"Lest we off ourselves . . ." : build on this thread

#2

This is not the example you are looking for because it’s what I did NOT do, but I never give up an opportunity to rant about but my biggest regret in life :slight_smile:

It was just as damaging than actively taking something risky.

My biggest regret in life is having multiple bad cardiologists:

  1. who didn’t tell me about ezetimibe

  2. who didn’t know that my ‘great ratio’ was not gong to protect me

  3. who didn’t tell me that I needed to take statins, even if I didn’t feel well, because I was causing irreversible damage … and to just take them until they one day invent an alternative… hello repatha

  4. and that I had an idiot cardiologist who kept putting off giving me an rx for repatha because he was trying to get it for me for free, even after I said, yeah, but what about I pay in the meantime!

Of course I would have a different kind of regret had been a person who was never proactive and never went to cardiologists, but I think that would feel better than having made the effort and receiving bad advice. I’ll never know!

3 Likes
#3

I think the worst thing is drinking alcohol. I almost never drink, but during college, under the influence of the dormitory party environment, I had to drink twice. The key point is that I got drunk both times. Even just 1 liter of beer makes me drunk. Although I took compounds like curcumin for protection before and after drinking, it may have already caused permanent damage to my brain.

This study shows that heavy drinking during adolescence disrupts the normal function of brain cells and impairs communication between them, leading to permanent dysregulation of brain cells. Even after stopping alcohol consumption, these changes may be irreversible.

The scariest thing is that now I actually miss the feeling of being drunk—my body and mind felt extremely relaxed, as if I were in heaven—and this has left a permanent memory in my brain. I think I will have to overcome the temptation of alcohol for the rest of my life.

I fucked up.I thought that with the help of anti-aging compounds, I could avoid the side effects of alcohol. At the time, I was taking far more types of compounds than Bryan Johnson, which made me extremely arrogant. Even though I knew the harm alcohol causes to the human body, the influence of the party atmosphere plus my arrogance defeated me. I am far weaker than I ever imagined.

2 Likes
#4

If you didn’t get drunk a few times when you were young, you haven’t lived, not that I recommend it. :slightly_smiling_face:

4 Likes
#5

My wife has worked through these issues including, most disappointingly, dealing with multiple OB/GYNs who are functionally stone age incompetent with respect to HRT. Together she and I traced the research history back through the now infamous research paper that, with intention on the part of the PI, falsely reinforced beliefs about the harms of HRT. I won’t go through the years of challenges my wife endured educating physicians and getting them to read and correctly interpret the actual research – but she is now on a comfortable course of HRT, including the patch, progesterone capsules, compounded testosterone cream, and vaginal estradiol, which is a contemporary protocol for informed practitioners. The only residual issues she has were caused by one nine month span in which her practitioner at the time would prescribe only a trivially low level of estrogen. Thankfully, her current practitioner is up to date on the research and the number of those like her seem to be growing.

I infer you have concluded that it is no longer advisable to return to full HRT. I know that that clinical evidence on that issue is evolving toward longer acceptable intervals.

4 Likes
#6

Rob Tuck, thanks for your post. Like your wife I have had my share of experience with docs who were not current. (My PCP thanked me a few times for things I told him but he is still way behind on a lot of issues.) I have an upcoming appointment with the breast cancer “survivor clinic”; in answer to my prodding they said they do “sometimes” prescribe vaginal estrogen for survivors. I will also talk to them about systemic estradiol.

And like Beth, I have had frustrating meetings with my cardiologist, a lipidologist, no less. He wasn’t even aware of Lp(a) when I first brought it up two years ago. But, I will say, he was willing to listen-- especially after I dragged out my genetic report and told him that Repatha was the one thing we currently have that will lower Lp(a) by around 20%. So, he agreed to prescribe it and I am grateful for that.

2 Likes
#7

Thank you for your comfort, but I think those who smoke weed or do meth probably have the same mindset, haha. Those who never care about their own health might think it’s no big deal, but in the biohacking community, this is indeed an experience that deducts major points. I knew very early on that alcohol is a Group 1 carcinogen, so I never paid attention to negative research on alcohol because I believed I would never drink. But in reality, under the influence of the party atmosphere, I took a gamble. Without any proper investigation, I jumped to the conclusion that having a drink or two once in a while wouldn’t matter, just to convince myself. Not only that, but I also got drunk. Recalling the whole event still terrifies me. My arrogance completely consumed me. Maybe those drunken domestic abusers had the same mindset the first time they drank. Oh god.

Even a very small amount of alcohol can significantly increase dopamine levels in the nucleus accumbens, the brain’s core reward area, making people feel happy. But this kind of easy-access dopamine, in the long run, produces negative consequences. We should pursue dopamine that produces positive effects in the long term. Here’s a simple example: @RapAdmin , after successfully making rapamycin toothpaste, must feel happy. He knows this kind of happiness is far more sophisticated than cheap alcohol. It drives @RapAdmin to continue hands-on practice, optimizing his health and receiving long-term positive feedback. Alcohol does exactly the opposite. Looking back now, perhaps it wasn’t my weak willpower, but the environment that defeated me. I chose Diet Coke nine times out of ten parties, but just that one time, my wishful thinking won. Maybe it’s not my fault. Even as I write this experience, I feel happy because I know many teenagers will see this and give up alcohol.

1 Like
#8

How many college guys even give a second thought as to try to protect themselves with a supplement?!

1 Like
#9

But you know that anxiety, particularly health anxiety, is also highly detrimental to your health, right?

Drinking on college really isn’t a big deal IMO, and I don’t think there’s any evidence that you do any long-term harm. You shouldn’t try to hold yourself to “perfect” standards.

7 Likes
#10

I’m with @relaxedmeatball meatball on this one. In many cultures, and at specific times in your life, a little alcohol goes a long way towards helping in social bonds. And social bonds are probably one of the most important factors in a long (and good) life.

I’ve largely stopped drinking alcohol (like, it seems, much of the Bay Area / tech scene) but occasionally with friends I’ll have a drink. You don’t have to drink alcohol though, there are lots of good “mocktails” now. But I also wouldn’t worry about the occasional glass, or even (when you’re younger) getting drunk occasionally.

Things are rarely black and white. If a little alcohol helps you relax and enjoy your social time more, it might even extend your life.

7 Likes
#11

I agree with RapAdmin. I think the horror stories from influencers about “any alcohol is dangerous” is way overstated. Yes binge drinking is terrible. But in eight years in Italy I never met anyone who didn’t drink wine at meals. Italuans have significantly longer life spans than Americans. its not that wine extends life, but it clearly doesn’t reduce it. Italians also eat a Mediterranean diet with lots of fish and olive oil, walk a lot and have amazing social connections. But wine usn’t killing them

3 Likes
#12

I’m not surprised to receive criticism. After all, I’ve seen plenty of uncomfortable comments under many science videos. I don’t consider myself an exception, especially since the amount of information conveyed through text is quite limited. I think the most important thing is to respond to valuable comments. I believe that the study widely discussed in many private anti-aging clinic communities — no one actually clicked into it, let alone understood it. As for whether alcohol is harmful, there’s no point in further discussion. Also, this isn’t so-called anxiety; it’s regret. Just like a student admitted to MIT doesn’t feel anxious about making a mistake on an arithmetic problem in middle school. Anyway, I won’t bother explaining the difference between anxiety and regret anymore — it’s a pure waste of time. In addition, let me share another paper. The two papers are better read together.

https://www.pnas.org/doi/abs/10.1073/pnas.2122477119

1 Like
#13

Buy Naltrexone tablets and if you find yourself drinking even though you don’t want to, you could pop one simultaneously and reduce the positive association.

3 Likes
#14

And it will kill your appetite because it negatively affects the taste of most everything. Kill two birds with one stone: stop drinking and lose weight.

1 Like
#15

Often referred to in literature is a thing called a “right of passage”. These are the things that we experience as we grow from youth to older age. IMO, they are an important part of life. Don’t want to miss too many experiences.

The biggest warning:
“Large U.S. epidemiological studies suggest about 1 in 5 to 1 in 8 people who start drinking eventually develop alcohol dependence.”
That is a scary number. Some people literally process alcohol differently in their bodies.
Also, certain personality patterns increase the risk of substance addiction.

Fortunately, I don’t have an addictive personality for anything. Quite the opposite; too much of a “been there, done that” sort of thing. I haven’t drunk alcohol since my youth, not for health reasons but just because I grew out of the taste for beer and liquor.
I also smoked for a while when I was in the Navy, because that is what everyone did. If you didn’t smoke or drink, you were the odd man out.

On the whole, I have few regrets, and then mostly for what I didn’t do.

4 Likes
#16

Not criticism IMO. Just knowledgeable caring people sharing their thoughts. I have seen all sides of alcohol and can respect differing opinions on it. A difficult lesson to learn, for me at least, was that there is no free lunch: all choices toward attractive value preclude other choices toward attractive value. While I drink very rarely these days, I would not for moment consider trading my cherished memories with friends and loved ones if I were given the opportunity to erase those times of consumption. One other thought about free lunch: risk-mitigation is similarly complex. Consider for example: other things being equal, will you be less healthy after drinking one beer a day for 10 years, or after consuming a slice of apple pie a day for 10 years, or after living in a large city for 10 years? The answer to that question might be more complex and possessed of more knock-on strands of causality than first appearances suggest.

1 Like
#17

Nah, there is no question in my mind that a beer a day is better.

#18

Sounds like you should be selling the opposite experience to anxiety and regret.
Cole’s anti-aging alcohol called “Heaven” consists of:
An 80-proof vodka infused with herbal extracts, vitamins, minerals, and amino acids.
Party wisely my friends :dancing_women: :clinking_glasses:

#19

@Cole, I’m with everyone. I don’t think anyone is criticizing you and we all only want you to give yourself some grace.

Someone else could look the same choice very differently. A different person could have said, oh no, I drank diet soda at those parties. Why oh why did I choose that instead of beer. Diet sodas are not healthy, so I chose the one that had no upside.

If you had never tried it, you might feel you missed out on something when you were older… now you know exactly what it feels like… better than trying it when you are older and then taking 10x longer to recover :slight_smile:

I rarely drink anymore.

To @A_User ’s point, I take LDN and that great glass of red with a meal no longer tastes as good. I was already drinking less often because Oura has shown me what it does to my sleep. It’s been interesting to see how many mocktails have suddenly appeared on menus.

And, like @desertshores, I’ve also done it all with no regrets. I have nothing left to get out of my system. The fact that I’m still alive might shock some people from my youth :).

Cole, I understand you have regret, but I promise you that you are not going to find many, if any, scientists worth their salt who feel consuming alcohol a couple of times causes harm. I am guessing they would feel the same about if someone smoked cigarettes a few times or had a few slices of cheesecake. Most will say it’s the habits that matter for your long term health, not the one offs.

You remember vividly how it felt.
If it gives you comfort, remembering how great something was, even if it was not wise to do, is part of one’s memories of a life well lived. I’ve jumped out a plane, had some naughty food, and “ahem” have done other unwise things I won’t list here… I only look back fondly and have no regrets.

I hope you can one day look back on your experiences with much kinder eyes, even if not health promoting and even if regrettable

3 Likes
#20

In the spirit of providing another data point. I am in a clinical trial that required three months on Rapamycin with twice monthly blood levels. Long story short .5 mg MWF put me just over their max target - 10ng/ml. Be careful folks, might be prudent to test more than here and there at first.

3 Likes
#21

@dajs
I strongly disagree with your post, especially posting it in the Lest We Off Ourselves thread.

What target? I am not sure what you are implying. Yes, some people experience things such as mouth sores, but they are in the minority, as Dr. Green’s evaluation of 333 adults shows.

There are no known deaths or any other irreversible side effects even from massive doses of rapamycin. If you know of any, please post the citations or papers.
(All bold type are mine):

I understand where you are coming from, as Dr. Mikail Blagosklonny said:

“But the fear of nonexistent side effects is not the only reason the use of mTOR inhibitors for life extension has been questioned. The second reason is that there is rightful skepticism about any claims made about anti-aging drugs because thousands of anti-aging remedies have already failed. What then makes rapamycin different?”

“However, numerous studies in mice show that late-life treatment extends lifespan. For example, when started at the age of 20 months, transient (for 90 days) treatment with high-dose rapamycin was sufficient to increase life expectancy by 60%.”

Brian Kennedy (Buck Insitute for Research on Aging, USA) " Rapamycin, a specific mTOR inhibitor confers robust extension of lifespan and healthspan in mice"

Mikhail V. Blagosklonny (Roswell Park Cancer Institute, Buffalo, USA): “In a number of experiments, rapamycin suppressed and slowed down cellular senescence of human cells. The mTOR inhibitor rapamycin prevents age-related weight gain, decreases rate of aging, increases life span and decreases carcinogenesis in mice.”

Vladimir Anisimov (N.N. Petrov Research Institute of Oncology, Russia):

"The mTOR inhibitor rapamycin prevents age-related weight gain, decreases rate of aging, increases life span and decreases carcinogenesis in transgenic HER-2/neu cancer-prone mice. Rapamycin dramatically delayed tumors onset, decreased a number of tumors per animal and tumor size. Lifelong administration of rapamycin extends lifespan in female 129/Sv mice.

“Importantly, rapamycin was administrated inter-mittently (every other 2 weeks) starting from the age of 2 months.”

Rapamycin inhibited age-related weight gain, decreased aging rate, increased lifespan (especially in the last survivors), and delayed spontaneous cancer."

"We envision that mTOR inhibitors may potentially be used to prevent sunlight-caused tumors as well as skin photo-aging.

Elimination of Proliferating Cells Unmasks the Shift from Senescence to Quiescence Caused by Rapamycin: Olga V Leontieva 1, Zoya N Demidenko 1, Andrei V Gudkov 1, Mikhail V Blagosklonny 1,*

Evaluation of off-label rapamycin use to promote healthspan in 333 adults

Green, Kaeberlein et al.

I didn’t participate in the study, but this is where I would fall, 18 mg or more equivalent once-weekly doses for 5 years.

image
image1433×910 82.3 KB

Despite these limitations, we find no evidence for significant increases in health risks, other than mouth sores, from off-label rapamycin use. A trend toward increased risk of bacterial and fungal infection was associated with rapamycin use, but did not reach statistical significance and appear to be small in magnitude. Overall, the risk of side effects from off-label use of rapamycin may compare favorably with other drugs commonly used off-label, such as statins [63] and metformin

A similar conclusion was reached by a study of rapamycin use in obesity [112]. It was suggested in 2008 that a pulse (intermittent) schedule of rapamycin administration would improve regeneration of stem cells [114] while avoiding mTORC2 inhibition [54,115].

This is what I follow and have had excellent results. Complete elimination of chronic actinic keratosis and no squamous or basal cell carcinomas since I started rapamycin.

This is my mantra. Not suggesting it for anyone else, especially young people:

Optimal dose of rapamycin for maximal net benefits. Life extension by rapamycin is dose-dependent in rodents. The higher the dose, the higher the anti-aging benefits, including cancer prevention and life extension. In humans, side effects are dose-dependent and net benefits could potentially decrease at very high doses. This point of the highest net benefit is the optimal dose. The optimal dose varies in different individuals due to the variability of potential side effects. Thus, the optimal dose in a particular individual is determined by the emergence of side effects. The treatment can be viewed as life-long phase I/II clinical trial.

image
image1328×1104 102 KB

2 Likes