Metformin Enhances Autophagy and Normalizes Mitochondrial Function to Alleviate Aging-Associated Inflammation

[Mito]

Highlights​

• CD4+ T cells from healthy older people preferentially produce a Th17 profile
• Autophagy, but not mitophagy, knockdown activates a Th17 profile in “young” cells
• Mitochondrial ROS is needed, but not sufficient, for a Th17 profile in “young” cells
• Metformin improves autophagy and mitochondria in parallel to decrease inflammaging

Summary​

Age is a non-modifiable risk factor for the inflammation that underlies age-associated diseases; thus, anti-inflammaging drugs hold promise for increasing health span. Cytokine profiling and bioinformatic analyses showed that Th17 cytokine production differentiates CD4+ T cells from lean, normoglycemic older and younger subjects, and mimics a diabetes-associated Th17 profile. T cells from older compared to younger subjects also had defects in autophagy and mitochondrial bioenergetics that associate with redox imbalance. Metformin ameliorated the Th17 inflammaging profile by increasing autophagy and improving mitochondrial bioenergetics. By contrast, autophagy-targeting siRNA disrupted redox balance in T cells from young subjects and activated the Th17 profile by activating the Th17 master regulator, STAT3, which in turn bound IL-17A and F promoters. Mitophagy-targeting siRNA failed to activate the Th17 profile. We conclude that metformin improves autophagy and mitochondrial function largely in parallel to ameliorate a newly defined inflammaging profile that echoes inflammation in diabetes.

https://www.cell.com/cell-metabolism/fulltext/S1550-4131(20)30197-2

 

[aliml]

Factors that May Lower An Elevated Th17 Immune System - SelfHacked

Th17 cells produce inflammatory cytokines like IL-17 and TNF-alpha. Learn what foods & lifestyle choices affect this response.

selfhacked.com

Th17 cells produce inflammatory cytokines like IL-17 and TNF-alpha.

What are T Helper Cells 17 (Th17) and Interleukin-17?​

Reconciling Th1/Th2 Discrepancies​

You’ve probably heard about the Th1 and Th2 response. To rewind, the Th1/Th2 theory is one attempt at understanding immune regulation, and Th1 and Th2 cells are its key players.
This theory dates back to studies on mouse immune cells in the 80s. However, it is still considered controversial and it’s not without limitations and discrepancies [1].
According to the Th1/Th2 theory [1]:

• Th1 cells drive the so-called type-1 pathway (“cellular immunity”). They are thought to be involved in fighting viruses and other pathogens that enter cells, getting rid of cancerous cells, and triggering delayed-type hypersensitivity (DTH) skin reactions.
• Th2 cells drive the type-2 pathway (“humoral immunity”). They are hypothesized to increase antibody production and fight invaders that are outside cells. They may be involved in tolerance of organ transplants (xenografts) and of the fetus during pregnancy

But the human immune system is incredibly complex. We have many other types of immune cells that are orchestrated by various factors — from our encounter with microbes, to our health status, genetics, mood, and more.
That’s where Th17 cells come in. These cells were identified only recently and scientists think they can fill the missing gaps and explain some inconsistencies with the Th1/Th2 theory [2].
For example, Th17 cells are implicated in several human diseases and their cytokines are linked to inflammation and tissue damage [2].
In turned out that about a third of the progenitors — T helper cells — develop into Th17 cells, a third into Th1, and a third into Th2 cells [2].
However, Th17 science is new and the findings so far have been inconclusive. Let’s take a look at how much we know about this newly-discovered immune pattern.

Overview​

T helper cells start off as “naive” T cells and can turn into Th1, Th2, or Th17 cells.
A naive T cell can either become an inflammatory Th17 cell or an anti-inflammatory Treg cell. According to some researchers, the goal in inflammation is to convert more Th17 cells to Treg cells [2].
Cytokines or the lack of them influence which cell the naive helper cell will convert into. The two necessary cytokines are TGFb and IL-6, which we’ve spoken about [3].
Scientists claim that IL-6 (some say IL-21) is what ultimately determines if it turns into an inflammatory or anti-inflammatory cell. IL-23 is a cytokine that may determine if these Th17 will cause disease, though more research is needed [3].
IL-1β can also increase the production of Th17 cells [4].Th17 cells produce the cytokine IL-17, as well as TNF and others [5].

Link to Kynurenine​

Kynurenine is a metabolite of the amino acid tryptophan, used by the body while producing niacin. Recently, this pathway has been linked with everything from inflammation to immune imbalances and brain disorders [6].
Studies are still trying to decipher its impact on disease and whether it can be a therapeutic target [6].
Scientists think that IL-17 increases kynurenine (so does cortisol, IL-1, TNF, and IFNy/Th1 dominance) [7].
Limited data linked IL-17 to IBS [8]. However, the effects of increasing this pathway are mixed. Some animal studies suggest that it increases oxidative stress and may be associated with low mood [9].
Kynurenine can turn into kynurenic acid or quinolinic acid. Kynurenic acid blocks NMDA, AMPA, glutamate and nicotinic receptors, all of which are important for learning and memory.
Thus, some scientists hypothesize that kynurenic acid can reduce intelligence [10]. On the other hand, inhibiting Kynurenic acid seems to result in cognitive enhancement in mice [11]. Although intriguing, human data are needed.

Other Pathways​

Interleukin 17 acts antagonistically with TNF and IL-1 [12] (antagonism is the opposite of synergy).
In some studies, IL-17 was associated with allergic responses. Researchers found that it induces the production of other inflammatory compounds (such as IL-6, IL-1β, TGF-β, TNF, IL-8, MCP-1, and PGE2) that is thought to lead to negative events like airway narrowing in people with asthma [12].
Th17 cells seem to have a circadian rhythm. The amount of Th17 cells changes during the day-night cycle. Animal studies suggest that the production of Th17 is higher at midnight than at noon [13].
Science reminds us that Th17 and IL-17 aren’t just “bad,” though.
Based mostly on animal findings, Th17 appears to have a protective role in combating fungi [14] and some bacterial infections (“extracellular”) [15], along with Tregs [15].
Researchers are investigating whether Th17 may have anticancer properties, but studies are still in the early phases. Other scientists speak of the “cancer and autoimmune trade-off,” but this theory is still filled with inconsistencies, leaving us with more questions than answers [16].
Additionally, Th17 cells appear to be resistant to the suppressive effects of Tregs [17, 18].
Studies in animal models of MS suggest that Th1 cells are important in initiating acute attacks, while Th17 cells are hypothesized to be more important in mediating the progression of this disease. This hasn’t been confirmed in humans, but one study found higher IL-17 expression in chronic versus acute MS lesions [19].
Limited data suggest that in people with food allergies (classical type), IL-17 production was impaired, but not in healthy people. The study found IL-17 was a potential biomarker for tolerance to food antigens. Large-scale studies are needed [20].
A normal range of IL-17A has yet to be defined. One study proposed levels of 0.89 pg/ml. In people with mild sleep apnea, levels are 1.02 pg/ml, in moderate sleep apnea 1.18 pg/ml, and in severe sleep apnea 1.62 pg/ml. (all median values). More research is needed [21].

Gender Differences​

Studies suggest that women are more susceptible than men to autoimmune conditions, including Multiple Sclerosis (female to male ratio of 2:1), Rheumatoid Arthritis (2:1), Systemic Lupus Erythematosus (9:1), Sjogren’s syndrome (9:1), and Hashimoto’s thyroiditis (9:1) [19].
The higher female prevalence of these diseases may be related to the fact that women might develop more robust immune responses than men [19].
Limited studies have suggested that men are more prone to Th17 and Th2 dominance, while women are thought to be more prone to Th1 dominance. However, there’s no hard evidence to back this up [22, 19].
For example, one study found that women have higher levels of Th1 cells, IgM, and CD4+ cell counts, and show stronger immune response responses to vaccinations. Other studies had mixed findings [19].
Additionally, studies indicate that pregnancy is a Th2 state. Scientists think that lower Th1 activity is part of the adaptive physiological response that women go through in pregnancy [1].
This is said to prevent the mother’s antibodies from mounting an attack against the fetus. It’s also thought to explain why women are more prone to infections during pregnancy. Many women with rheumatoid arthritis — typically seen as a Th1 disease — experience relapses after pregnancy [1].
On the other hand, male sex hormones or androgens may increase PPAR alpha, which causes inhibition of Th1 dominance in animals. At the same time, men tend to have lower PPAR gamma, which is hypothesized to lead to Th17 dominance [22].
To some extent, researchers believe that Th1 and Th17 “compete” with each other, but this is also uncertain. Some studies indicate that IL-2 produced by Th1 cells activates STAT5, which competes with STAT3 (thought to be produced in Th17 dominance) [22].
In line with this, the castration of male mice enhances Th1 autoimmunity and lowers Th2 cytokine production. We can’t extrapolate these findings to humans [19].

Diseases Associated With Increased Th17​

The majority of studies covered in this section deal with associations only, which means that a cause-and-effect relationship hasn’t been established.
For example, just because autoimmune diseases have been linked with increased Th17 activity doesn’t mean that and autoimmunity is caused by Th17 dominance. Data are lacking to make such claims.
Also, even if a study did find that Th17 activity contributes to autoimmune diseases, Th17 cells are highly unlikely to be the only causative factor. Complex autoimmune disorders always involve multiple possible factors – including biochemistry, environment, health status, and genetics – that may vary from one person to another.
Additionally, some of the studies listed below rely on animal experiments, which can’t be applied to humans. More research is needed before we understand how Th17 cells affect health in humans.

• Several Autoimmune diseases: Hashimoto’s [23], Grave’s [24], Multiple Sclerosis [25], Lupus/SLE [26], Uveitis [27], Type 1 diabetes [28], Systemic Sclerosis [29], Autoimmune myocarditis [29], Vitiligo [30]
• Heart disease [31, 32] (IL-17) – contradictory [26]
• IBS [33] – some cases
• Rheumatoid arthritis [34, 29]
• Hashimoto’s [35], Graves [35]
• Multiple Sclerosis [25]
• Asthma [36], Airway inflammation [37]
• IBD [29]: Crohn’s [38], Colitis [39]
• Sleep apnea [40, 21]
• Skin: Acne Lesions [41], Psoriasis [29], Eczema[42]
• Some cancers (extremely limited data) [43]
• Fibromyalgia [44] – increased IL-17A
• Osteoporosis in menopausal women [45, 46]
• Depression [47] (IL17 and TGFbeta1) [48]
• Periodontal Disease [29]
• Lyme arthritis. Lyme or B. burgdorferi seems to increase IL-6, IL-1b, IL-23, and TGFb, which increases Th17 immunity and may trigger Lyme arthritis [49].
• Stroke damage (IL-17) [50]

Th17 overactivity is hypothesized to lead to infertility in women because the Th17 response makes the immune system attack sperm [51].
On the other hand, Estradiol (E2) inhibits Th17 cell responses, so that sperm is not attacked during ovulation. Some scientists say this sheds light on the connection between fungal infections (which increase Th17) and female infertility, but proper data are lacking to back up this whole Th17-infertility theory [51].
Th17 is lower in chronic fatigue syndrome. A cause-and-effect relationship hasn’t been established [52].

Exceptions to the Rule​

The Th1/Th2 theory states that overactivation of either the Th1 or the Th2 pattern can cause disease. Similarly, either pathway is thought to down-regulate the other [1].
Based on this, some studies claim that most substances that decrease Th1 will increase Th2 and vice versa (decreasing Th2 will increase Th1), but this isn’t always the case.
To expand this theory, substances that inhibit Th1 cells are usually thought to also inhibit Th17 cells. But as usual, there are some exceptions.
For example, Lithium only inhibits Th1 but not Th17 in cells and mice [53].
IL-17 is one of the main cytokines released by Th17 cells. Theoretically, inhibiting this cytokine blocks damage caused by these cells, but this still hasn’t been proven in humans.
There are two proteins that allow the cytokine IL-17 to be produced: STAT3 and Nf-kB [54]. We discuss factors that inhibit Nf-kB in this article. Below, we’ll dive into the research behind STAT3 inhibition.

Factors that May Balance Immunity (Inhibit Th17 and IL-17)​

Lifestyle​

• Reduce stress [55]
• Sun/UV Exposure [56] and Nitric Oxide [57] – but not Th1
• Exercise [58]
• Keeping a Circadian Rhythm [59]
• Cold Acclimation [60]

Diet​

• Avoid lectins [61]
• Fish oil [62] (reduced the surface expression of both IL-6R and IL-23R)
• Broccoli sprouts/Sulforaphane [63]
• One meal per day (in response to LPS) [64]
• Coffee [65]
• Kombucha/Lactic acid [66] (but they may increase IL-17A)

Nutrients​

• Vitamin A/Retinol [67, 68] (RAR alpha)
• Zinc [69], (STAT3-)
• Vitamin D3 [70], (via increasing C/EBP homologous protein)
• Potassium [71]
• Folate [72] (deficiency caused Treg cells reduction in animals)
• Chromium [73]

Supplements​

• Probiotics: L. salivarius [74], L. plantarum [74]
• Curcumin [75] – IL23, IL17 [76]
• Berberine [77]
• EGCG [78]
• Ursolic acid [79]
• Andrographolide [80]
• Black Cumin Seed Oil
• Olive leaf extract [81, 82]
• Fisetin [83] (inhibits IL-17)
• Chinese Skullcap/Baicalin [84, 85] (Number of Th17 and IL-17)
• NAG [86]
• Red Yeast Rice/statins [20] – synergizes with corticosteroids
• Grape Seed Extract [87, 88] (STAT3-)
• Boswellia [89]
• R-Lipoic Acid [90]
• Epimedium/Icariin [91]
• Apigenin [92]
• Honokiol [93]
• CBD [94]
• Galantamine [95, 96, 97]
• Huperzine A [95]
• Butyrate [98] – but increases it in response to an infection [99]
• Cinnamon/NaB [100] (increases IL-17)
• Artemisinin [101]
• Beta-Caryophyllene [102]
• Resveratrol* [103, 104] (conflicting)
• Probiotics: Enterococcus faecalis [105], (Mice)
• Parthenolide [106] – IL-17A [107]
• Ancient Wheat [82]
• Licorice/Lico A [108] (uncertain) [109]
• Ginger extract [110]

Hormones and Neurotransmitters​

• Estradiol/Estrogen [51]
• Progesterone [111, 112]
• Melatonin [113]
• TRH [114]
• GABA(A) [115]

Drugs​

• Aspirin [116]
• Methotrexate (drug) [117]
• Metformin [118]
• THC [119]
• Nicotine [95, 96, 97]

Pathways​

Scientists are investigating whether the following pathways reduce Th17 patterns in animals and cells:

• CB2 Receptor activation [120]
• PPAR delta [121]
• PPARgamma [122]
• Vitamin D receptor [68]
• RAR alpha [68]
• LXR [123]
• DRD5 (-) [124]
• STAT3 (-) [69]
• STAT1 (-) [91]
• HDAC (-) [125]
• IDO (+) [126]
• DPP4 (-) [127]
• mTORC1 [128]
• Acetylcholinesterase (-) [95]
• Cyp11a1 (-)
• RORyt (-)
• HIF1a (+) [129]
• AKT(-) [130]
• Dopamine d1R(-)… (inducible)… mTORC2(-) (natural)
• IL-1b (-) [89] – central role [131]
• IL-6 (-) [132] – central role [131]
• IL-23 (-) [132] – central role [131]
• TGF-b (-)
• H4R (-) [133]
• NF-kB (-) [67]
• GSK3 (-) [134]
• IL-17 (-) [135]
• IL-21 (-) [131]
• IL-10 (+)
• TNF (-) [131]
• IFN-b [136]
• IFNy [137]
• IL-12 [138]
• IL4 [138]
• PGE2 (-) [139]
• CD5 (-) [140]

Human data are lacking.

Factors that May Disrupt Immune Balance (Increase Th17)​

Many unhealthy habits can disrupt immune balance.
It’s always a good idea to avoid unhealthy behaviors — such as smoking, fast food, overeating, being under a lot of stress, and drinking too much — that can bring your immune system out of balance.
Look to get regular exercise, enough nutrients, sleep, and follow a healthy circadian rhythm.
Below are some unhealthy lifestyle choices and foods that have been linked with Th17 overactivity in limited studies.
Additionally, have in mind that increasing Th17 is not always bad.
The body needs Th17 cells to fight off infections. Th17 activity also sometimes improves blood circulation (NO). That’s why it’s not so easy to target Th17 pathways — experts are still not sure about how beneficial it would be and in which cases [141, 142].
That’s why it’s important to discuss your overall symptoms and health goals with your healthcare provider. The goal is not necessarily to reduce Th1/Th17 but to balance the immune system as a whole.

Lifestyle​

• Chronic psychological stress/anxiety. In a sentence, chronic stress is hypothesized to worsen Th17 overactivity and cause cortisol/glucocorticoid “resistance” [143].
  • Cortisol resistance has been linked with autoimmune/inflammatory issues. Some scientists claim that these issues might, theoretically, worsen before they start to improve when people reduce stress. It’s thought that higher levels of cortisol may be needed to suppress the immune system in this case.
  • Stress causes epinephrine to be released, which is hypothesized to lead to a dominant Th2/Th17 profile. Stress is claimed to affect inflammatory conditions by favoring Th17 immunity, but more data are needed [144].
  • Scientists claim cells from anxious individuals show Th17 dominance (higher amounts of IL-17 and TNF), but clinical data are lacking. In healthy people, glucocorticoids/cortisol decreased excessive Th17 activation, but not in highly stressed people. Anxious people seemed to become insensitive to glucocorticoids [145].
  • Adrenaline, which is a Beta2-AR agonist, may aggravate IL-17-type immune response [146]. Asthma drugs may worsen this response but offer temporary relief. This pathway needs to be studied further.
• Marathons/Excess exercise [147]
• Obesity [148]
• Circadian Rhythm disruption [13]
• EMFs [149]

Diet​

• Gluten [150]
• Iodine excess [151] High levels may result in Th1 elevation [23].
• Arginine [141]
• Frying oils/Smoking (both produce oxysterols) [152]. Also, the enzyme CYP27A1 turns cholesterol into bile and this enzyme can increase oxysterols and therefore Th17 dominance [153].
• High salt diet [154]
• Long-chain fatty acids [155]

Toxins/Infections​

• Free radicals [156]
• Fungal infections [61]
• Viruses
• Intracellular and extracellular bacteria [157]
• Parasites [158]
• Heavy Metals: Cadmium, Mercury and probably Lead and Arsenic[45]
• Flu Viruses [159]
• Klebsiella pneumoniae, Citrobacter rodentium, Candida albicans, Listeria monocytogenes, Salmonella enterica, Mycobacterium tuberculosis [157]
• Chlamydia [160]
• Certain gut microbes [161]

Hormones​

• Leptin [162] – leptin is elevated in obesity.
• Adiponectin [163] Increases Th1 and Th17 cells; known for its insulin-sensitizing effects. Limited studies indicate that it is present in inflamed tissues of patients with rheumatoid arthritis and inflammatory bowel disease.
• Aldosterone [164]. Aldosterone increases blood pressure. Scientists think it might promote Th17 immunity.
• Insulin [113]
• IGF-1 [113]
• Desmosterol, an in-between step to cholesterol production in the body [123]

Supplements​

• Forskolin [139]
• Uric acid (in combination with IL1b and IL18) [165]
• Resveratrol [166] – contradictory
• NAD+/Niagen NAD. (seems to increase Th1 and Th17 cells but may decreases their harmful activity; more research is needed) [3]
• L Casei [167], S Boulardii [168], Bacillus Subtilis [168] (may increase IL-17)

Pathways​

• IL-1(+)… IL-23(+)… TGF-beta*… IL-6(+), IL-21(+)… RORa, RORy(+)… mir-326, mir-301a

Genes and Th17​

STAT3 and mTOR​

Limited studies have associated certain variations in these genes with Th17 immunity.

• RORyt
• IL23
• IL23 Receptor
• IL17

STAT3 is a protein that binds to DNA and increases gene expression.
Scientists believe that STAT3 is essential for the production of the TH17 cells. Theoretically, reducing this protein is supposed to lower Th17 cells [169].
STAT3 is thought to play an important role in autoimmune and inflammatory diseases. See more about STAT3 and a list of potential natural inhibitors.
Increased mTOR may increase Th1 and Th17, hypothetically leading to increased intestinal inflammation [128].
mTOR may increase another protein called hypoxia-induced factor (HIF)-1α, which increases Th17 cells [170].
Some researchers think that inhibiting mTOR may decrease Th1 Cells.

Technical​

mTOR increases glycolysis, which allows Th17 cells to proliferate. This might work through HIF1α. Blocking glycolysis inhibited Th17 development while promoting Treg cell generation. Human data are lacking [129].

Read this post on factors that may inhibit mTOR.

 

[Elie]

What I don't get about the hype surrounding Meformin's "antiaging" scientific evidence is that one of the listed potential side effects is lactic acid build up (acidosis), which, as we know, is indicative of a dominant glycolysis state (diminished energy production) and poor full glucose oxidation through the Kreb's cycle (where most of the energy is produced).

 

[sugarisgreat]

I'm having a hard time understanding this information compared to the negatives about metformin that have been posted on this forum?

 

[Tomaz26]

Problem is that many things portrayed as bad on this forum are actually good when you see data from human and not some mice or rat study. Some of them prooven good and life prolonging:

Omega 3
Metformin
Nuts
Whole grains
Low carb or at least low GI
Exercise, HIT, running, weightlifting
…

 

[Eberhardt]

I

Problem is that many things portrayed as bad on this forum are actually good when you see data from human and not some mice or rat study. Some of them prooven good and life prolonging:

Omega 3
Metformin
Nuts
Whole grains
Low carb or at least low GI
Exercise, HIT, running, weightlifting
…

I am afraid I want do anything but making trouble but ok. What?? with the exclusion of exercise , at least some kinds(and mostly its boring exercise and prolonged that is frawned upon but I'll give you that), what has shown benefits of those things in real life. In Norway there was a huge study - largest ever - of supplementation with omega3 spanning about 25 years which showed only increased all-cause mortality. And those others?? do feel welcome to show some examples

 

[Tomaz26]

Nuts For Longevity: Daily Handful Is Linked To Longer Life :
View: https://www.npr.org/sections/thesalt/2013/11/21/246549388/nuts-for-longevity-daily-handful-is-linked-to-longer-life
​

The Whole Truth: Whole Grains Increase Longevity, Studies Say:​

Whole Grains Increase Longevity - Blue Zones

Whole grains have been highlighted in the media quite often recently and are a staple in the Blue Zones.

www.bluezones.com

Eating Some Carbs, But Not Too Many, Could Help You Live Longer, Study Suggests: Eating Some Carbs, But Not Too Many, Could Help You Live Longer, Study Suggests​

Like I said does not need to be low carb but at least low GI so not too much sugars and simple carbs..

 

[Tomaz26]

Same with heart rate. Low is good not high as I know many people try to increase hr here and frown upon having low resting hr

What your resting heart rate reveals about your longevity: What your resting heart rate reveals about your longevity | Considerable​

 

[Eberhardt]

Nuts For Longevity: Daily Handful Is Linked To Longer Life : ​

View: https://www.npr.org/sections/thesalt/2013/11/21/246549388/nuts-for-longevity-daily-handful-is-linked-to-longer-life​

​

The Whole Truth: Whole Grains Increase Longevity, Studies Say:​

Whole Grains Increase Longevity - Blue Zones

Whole grains have been highlighted in the media quite often recently and are a staple in the Blue Zones.

www.bluezones.com

Eating Some Carbs, But Not Too Many, Could Help You Live Longer, Study Suggests: Eating Some Carbs, But Not Too Many, Could Help You Live Longer, Study Suggests​

Like I said does not need to be low carb but at least low GI so not too much sugars and simple carbs..

Well, appreciate the effort. though this is not very significant at all. To take the nuts first. It only shows that people who eats nuts are living longer, not that they live longer because they eat nuts. Since other studies show that (not that Im horribly against nuts ) if you live the same lifestyle and just eat or dont eat nuts the effect disappears. They are also probably more likely to were baggy clothes or see more artsy movies, none of which directly adds to their lifespan.

The grain thing is just sloppy - gives no evidence at all just a statment and conclusion completly unrelated to any mechanism. It only proves that whole grains are touted as being good. (anthony colpos book whole grains empty promises is a good book),

the carb thing is beyond description. They didnt even bother about what else then the carbs people where eating.


It needs evidence not clickbait. and Im more then willing to look at it if you have any

 

[Eberhardt]

Same with heart rate. Low is good not high as I know many people try to increase hr here and frown upon having low resting hr

What your resting heart rate reveals about your longevity: What your resting heart rate reveals about your longevity | Considerable​

High in itself is not claimed to be good. Its just that a healthy metabolism gives a higher heartbeat, which can be seen on studies of healthy hunter gatherers f.ex. The opposite is not true - that high heartrate means healthy. Most people having a higher resting heartbeat have it due to adrenalin and other related conditions

 

[Tomaz26]

Evaluation of Dietary Patterns and All-Cause MortalityA Systematic Review:​

Evaluation of Dietary Patterns and All-Cause Mortality

This systematic review describes the combinations of foods, beverages, and food groups that were associated with beneficial outcomes, according to existing research on diet and nutrition.

jamanetwork.com

Findings In this systematic review of 1 randomized clinical trial and 152 observational studies on dietary patterns and all-cause mortality, evidence demonstrated that dietary patterns characterized by increased consumption of vegetables, fruits, legumes, nuts, whole grains, unsaturated vegetable oils, fish, and lean meat or poultry (when meat was included) among adults and older adults were associated with decreased risk of all-cause mortality. These healthy patterns consisted of relatively low intake of red and processed meat, high-fat dairy, and refined carbohydrates or sweets.

So PUFA, nuts, legumes, whole grain, fish are good? There are thousand of studies proving that.

I know I risk being banned now, but I was asked to post evidence, so i did. Working from mobile, can post hundreds more for exercise etc..

 

[Tomaz26]

Well, appreciate the effort. though this is not very significant at all. To take the nuts first. It only shows that people who eats nuts are living longer, not that they live longer because they eat nuts. Since other studies show that (not that Im horribly against nuts ) if you live the same lifestyle and just eat or dont eat nuts the effect disappears. They are also probably more likely to were baggy clothes or see more artsy movies, none of which directly adds to their lifespan.

The grain thing is just sloppy - gives no evidence at all just a statment and conclusion completly unrelated to any mechanism. It only proves that whole grains are touted as being good. (anthony colpos book whole grains empty promises is a good book),

the carb thing is beyond description. They didnt even bother about what else then the carbs people where eating.


It needs evidence not clickbait. and Im more then willing to look at it if you have any

Ok so you post contra please. That refined carbs are good, high sugar intake is good etc. Doubt you will find any..
Just stop, there are literally thousands of studies showing what a good diet is and never have I saw high sugar, meat, saturated fat come on top, except here of course. Same for exercise. If one was to apply knowledge from here it would be lay on the couch all day and eat only ice cream and boatloads of refined sugar. Funny how not a single study showes any benefit of that on the contrary such lifestyle lowers life span..
But yeah, sure is nice to get an excuse to be lazy, fat and eat ice cream all day. We all seek easy way out and for evidence that would support that view

 

[Eberhardt]

Evaluation of Dietary Patterns and All-Cause MortalityA Systematic Review:​

Evaluation of Dietary Patterns and All-Cause Mortality

This systematic review describes the combinations of foods, beverages, and food groups that were associated with beneficial outcomes, according to existing research on diet and nutrition.

jamanetwork.com

Findings In this systematic review of 1 randomized clinical trial and 152 observational studies on dietary patterns and all-cause mortality, evidence demonstrated that dietary patterns characterized by increased consumption of vegetables, fruits, legumes, nuts, whole grains, unsaturated vegetable oils, fish, and lean meat or poultry (when meat was included) among adults and older adults were associated with decreased risk of all-cause mortality. These healthy patterns consisted of relatively low intake of red and processed meat, high-fat dairy, and refined carbohydrates or sweets.

So PUFA, nuts, legumes, whole grain, fish are good? There are thousand of studies proving that.

I know I risk being banned now, but I was asked to post evidence, so i did. Working from mobile, can post hundreds more for exercise etc..

I am at least not going to complain about you posting BUT i do disagree that its anything resembling proof. by all means its not proof of the opposite either. The thing is it might just as well be the effect of eating whole foods. Also its a meta-studie which is initself highly suspicious as it means they can pick which studies to use. Point is it doesnt show what the 185 groups they analyzed ate and what the alternative was. Or if they just trained more - there is a lot of different lifestyle choices contributing to health/unhealth. And this only shows correlation... if its true at all as its a meta study. SO since there are more precise studies that show particular effects there is no reason to draw any conclusions from something heaping so many factors together, possibly sherry-picks and also doesnt show the alternatives. Probably what you describe is at least better then stressing, sedentarianism, mcdonalds, booze and sleep deprivation. No idea how that could prove its better then the general theme here - even if I like most here probably (hopefully), have points I disagree on.

 

[Eberhardt]

Ok so you post contra please. That refined carbs are good, high sugar intake is good etc. Doubt you will find any..
Just stop, there are literally thousands of studies showing what a good diet is and never have I saw high sugar, meat, saturated fat come on top, except here of course. Same for exercise. If one was to apply knowledge from here it would be lay on the couch all day and eat only ice cream and boatloads of refined sugar. Funny how not a single study showes any benefit of that on the contrary such lifestyle lowers life span..
But yeah, sure is nice to get an excuse to be lazy, fat and eat ice cream all day. We all seek easy way out and for evidence that would support that view

I am not inclined to reproduce everything that has been posted for a decade here including thousands of studies around the forum ; also check out Peat articles on his webiste. I cant say you are trolling and its ok to disagree but since you claim they dont even exists and only post sloppy articles its hard to take it seriously. I hope you will check it out as it gives what you are metioning. tons of reserach confirming this. I do also want just for fun to add that Peat recomends being active, creative social and inquisitive - so while being no fanboy that would be a very unpeat thing to do. (maybe except the icecream)

 

[Tomaz26]

I do agree with many RP articles and know that he is faar smarter than I am and so are many of posters here on RP forum, but I just cannot overlook when study after study show how sugar and high GI is bad, ditto for refined carbs and on the other hand fish and olive oil and whole grains, nuts come on top each and every time from AHA, cancer assosiation etc.
10.000 steps a day, mediterranean diet it is! ?

 

[Eberhardt]

I do agree with many RP articles and know that he is faar smarter than I am and so are many of posters here on RP forum, but I just cannot overlook when study after study show how sugar and high GI is bad, ditto for refined carbs and on the other hand fish and olive oil and whole grains, nuts come on top each and every time from AHA, cancer assosiation etc.
10.000 steps a day, mediterranean diet it is! ?

I understand you. I just dont find them convincing as they are to unprecise and find the more direct evidence more convincing..

A pro pos the carb thing. It is also relevant how well the glucose metabolism is working. If its not in good shape u canbget problems. Also it if I understand it correctly is relevant what kind of sugars and what they are co-ingested with. A lot of people eats sugars with fat which competes for handling and thus blocks the potential proper use of glucose. I think the main jist is that glucose-metabolism is highly preferable to fat aoxidation for fuel and that increasing carbs and decreasing fat tends to help this. I am personally not a high sugar eater any more as I do better on white rice and white potatoes :)

 

[Tomaz26]

Agree. Most of my intake is carbs, I just think I went too much into ice cream, sweets and refined carbs and fruits since RP. So now I try to again balance things a bit more by adding oats and other whole grains, dialing down on sweets and high GI fruits, adding some nuts back to my diet. Less red meat and more fish. But its still mostly carbs with full fat milk and coconut and mct oil, some olive oil too. Just more variety and more movement again.

 

[Eberhardt]

Agree. Most of my intake is carbs, I just think I went too much into ice cream, sweets and refined carbs and fruits since RP. So now I try to again balance things a bit more by adding oats and other whole grains, dialing down on sweets and high GI fruits, adding some nuts back to my diet. Less red meat and more fish. But its still mostly carbs with full fat milk and coconut and mct oil, some olive oil too. Just more variety and more movement again.

Sounds quite ok to me! :) and also I dont think a little pufa from food is that bad, even if I dont eat much of it - I think the refined oils and suplements are more to worry about. I do sometimes eat sugar but only suplemental if I notice I am "wired" and tired. I never had much success with icecream myself. Maybe when I was higly underwight ten years ago or so but nah. I try olive oil from time to time but I always get sensitive mucus membranes. I think enough protein and salt and not to mych liquid also is an importamt aspect

 

[mostlylurking]

What I don't get about the hype surrounding Meformin's "antiaging" scientific evidence is that one of the listed potential side effects is lactic acid build up (acidosis), which, as we know, is indicative of a dominant glycolysis state (diminished energy production) and poor full glucose oxidation through the Kreb's cycle (where most of the energy is produced).

Metformin blocks thiamine function which disrupts the Kreb's cycle resulting in lactic acidosis which equals Warburg's cancer metabolism.

Metformin Is a Substrate and Inhibitor of the Human Thiamine Transporter, THTR-2 (SLC19A3) - PubMed

The biguanide metformin is widely used as first-line therapy for the treatment of type 2 diabetes. Predominately a cation at physiological pH's, metformin is transported by membrane transporters, which play major roles in its absorption and disposition. Recently, our laboratory demonstrated that...

pubmed.ncbi.nlm.nih.gov

Hiding in Plain Sight: Modern Thiamine Deficiency

Thiamine or vitamin B1 is an essential, water-soluble vitamin required for mitochondrial energetics—the production of adenosine triphosphate (ATP). It is a critical and rate-limiting cofactor to multiple enzymes involved in this process, including ...

www.ncbi.nlm.nih.gov

 

[tankasnowgod]

I do agree with many RP articles and know that he is faar smarter than I am and so are many of posters here on RP forum, but I just cannot overlook when study after study show how sugar and high GI is bad, ditto for refined carbs and on the other hand fish and olive oil and whole grains, nuts come on top each and every time from AHA, cancer assosiation etc.

Oh, sure you can. You've proven you are quite adept at overlooking studies just by your posts in this thread!

First, you overlooked the fact that the study posted in the OP was an in vitro study. Sure, they used human cells, but still, an in vitro study is always going to be less applicable to real living human beings than an in vivo study, even if such a study were done in rats or mice.

Second, you overlooked the studies talked about in NPR, bluezones.com and livescience links you posted, and instead appeared to rely on third party opinions about those studies from those organizations themselves. Why didn't you seek out the studies they mentioned, and post those links instead? You have access to tools like Pubmed and Google Scholar, just like the rest of us on this forum do.

Is it really third party opinions of studies that you can't overlook? Even when they come from organizations with an obvious bias like The American Heart Association? The AHA makes money in part by charging companies so that they can use the "heart check" logo on their product. At one time, even Cocoa Puffs had a heart check logo-

Is Cocoa Puffs no longer heart healthy?

Until recently, Cocoa Puffs enjoyed the endorsement of the American Heart Association (AHA) as a heart-healthy food. <br /><br />For a price, the AHA will allow food manufacturers to affix a heart "check mark" signifying endorsement by the AHA as conforming to some basic "heart healthy"...

www.cureality.com

And the only true "study" you posted was a meta-analysis from Jama, and seeing as you just copied one of the first paragraphs, labeled "findings," I think it's highly likely you didn't read or understand this study, either. Or the fact that meta-analyses can be easily manipulated, simply by picking studies that seem to support your hypothesis.

If you want to post studies that are contrary to Peat's ideas, that's great, but I think you should have at least bothered to look at the "Materials and Methods" section of such a study, and reviewed the results. It's also helpful to write a few things about the study from your own understanding, and maybe some questions it raised. Just bulk posting studies you haven't read isn't helpful, and certainly doesn't prove anything.