Interesting… had not known Urolithin A was anti-inflammatory:
Urolithin A (Uro-A) is an anti-inflammatory and cancer chemopreventive metabolite produced by the gut microbiota from the polyphenol ellagic acid. However, in vivo conjugation of Uro-A to Uro-A glucuronide (Uro-A glur) dramatically hampers its activity.
FWIW attached is a copy of the paper.
proceedings-79-00012.pdf (846.7 KB)
Another interesting editorial on inflammation and cardiac - with a focus on Moringa, which I regularly add to my smoothies.
Louisa et al. from the University of Indonesia have performed a systematic review on the role of Moringa oleifera Lam [Moringaceae] in cardiovascular or metabolic disorders, in addition to its high nutritional value. Moringa oleifera Lam. is a native plant of several Asian countries and is reported to provide potential benefits against oxidative stress and inflammation, modulating glucose and lipid metabolism and preventing end-organ damage. They have also covered the importance of altering the gut microbiota in metabolic syndrome in addition to the supporting data for the role of Moringa oleifera Lam. on various signaling pathways activated during inflammation and oxidative stress. Liu et al. have studied the molecular basis of the effect of ShenLian extract on atherosclerotic plaques in vitro and in vivo .
Up until at least 1.6 g/kg and perhaps even as high as 2.2 g/kg it’s beneficial to increase protein intake for muscles synthesis
This is just 1 article but you can find dozens more
100%, if I ate more BCAA, I’d have bigger muscles. But that’s not my goal. It would also take me out of my ketogenic diet protocol, result in higher mTOR stimulation, possibly higher cancer risk (you know all the associational studies). I assess the cumulative risk skewed to reduced longevity. The default plan is to continue to maintain muscle mass and strength as I age through exercise, not needing additional protein.
I just find the idea of building muscle without much protein fascinating, and yet another wonder of human evolutionary physiology.
More inflammation research:
The causes of neuroinflammation can be roughly divided into the following domains: viral infection, autoimmune disease, inflammation from peripheral organs, mental stress, metabolic disorders, and lifestyle. In particular, the effects of neuroinflammation caused by inflammation of peripheral organs have yet unclear mechanisms. Many diseases, such as gastrointestinal inflammation, chronic obstructive pulmonary disease, rheumatoid arthritis, dermatitis, chronic fatigue syndrome, or myalgic encephalomyelitis (CFS/ME), trigger neuroinflammation through several pathways. The mechanisms of action for peripheral inflammation-induced neuroinflammation include disruption of the blood-brain barrier, activation of glial cells associated with systemic immune activation, and effects on autonomic nerves via the organ-brain axis.
Source referenced:
Here we discuss the role of inflammation in stress-induced diseases and suggest a common pathway for stress-related diseases that is based on chronic mild inflammation. This framework highlights the fundamental impact of inflammation mechanisms and provides a new perspective on the prevention and treatment of stress-related diseases.
Conclusion: Glucosamine and chondroitin supplementation may lower systemic inflammation and alter other pathways in healthy, overweight individuals. This study adds evidence for potential mechanisms supporting epidemiologic findings that glucosamine and chondroitin are associated with reduced risk of lung and colorectal cancer.
@tongMD Re inflammation, I normally only check hsCRP regularly. It’s pretty much zero. Any benefit/insight to add IL-6 or TNα to the panel, both available to me?
Not really unless you’re looking at something specific
No, just general wider inflammation scan. If I had all 3 data points and compared them to the inflammation literature (where they readily include IL-6/TNα), what quartile of systemic inflammation would I fall in? Just a fishing expedition.
It seems we (males) would want to track IL-6 and TNF-a over time. Not sure how hard / expensive these are to test for…
Results
People with higher multi-morbidity percentiles had significantly higher IL-6 and TNF-α levels compared with those with lower multi-morbidity percentiles. Tests for trend across five multi-morbidity quintiles were significant among women for IL-6 and among participants 70 years of age or older for IL-6 and TNF-α. IL-10 was not associated with multi-morbidity percentiles.
Not expensive, I was thinking of adding to my next panel. That’s what I was thinking, I could compare myself to the literature.
Ah, made a mistake in my last quote - in that study it says they only significant for females, but still I’d like to know how my levels are trending…
Conclusions
Multi-morbidity percentiles may be a useful clinical index of biological age for future studies, particularly in women and people 70 years of age and older.
“It seems we (males) would want to track IL-6 and TNF-a over time. Not sure how hard / expensive these are to test for”
Why only males and not females? I tried to get both my IL-6 and TNF-a blood levels tested where I live. My blood was sent to two different labs in the country and they were still unable to test TNF-a, which surprised me since TNF-a is so commonly described in studies as an important inflammatory marker. With regard to IL-6 I was told by the laboratory it can fluctuate quite a bit over the course of the day, but admittedly I didn’t look into the validity of this comment further. It was such a hassle that I never tried to test these markers again. But this was in Europe; perhaps American members may have a different experience.
More interesting research on inflammation and aging, and drugs that treat it:
Increased inflammatory activity accompanies normal brain aging. Aging retardation can be achieved in mice by inhibiting activation of hypothalamic nuclear factor‐kB (NF‐kB) inflammatory pathways (Zhang et al ., 2013).
Three drugs extend lifespan of UM‐HET3 mice in a sex‐specific way: acarbose (ACA), 17‐α‐estradiol (17αE2), and nordihydroguaiaretic acid (NDGA), with more dramatic longevity increases in males in each case. In this study, we examined the effect of these anti‐aging drugs on neuro‐inflammation in hypothalamus and hippocampus.
We found that age‐associated hypothalamic inflammation is reduced in males but not in females at 12 months of age by ACA and 17αE2 and at 22 months of age in NDGA‐treated mice. The three drugs blocked indices of hypothalamic reactive gliosis associated with aging, such as Iba‐1‐positive microglia and GFAP‐positive astrocytes, as well as age‐associated overproduction of TNF‐α. This effect was not observed in drug‐treated female mice or in the hippocampus of the drug‐treated animals.
On the other hand, caloric restriction (CR; an intervention that extends the lifespan in both sexes) significantly reduced hypothalamic microglia and TNF‐α in both sexes at 12 months of age. Together, these results suggest that the extent of drug‐induced changes in hypothalamic inflammatory processes is sexually dimorphic in a pattern that parallels the effects of these agents on mouse longevity and that mimics the changes seen, in both sexes, of long‐lived nutrient restricted or mutant mice.
The above study is showing significance only in females - so its more likely to be useful in females it seems, but I’m a male and I suspect these markers / measures are also important for males.
How did they get over the likely low blood-brain barrier penetration of NDGA?
Last I heard of NDGA, I recall FDA pulling it from GRAS because of cystic nephropathy in rats. I would presume even NDGA derivatives will need some time before I’d consider them.
I don’t think “BCAAs are bad and cancer” paradigm makes a whole lot of sense to me but happy to be proven wrong. Seems like getting a balance of mTOR on and off to preserve functional strength, and avoiding “mTOR hyperactivation” is the key - especially healthspan.
I see plenty of people with tons of muscle (non steroid/hGH users) use milk or whey protein supplements with a lower than average risk of cancers. High-intensity exercise is literally highly inflammatory btw, yet if I told you some drug causes your inflammatory markers to go up in a dose-dependent response - one may have a knee-jerk reaction to probably avoid the highest levels at the very least. Yet we have excellent evidence that it is one of the best proven anti-aging “drugs” out there with a very strong dose dependent response (short of some athletes that overtrain)