I do not think NMN will work.
2018/07/30 20:20
I do not think NMN will let anyone young forever. No molecule can target all cells.
Basic enzymology
2018/07/26 09:35
NAD+/NADH are crucial redox pair and the key substrate for the electron-transfer chain and ATP biosynthesis, is also a protein substrate, mainly NADH dehydrogenase, the first enzyme complex in the mitochondrial electron-transfer chain. If you have a little basic enzymology concept, the substrate molecule has to bind to the active site of the catalytic center to proceed the catalysis. The binding affinity of the enzyme is usually at micromolar level, uM, which is 3 orders smaller than the milimolar cellular concentration of NADH. It is not easy to have cells to exhaust the NADH concentration to as low as its binding equilibrium constant, ~ uM, to influence its catalytic activity. A decrease from 1 mM down to 100 uM (a 10X decrease), is still ~ 100 times higher than its binding affinity (we usually use Kd. or dissociation equilibrium constant to express affinity. Km is another parameter if you care to dig in more about enzyme kinetics), so all the enzyme molecules will still be saturated by available NADH in the cells. Thus, a 40% decline in cellular NADH/NAD+ in senior people Sinclair found is trivial and has insignificant effect on the normal function of the key enzyme NADH dehydrogenase to initiate the electron flow down the chain to generate the coupled ATP formation.
How much NMN one have to take to make an impact ?
2018/07/26 09:24
I have seen enough similar claims for the specific effects of one compound without convincing experimental and theoretical support. Medical publication is so frivolous and more than half of the papers need to have careful rethinking about the conclusions drawn from the data. The NMN saga is no exception to me. I have not done a quick estimation about how much NMN you have to take to boost up your cellular concentration by an order of magnitude, or just double. Even this is not a simple issue, pharmacokinetics is always a very complicated agglomeration of many compartmentation, transfer, etc. steps. I believe tracer experiment to follow the turnover rate of NAD+/NADH is available and must be very complex function. Another side reaction we need to pay attention is the leakage of the electron-transfer chain getting bigger when you are aging simply due to the function of those enzymes decline, thus you supply more NADH substrate, you will also generate more free radicals, which only do more unwanted damage.
摸 象 或 (不?) 著 木目(mbr8879576) 於 2018-07-26 10:04 回覆:
感謝賜教! Your 開示 is very convincing. Thanks a lot for taking so much time and effort to educate me about this subject. I did see someone (Taking NMN) questioning how much of NMN dosage is needed to make an impact to 返老還童。 Obviously﹐mice has an advantage of being light weighted when compared with human.
摸 象 或 (不?) 著 木目(mbr8879576) 於 2018-07-27 01:28 回覆:
1% instead of 2% → To reach same level with the lab mice, it will cost around > $2,000 USD per month.
摸 象 或 (不?) 著 木目(mbr8879576) 於 2018-07-27 02:21 回覆:
每月 兩千美金 對 少數人 或不是問題 ?! 对 蘋果手機 的發明人 而言﹐每分鐘 兩千美金 或也不是問題 ?! 何況 將來 價錢 必然會 大降 ? !
摸 象 或 (不?) 著 木目(mbr8879576) 於 2018-07-30 07:13 回覆:
『The dosages in most resveratrol supplements are typically much lower than the amounts that have been shown beneficial in research. Most supplements contain 250 to 500 milligrams. To get the dose used in some studies, people would have to consume 2 grams of resveratrol (2,000 milligrams) or more a day.』 ~ https://www.webmd.com/heart-disease/resveratrol-supplements#2
Story of promoting the sales of L-arginine
2018/07/26 09:07
Yes, the label of professor and Harvard Medical School are glaring. This story reminds me of my collaborator, Fred Murad, a noble laureate. The prize awarded his seminal finding on cGMP involved in nitric oxide function is an accomplishment hard to ignore. However, his later main efforts on organizing meetings and promoting the sales of L-arginine (the substrate of nitric oxide synthase)+ antioxidant supplements and even put his Nobel medallion on the surface of the container seems to go off the limit of a true scientist. L-arginine, is similar to NAD+, such an abundant compound, ~ mM concentration in the cells and easily replenished by various protein food sources. Such high concentration molecules seldom face the destiny of insufficiency, even during your aging period. Similar story for L-arginine as the source for NO. It is very rare to see report that there is case that L-arginine insufficiency could be a nutritional or clinical issue. Anyone raised such comment will face extra securitization.
Possibly a hoax
2018/07/25 10:30
My Ph.D. thesis is on the subject of mitochondrial enzyme complex, so I have some knowledge about mitochondria in energy metabolism. Q10 plays important role in the mitochondrial energy production process, but your body will synthesize enough amount of it. Don't waste your money and time on these many ads trying to promote the selling of various supplements. You always get confused. Keep balaced nutrition, exercise daily, do not put yourself under stress. Use the Qigong and meditation to help you to achieve a peaceful mind. These perhaps weigh much over those supplements. I never heard about deficiency of NAD+ or NMN+ as long as your protein intake is normal, as both the nicotinamide part and the adenine part of NAD+ are from amino acids. Overall, a balanced nutrition is all that you need. Any supplement if ingested in access, only add unwanted burden to your liver and kidney. Didn't I send you the hoax of CoQ (Q10) before in one of my comments? This fat-soluble antioxidant is on the shelf for anyone to buy, but it is actually a handy source of free radical once you intake. Unless you take statins for a long time, then replenish Q10 may justify, as the precursor of both cholesterol and Q10 are the same. Best Regards, 蔡亞麟 Ah-lim Tsai, Ph.D. Division of Hematology, Internal Medicine & Biochemistry and Molecular Biology Program University of Texas Medical School at Houston Rm. 5.290, 6431 Fannin, Houston, TX 77030 Tel: (713)500-6771 FAX: (713)500-6810 e-mail: Ah-Lim.Tsai@uth.tmc.edu https://med.uth.edu/internalmedicine/faculty/ah-lim-tsai-phd/
Dr. Jason Fung - 間歇性斷食 intermittent fasting
2018/07/25 09:27
VIDEO VIDEO
懇請不吝賜教?
摸 象 或 (不?) 著 木目(mbr8879576) 於 2018-08-14 06:11 回覆:
Dr. Sarah Hallberg is correct。 VIDEO
摸 象 或 (不?) 著 木目(mbr8879576) 於 2018-07-25 09:31 回覆:
What is intermittent fasting?VIDEO
摸 象 或 (不?) 著 木目(mbr8879576) 於 2018-07-25 10:04 回覆:
How to reverse diabetes type 2VIDEO
摸 象 或 (不?) 著 木目(mbr8879576) 於 2018-07-27 08:07 回覆:
Why fasting bolsters brain power ? ! VIDEO
摸 象 或 (不?) 著 木目(mbr8879576) 於 2018-08-14 06:23 回覆:
3 Ways To Do Intermittent Fasting: Easy, Medium & Extreme - Dr. Becky Gillaspy VIDEO
摸 象 或 (不?) 著 木目(mbr8879576) 於 2021-09-15 14:18 回覆:
飢餓醫師 劉乂鳴 VIDEO
。
2018/07/25 00:17
血壓常上飆,我吃的是Micardis HCT 40mg
李兄有無更好的治本方法?
摸 象 或 (不?) 著 木目(mbr8879576) 於 2018-07-27 08:31 回覆:
Please try 3 Ways To Do Intermittent Fasting ↓ VIDEO
哦 ? ! Statin ~ Cholesterol Drug
2018/07/13 19:35
Statin Scam Exposed: Cholesterol Drugs Cause Rapid Aging, Brain Damage And Diabetes VIDEO https://www.youtube.com/results?search_query=Statin+cholesterol+myth
懇請不吝賜教?
摸 象 或 (不?) 著 木目(mbr8879576) 於 2018-07-22 22:45 回覆:
有些 華洋西醫﹐ 考過 執照 之後 就不再 接觸 醫學 新知 ← 唯一 新知 來自 各大藥廠﹐ 上門推銷新药 (如 Pfizer 推銷 Lipitor ) Sales Ladies。 換言之﹐妳 不如自行上網﹐You-Tube or Google 或能獲得 更可靠 医药新知 ?!