidant enzymes by at least 35 and 40% (P < 0.05), respectively. Furthermore, DHA promoted mitochondrial functions and biogenesis. These data suggested that DHA's antioxidant activity can be attributed to its enhancement of mitochondrial functions and biogenesis. This study may shed light on the molecular mechanisms underlying DHA's function in improving resistance to and relieving the symptoms of chronic disease" - See docosahexaenoic acid at Amazon.com.

Protection Mechanisms Underlying Oral Administration of Chlorogenic Acid against Cadmium-Induced Hepatorenal Injury Related to Regulating Intestinal Flora Balance - J Agric Food Chem 2021 Jan 26 - "Cadmium (Cd) is a heavy metal, which is widely used in the industry and daily life. It has a long half-life, so large amounts of Cd can accumulate in humans and become toxic. Chlorogenic acid (CGA) can eliminate free radicals and inhibit lipid peroxidation and is mainly used to prevent metal toxicity ... In acute Cd-exposed mice, CGA treatment (ip) alleviated Cd-induced oxidative damage and reduced the production of NO and MPO in the liver and kidney tissues, while TLR4 expression levels did not change significantly. After 8 weeks of Cd exposure, CGA administration (gavage) significantly alleviated gut dysbiosis by decreasing the Firmicutes to Bacteroidetes ratio, enhancing the relative abundances of bacteria, including Ruminiclostridium_9, Alloprevotella, and Rikenella, and inhibiting the activation of the TLR4/MyD88/NF-κB signaling pathway. These findings suggested that protection mechanisms underlying the oral administration of CGA against the Cd-induced hepatorenal injury was related to the regulation of the intestinal flora balance. CGA can be used as an effective component in daily diet to prevent Cd toxicity" - See chlorogenic acid at Amazon.com.

Effects of garlic supplementation on oxidative stress and antioxidative capacity biomarkers: A systematic review and meta-analysis of randomized controlled trials - Phytother Res 2021 Jan 23 - "Evidence suggests that garlic supplementation may have an effect on oxidative stress by augmenting the rate of enzymatic and non-enzymatic antioxidants and diminishing pro-oxidant enzymes ... Twelve randomized controlled trials (RCTs) were included. Garlic doses ranged from 80 to 4,000 mg/day, and intervention duration varied between 2 and 24 weeks. Garlic supplementation increased serum level of total antioxidant capacity (TAC) (Hedges' g: 2.77, 95% CI: 1.37 to 4.17, p < 0.001) and superoxide dismutase (SOD) (Hedges' g: 13.76, 95% CI: 4.24 to 23.29, p = 0.004), while it reduced the malondialdehyde serum level (MDA) (Hedges' g: -1.94, 95% CI: -3.17 to -0.70, p = 0.002). Due to limited data available, glutathione (GSH) was not considered for the current meta-analysis. The nonlinear dose-response effect of garlic supplementation was not observed with regard to serum TAC and MDA levels (TAC: p-nonlinearity = 0.398; MDA: p-nonlinearity = 0.488). Garlic supplementation appears to improve serum levels of TAC, MDA, and SOD. Garlic supplementation may be useful to reduce oxidative stress and related diseases" - See garlic supplements at Amazon.com.

Anti-Inflammatory Effects of Quercetin on High-Glucose and Pro-Inflammatory Cytokine Challenged Vascular Endothelial Cell Metabolism - Mol Nutr Food Res 2021 Jan 22 - "Pro-inflammatory stimuli such as hyperglycemia and cytokines have been shown to negatively affect endothelial cell functions ... human umbilical vein endothelial cell (HUVEC) metabolites ... Treatment of HUVECs with high-glucose concentrations causes significant increases in lactate and glutamate concentrations. Quercetin inhibits glucose-induced increases in lactate and adenosine 5'-triphosphate (ATP) and also increased inosine concentrations. Tumor necrosis factor α-treatment (TNFα) of HUVECs causes increases in asparagine and decreases in aspartate concentrations. Co-treatment with quercetin reduces pyruvate concentrations compared to TNFα-only treated controls. Subsequently, it was shown that quercetin and its HUVEC phase-2 conjugates inhibit adenosine deaminase, xanthine oxidase and 5'nucleotidase (CD73) but not ectonucleoside triphosphate diphosphohydrolase-1 (CD39) or purine nucleoside phosphorylase activities ... Quercetin was shown to alter the balance of HUVEC metabolites towards a less inflamed phenotype, both alone and in the presence of pro-inflammatory stimuli. These changes are consistent with the inhibition of particular enzymes involved in purine metabolism by quercetin and its HUVEC metabolites" - See quercetin at Amazon.com.

Impact of Serum 25(OH) Vitamin D Level on Mortality in Patients with COVID-19 in Turkey - J Nutr Health Aging 2021;25(2):189-196 - "Patients were stratified into different vitamin D groups; Normal (Serum 25(OH) vitamin D level >30 ng/mL), Vitamin D insufficiency (21-29 ng/mL), and deficiency (<20 ng/mL) ... Mean serum 25(OH) vitamin D level was significantly lower in patients with severe-critical COVID-19 compared with moderate COVID-19 (10.1 ± 6.2 vs. 26.3 ± 8.4 ng/mL, respectively, p<0.001). Vitamin D insufficiency was present in 93.1% of the patients with severe-critical COVID-19 ... Serum 25(OH) vitamin D was independently associated with mortality in COVID-19 patients" - See vitamin D at Amazon.com.

Vitamin D Deficiency and Low Serum Calcium as Predictors of Poor Prognosis in Patients with Severe COVID-19 - J Am Coll Nutr 2021 Jan 12 - "Hypovitaminosis D and hypocalcemia were very common, occurring in 75% and 35.8% of patients. When analyzing survival, both were significantly associated with in-hospital mortality in a dose-effect manner (pLog-Rank = 0.009 and 0.001 respectively). A cutoff value of 39 nmol/l for vitamin D and 2.05 mmol/l for corrected calcemia could predict poor prognosis with a sensitivity of 76% and 84%, and a specificity of 69% and 60% respectively. Hazard ratios were (HR = 6.9, 95% CI [2.0-24.1], p = 0.002 and HR = 6.2, 95% CI [2.1-18.3], p = 0.001) respectively" - See vitamin D at Amazon.com.

The role of SGLT-2 inhibitors in managing type 2 diabetes - Cleve Clin J Med 2020 Dec 31 - "Sodium-glucose cotransporter-2 (SGLT-2) inhibitors are an exceptionally versatile class of medication, and their glycemic and nonglycemic benefits could help millions of patients with type 2 diabetes. Of note, they have been shown to improve cardiac and renal outcomes, much-needed benefits in patients with type 2 diabetes, who are at a higher risk for developing cardiac and renal dysfunction than those who do not have diabetes. The indications for SGLT-2 inhibitors may continue to expand as ongoing clinical trials provide more insight into these drugs"

The Effects of Vitamin E, Silymarin and Carnitine on the Metabolic Abnormalities Associated with Nonalcoholic Liver Disease - J Diet Suppl 2021 Jan 25 - "Studies indicate that antioxidant supplementation may improve abnormal liver chemistries, glucose control, and hyperlipidemia, in patients with nonalcoholic fatty liver disease (NAFLD). The primary objective of the study was to determine the normalization of abnormalities in hepatic function testing in patients with NAFLD when treated with vitamin E 200 IU, Silymarin 750 mg, and l-carnitine 1 gram (VSC) for 18 weeks in comparison to a placebo-controlled group ... VSC caused a significant reduction in serum glucose, insulin, and HOMA levels. While there were downtrends in the other measured values these were not statistically significant. In this 18-week study, the ability of this supplement in reducing markers of liver inflammation, glucose, insulin, and triglycerides indicate that this supplement could play an important role in the treatment of nonalcoholic fatty liver disease, diabetes, and the metabolic syndrome" - See Jarrow FamilE (contains all eight members of the vitamin E family, includes Tocomin) at Amazon.com, silymarin at Amazon.com and l-carnitine at Amazon.com.

I was searching for something to lower SHBG and ran across this:

• Effect of Tongkat Ali on stress hormones and psychological mood state in moderately stressed subjects - J Int Soc Sports Nutr. 2013; 10: 28 - "The effects of tongkat ali in restoring normal testosterone levels appears to be less due to actually “stimulating” testosterone synthesis, but rather by increasing the release rate of “free” testosterone from its binding hormone, sex-hormone-binding-globulin (SHBG) [17,18]. In this way, eurycoma may be considered not so much a testosterone “booster” (such as an anabolic steroid), but rather a “maintainer” of normal testosterone levels and a “restorer” of normal testosterone levels (from “low” back “up” to normal ranges) [19]. This would make eurycoma particularly beneficial for individuals with sub-normal testosterone levels, including those who are dieting for weight loss, middle-aged individuals suffering with fatigue or depression, and intensely training athletes who may be at risk for overtraining ... Salivary cortisol levels were significantly lower (−16% compared to placebo, PL) following tongkat ali (TA) supplementation (200 mg/day for 4 weeks) ... Daily supplementation (200 mg/day for 4 weeks) with tongkat ali (TA) resulted in significant improvements compared to placebo (PL) for indices of Tension (−11%), Anger (−12%), and Confusion (−15%) in moderately stressed adults ... Tongkat ali has been referred to as Malaysia’s “home-grown Viagra” [4] with the Malaysian government investing considerable effort to license, develop, and sustain research into the potential health benefits of Eurycoma longifolia through a variety of governmental organizations, including the Forest Research Institute of Malaysia" - See tongkat at Amazon.com.
• Men’s Sexual Health: Testosterone & Nitric Oxide Modulation - Huntington University of Health Sciences - "it is significant to note that the human clinical research has been done on a specific proprietary extract known as LJ100. This is important since the LJ100 extract of E. longifolia has been standardized for ... eurypeptides, naturally-occurring compounds which may be the active phytochemicals in E. longifolia, or at least serve as a marker for extract quality ... Human clinical studies on LJ100 have ... been conducted at different dosage levels, but 200 mg/day showed the most benefits. Studies included both controlled trials and open-label trials. It will not be possible to provide a detailed review all of the studies; however, here ...is a synopsis of the research results: Depending on the study, T increased 16.4-71.5 percent 11-13 ... Depending on the study, cortisol decreased 16-32 percent14,11 ... DHEA increased 47 percent9 ... Sexual health scores improved significantly10,15, as much as 91 percent9 ... It appears that at least one of the mechanisms of action for LJ100 is the reduction of sex hormone-binding globulin (SHBG) levels. SHBG is a glycoprotein that binds to sex hormones. While bound to SHBG, T cannot bind to cellular androgen receptors—which means that it won’t have any of the valuable effects of T in this form. Of course, SHBG-bound T can be unbound, but it can take a while for this to happen. Furthermore, SHBG levels increase as we age.2 In one of the studies, LJ100 was shown to reduce SHBG levels in 36 percent of the cases after one week, and 66 percent after three weeks" - See LJ100 at Amazon.com.
• Male Hormonal Health and the Role of Eurycoma longifolia Herb in Enhancing Free Testosterone in Ageing Men - Rainforest Herbs, 8/13/17 - "In their follow-up study the effects of Tongkat Ali extract on testosterone, dehydroepiandrosterone (DHEA) and sex hormone binding globulin (SHBG) were investigated over a 3 week period using an intermediate dosage of 50 mg extract capsules, with 4 capsules taken each day. Also a questionnaire to determine improvement in quality of life and sexual response was given to the participants. The final results showed that 82% of the participants experienced improvements in physical, sexual and psychological well-being. While total testosterone was not significantly different, the DHEA levels had increased by 26% after one week to 47% after 3 weeks. SHBG levels had reduced in 66% of cases after 3 weeks. When SHBG decreases the free testosterone index (FTI) increases. The FTI analysis showed an increase in 39% of participants after 1 week and 73% of participants after 3 weeks."

Potential use of ubiquinol and d-ribose in patients with heart failure with preserved ejection fraction - Annals of Medicine and Surgery, Volume 55, July 2020, Pages 77-80 - "HFpEF is a common and often debilitating disease process that may be difficult to diagnose and has limited targeted therapeutic options. Mitochondrial dysfunction appears to play a significant role in the pathophysiologic processes of this clinical syndrome. Improved methods of diagnosis for HFpEF are needed, as are specific effective therapies. Active ongoing research into the roles of ubiquinol and d-ribose in HFpEF may provide clinicians with additional management opportunities" - [Nutra USA] - See D-ribose at Amazon.com and ubiquinol products at Amazon.com.

Neat Tech Stuff / "How To's":

My last three bills have been up $200. I found the culprit. The way I was able to figure it out was that I installed a Moen Flo ( https://amzn.to/3pYF78L ). Then I turned off all the other toilets, the water softener and the reverse osmosis except for our boarder's toilet. Using the real-time graph, there was still a one-gallon dump exactly every five minutes. You could not see that it was leaking by looking at it. When I tied the lever up on that toilet, it stopped. Moen has a referral link that gets you 20% off. Here’s the link: http://fbuy.me/v/ben_4629

Getting the pipes to align with the valve was difficult.  If I did it again I'd use a flexible pipe on the outlet side such as this: https://amzn.to/3o3hdaL .  Home Depot doesn't stock the one-inch size.

Real-time graph	Installed valve
Before/After after I found the leak

Health Focus (C-reactive protein):