How Do You Formulate Your Risk/Benefit Equation for Taking Supplements?

#1

I’m still new to this group but it looks like we have a pretty good age distribution, a high level of health awareness, and for many among us, rapamycin is but one among many supplements we take to improve our health and longevity.

Now in my 70s, I have been taking nutritional supplements since I was 24, adding and dropping supplements or changing doses along the way as the profile of evidence changed over the years. Those of you who were taking supplements around the time I started know how little good research there was to inform risk/benefit decisions.

Nonetheless, it was possible to find research that supported mostly rational decisions about whether to take a specific supplement. One of my informal decision rules at that time was to weigh downside risk much more heavily on upside benefit. I was not averse to taking a supplement for which the benefit was probable but as yet unproven, but I avoided supplements where the evidence of risk was stronger, irrespective of the benefits. (Of course, price and my budget figured in someplace.)

Now, some 50 years later, even though the number of supplements I take has expanded from a half dozen to five times that, my basic decision criteria have not changed substantially, with one exception. That exception is rapamycin. As a longevity drug, the list of probable benefits to someone my age is growing and they are significant. However, I’m not certain evidence for any of those probable benefits has crossed the line of generalized certainty based on large-n, multi-trait/multi-method (including randomized case control) evidence such as we have for many supplements. The risks of taking rapamycin, some of them at least, are clearer, albeit often derived from a different use of the drug. One somewhat theoretical risk I personally wonder about is if rapamycin might unfavorably tip a delicate balance of power between my immune system’s successful battle with a few nascent cancer cells of which I am unaware.

How do others formulate their risk/benefit decisions? Have you altered your general approach to making these decisions when it comes to taking rapamycin? I have changed my standards, I think, because the probable benefits seem more important to me at my age. If I were 25 years younger, I think I would be on the sidelines until we had at least a little more human evidence. Are others in our group still waiting and watching?

6 Likes
#2

Hi Rob, I’m 70 and like you have been interested in diet and health since I was young. I read Adele Davis ( Let’s Eat Right to Keep Fit (1954) and Let’s Get Well (1965)) when I was a teenager. I also was briefly on a Macrobiotic diet in high school because I wanted to be a Buddhist (deadly nightshade scared me). I still think of the Yin/Yang symbol when I think of the cycling of mTOR, on and off.
I’m also a long time supplement user, mine went from a couple to a whole bunch a couple of years ago. I’ve been fine tuning them and feel like my health is very good. But I’ve done a lot of reading, here and all over the internet, and decided to start rapamycin. I started taking Metformin 2 years ago because I thought that the preponderance of evidence showed that the risk/reward ratio was worth it. I take 850mg at night and feel no effects. I’m careful and am preparing to take a full battery of tests before (and after) starting rapamycin. I’ll start at a low dose (1mg/week) to start and then move up. I doubt I’ll ever go higher than 5-6 mg/week just because I tend to be conservative on dosing in general and my body seems sensitive. I’m hoping to see good results but from reading here it’s certainly possible that I won’t see any. But I think it’s worth a try.

4 Likes
#3

It’s a great question. To avoid the polypharmacy problem, I limit myself to 10 chemical interventions each week (with 1 day of zero chemicals each week). I don’t count food or dried food or spices / herbs or food powders (protein powder, moringa, wheatgerm, etc). If I find a new compelling chemical that I want to experiment with, I have to drop something from my list. I find that if I don’t have hard limits, I’ll slide back to the 30+ chemicals I was taking everyday previously.

Pharmaceuticals I pick to address issues with my blood markers (apoB, HbA1c are my targets). I go for drugs shown to also have longevity benefits. Aside from rapa I wouldn’t take a pharmaceutical just because it extended the lifespan of a mouse. And for supplements, I mostly think they don’t do much so missing out on “a great one” because I limit myself won’t matter compared to lifestyle factors.

Good luck

5 Likes
#4

Excellent questions. I view longevity as a marathon with hurdles or obstacles (like arteriosclerosis, dementia, diabetes, cancer, inflammation, etc…). Any medication or supplement that can help me clear a hurdle or obstacle gets added to my stack. For instance, all of the data from Rapamycin leads me to believe it helps with almost all obstacles so I added it. Based on my blood tests, I need a little help with my LDL and ApoB, so I added Bempedoic Acide + Ezetimibe. My HBA1C was trending higher so I added Metformin which is also synergistic with Rapamycin. I wanted to prevent cognitive decline and dementia, so I added Lithium Orotate, etc…

If there is a strong detriment or side effect, then that medication or supplement gets removed. For instance, I took Rosuvastatin (5 mg) for a few days and developed intense muscle soreness. I tried EOD, but no luck. Finally, I gave up after 2 weeks.

I hope this helps…

2 Likes
#5

This is a great discussion and a reminder of the strength of our small community. Even though our paths differ, the sharing feels good. Thank you @ng0rge, @Joseph_Lavelle, @DeStrider.

I still recall reading every one of the Adele Davis books. She was one of the very few pioneers who sought to develop an integrated perspective on nutrition and health. I also recall how the medical community and popular press considered her early death proof that her views were worthless. That was an early insight into their limitations. I’ll share others when time permits.

The problem of supplement overload, polypharmacy, liver health, etc. is always on my mind. I don’t have as much of a solution as a strategy. I classify my supplements for potential risk, potential benefit (all based on empirical research favoring quality research), degree of concentration, and a few other variables such as how closely they are related to my weak areas. As for concentration, my concern is low for supplements such as my daily dose of 5 mg. L-Ergothioneine which I could obtain in my diet. I review these at least annually based on current research. I review higher concentration supplements – such as concentrated curcumin, metformin, or ezetimibe – at least twice yearly to see if their inclusion remains justified. At present, rapamycin is the only “supplement” that I re-consider with each alternate week dose. Most weeks, I take at least one day off from most supplements.

While I take some supplements as research-based articles of faith, I have been able to get hard metrics on the benefits of other supplements. Astaxanthin is an example. My hsCRP has never been above 3.0 in the 15 years I have measured it but, through diet, I was able to reduce it to a consistent range between 0.5 and 0.9. After that, a research paper convinced me to add astaxanthin to my supplement stack to see if I could lower it further. I did and my level is now consistently less than 0.3. A good place to stop, I think.

Even though some research suggests little benefit at my age, my current goals are to lower my Apo(b) and my SHBG in ways (for Apo(b)) that do not involve statins. I tried them and cannot put up with the muscle pain and dysfunction. I also have genetically low LDH that runs 15-20% below the lower acceptable boundary and has for decades. For some, these low levels causes muscle pain or weakness but it has not for me. I ran 10Ks and marathons for four decades with no weakness or pain and generally placed near the top of my age division. I’m not optimistic about reducing or eliminating this deficiency.

I fully accept that the relevant efficacy of my supplement mix could range from slightly negative to significantly positive and that a few supplements might be a complete waste of money. Such is the risk of this kind of approach and I try to remember that in evaluation science, the last question to be asked and answered is, “Compared to what?”

I’m happy to share further if anyone has questions about my stack or has suggestions to share related to my current goals.

5 Likes
#6

@RobTuck If you’d like, you can share your stack here and open it up for constructive comments. It’s always good to look at what others are doing. There’s a topic all about What is your supplement stack.

3 Likes
#7

That is good to hear. Can you share more on what dose, how long did you take it for CRP to come down? Was anything else involved that could have drifted the effect instead? Did you test with

SHBG

This one may actually not be bad to have on the high side. It might be an example of healthspan perhaps suggesting low is better, but longevity suggesting that high actually is better.

There is one thread on this where I shared a lot of papers and reasons for such a read.

(It’s a bit similar to how higher testosterone, mTOR, Growth Hormone/IGF-1, protein intake, etc might be pro short/medium term healthspan but not pro long term healthspan/maximal longevity).

2 Likes
#8

@Neo ,

Thank you for the tip on SHBG. I’ll follow up and hope for a brighter outlook.

On Astaxanthin, as is usually the case with these N=1 inferences, it is not possible to be certain. What I am reasonably certain of is that my supplement regimen did not change in ways that might explain the effect over the period of interest. I usually obtain a comprehensive panel once or twice a year. Prior to initiating astaxanthin, I had hsCRP readings in the 0.9-0.5 range. My next reading, about a year later, was 0.29. Part of this period spanned Covid where I minimized testing, which might further reduce confidence. If you decide to try astaxanthin, I recommend the natural form (Bio-astin is good and Costco puts it on sale periodically – right now I think). The profile on the synthetic form is different.

Most of that time my dose was 12 mg. but for awhile I was taking 18 mg. Another unfortunate variable.

2 Likes
#9

Regarding supplements, here is some wisdom from George Ferman (who I’m still vetting but seems to be very well informed). This was echoed by Jeff Gladd MD of Fullscript in my interview with him (WiseAthletes).

Quote:

Then when it comes to supplements as we’ve stated multiple times, quality matters quite a lot.

Avoid any supplement with the following additives:

  1. Silicon dioxide

  2. Titanium dioxide

  3. Gums

  4. Artificial colorings such as red 40, blue 2, yellow 5

  5. Polyethylene

  6. Magnesium silicate

  7. Hydrogenated oils

https://journals.sagepub.com/doi/10.1177/07482337211058671?icid=int.sj-full-text.similar-articles.3

https://sciencedirect.com/science/article/pii/S0006291X2032091X

2 Likes
#10

I like the idea, but I though there were good gums. Do you know what his problem is with them?

1 Like
#11

Like you, I’ve been experimenting with supplements, macrobiotics and diet since my mid-20s (35 years) when my mom was diagnosed with metastatic lung cancer at age 44. Since then, following mainly the advice of Dr. Andrew Weil, I’ve taken many different supplements, adjusting along the way.

I started rapamycin in November, hoping it could help with an immune dysfunction first triggered by the Covid vaccine in 2021. It may help in the long run, but I found that 4-6 mg/wk exacerbated my inflammatory symptoms, so I’m taking a break now and will do 1 mg/wk when I try again.

It also occurred to me that the new inflammatory symptoms might have been caused by a combination of the rapamycin and the handfuls of supplements I took daily. My current view is that supplements can have effects and interact with each other and with medications in ways we don’t fully understand. So two weeks ago, I cut them to the bare minimum - multi, calcium (AKG), magnesium, nattokinase, aspirin, and vitamins B12, D, and K - and that’s all I’ll be taking when I restart the rapa along with metformin and a few necessary prescription meds.

2 Likes
#12

Yes. Good idea. In addition to keeping my list short I don’t take any supplements or medications on the weekends (a drug holiday) whether I take rapa or not. The only exception is metformin which i only take around my rapa dose (for now).

3 Likes
#13

I’m new to the idea of preservatives, binders, etc. in supplements, so I’m exploring …Here’s some info i found. Guar gum is mentioned. I think the issue is volume…if you are taking 30 pills and each one has preservatives, binders, etc. in them, you are getting a lot more than expected in your diet of pills.

Additives in Supplements: What are those odd ingredients? (Pt 1) – GreenTree Co-op Market.

1 Like
#14

I also take metformin and a few necessary prescription meds.

1 Like
#15

Here is more information from the FullScript website.

https://fullscript.com/blog/dietary-supplement-quality-guide

The part about “Excipients” I’ve copied here. They say they have a tool for putting in supplements to measure the “excipient” load.

Understanding excipients

In addition to full disclosure regarding allergens and ingredient sources, excipients can also impact the buying and prescribing decision, so full label transparency is required by the manufacturer. Excipients in dietary supplements, as well as pharmaceutical drugs, are therapeutically inactive ingredients added to aid in the manufacturing process, increase bioavailability, contribute to improved patient compliance, or to protect, support, or enhance product stability. (9)

While these added ingredients are considered inactive, they are not inert substances as some of these ingredients can interact with other ingredients in the formulation or lead to adverse or hypersensitivity reactions in patients. (11)

The FDA requires that excipients comply with food additive regulations or they have GRAS status, which stands for Generally Regarded as Safe. (29) There are a variety of different types of excipients that can be derived from natural or synthetic sources. Natural excipients come from plant, animal, or mineral sources and are considered less toxic compared to synthetic excipients. (16)

Here are some examples of the various types of natural excipients:

  • Fillers: plant cellulose, gelatin, lactose, sucrose, glucose
  • Binders: acacia, alginic acid, corn starch, alginate, polymers
  • Coating agents: gelatin, arabi, natural polymers
  • Lubricants: castor oil, mineral oil, paraffin oil
  • Preservatives: clove oil, cinnamon, turmeric, cocoa
  • Flavorings: ginger, raspberry, lemon, orange, peppermint
  • Colorings: caramel, chlorophylls, carotenoids, red beetroot, turmeric, saffron
  • Solvents: purified water, oils
  • Buffering agent: lemon juice
  • Emulsifying agents: acacia gum, gum ghatti

Common synthetic excipients include cellulose, dyes, magnesium stearate, parabens, and silicon dioxide. It’s important to clarify what role excipients are playing and that the manufacturer is not using excipients simply as fillers.

Excipients in dietary supplement products should be evaluated on risk to benefit ratio with a leaning toward natural excipients whenever possible.

2 Likes