Which supplements do you think are still worth taking?

Supplements
#101

Omega 3, through Nordic Naturals or a prescription Omega 3 such as Lovaza.

2 Likes
#102

How much Glycin are you taking? I also stopped taking NAC and continue with Glycin only.

#103

Thanks for that, @NakedMoleRat — helpful.

Regarding GlyNAC, I’m taking 6g glycine and 100mg NACET (which should be equivalent to something between 950mg to 1.9g of NAC due to supposed bioavailability) for three months (and half that for the prior four months) and I feel zero. A few on this forum have suggested that (at 53 and in pretty decent shape) I may not yet have a deficit, hence the zero impact.

#104

I take about 8 g/day dissolved in water. Yes it is quite confusing regarding the NAC. It is probably helpful for most things, but it seems the body needs the damage signal caused by ROS/RNS to activate oncogenes to fight cancer and the fact that one study shows it causes osteoarthritis in the knees (fourfold increase) is also worrying. I am going to try to look into it again but that will not make the bad studies go away :slight_smile:

3 Likes
#105

Huh. I missed that study, @NakedMoleRat . (I assume this is the study? Increased risk of knee osteoarthritis in patients using oral N-acetylcysteine: a nationwide cohort study - PMC )… I’ve been noticing over the past several months that my knees are a bit sore, but assumed it was from heavy weightlifting (a new practice four months ago) I’m now curious if I stopped NAC for six months would it go away? — I’m getting zero benefit from it anyway.

Huh.

1 Like
#106

I believe that when people feel zero benefit they may have enough of whatever they are supplementing. So feeling nothing may be a good sign (unless you feel bad all the time). It may be that you have very low levels of ROS and inflammation and do not need the extra glutathione, but I do as well and have recently had my hsCRP tested and it is essentially undetectable. Unfortunately I do not know what it was before taking Glynac. As I said in another comment it is unclear if boosting glutathione is always a good thing. It seems to be fairly well known in the world of medical research that extra glutathione boosts cancer cells while at the same time reducing senescent cells which sort of makes sense.

2 Likes
#107

Yes that is the one. Need to look into it more.

#108

Thank you, @Joseph . I started with the scientific papers. As I mentioned earlier: “There’s a great deal of studies on it but little practical information as far as I see. I’ve gone through a bunch of papers on it and it sounds like there are very very few human trials, a few animal trials, and a wide number of cell culture/in vitro studies of function.”

I was wondering if I missed a major paper or clinical trial. From your post, I’m feeling that I haven’t missed anything meaningful. Interestingly, I missed the increased knee atheroaethritis with NAC so just a concrete recent case where I whiffed.

#109

Yes, but if you have pre-existing kidney problems, creatine will raise your creatinine and send your kidneys into a tailspin.

1 Like
#110

no it will just increase creatinine and your kidney function will appear worse. I couldn’t find anything creatinine actually causes kidney damage, it’s just a marker

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#111

FWIW in a recent podcast (dated Nov 10, 2022. ‎Huberman Lab: Dr. Layne Norton: The Science of Eating for Health, Fat Loss & Lean Muscle on Apple Podcasts) I heard Dr. Layne Norton (About Layne Norton | Biolayne) state in the middle that the creatine/kidney damage theory has been “debunked”. But no further discussion.

1 Like
#112

A few articles I found on creatine and kidney health (in no particular order).

I must admit, after reviewing these papers (some clinical trials, some meta-analyses, and “literature reviews” (how does that merit a paper?) I am starting to think that even with one kidney — as long as it has healthily function (which it is), and I am healthy (which I am) — that creatine could be a benefit in building muscle, and possibly other impacts such as cardiovascular health, etc. Not using “bro-science” dosing (like the 20g per day I’ve seen, and higher), but long term 4g per day could be safe.

Does this make sense?

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Long-term creatine supplementation is safe in aged patients with Parkinson disease

Andreas Bender et al. Nutr Res. 2008 Mar.

The food supplement creatine (Cr) is widely used by athletes as a natural ergogenic compound. It has also been increasingly tested in neurodegenerative diseases as a potential neuroprotective agent. Weight gain is the most common side effect of Cr, but sporadic reports about the impairment of renal function cause the most concerns with regard to its long-term use. Data from randomized controlled trials on renal function in Cr-supplemented patients are scarce and apply mainly to healthy young athletes. We systematically evaluated potential side effects of Cr with a special focus on renal function in aged patients with Parkinson disease as well as its current use in clinical medical research. Sixty patients with Parkinson disease received either oral Cr (n = 40) or placebo (n = 20) with a dose of 4 g/d for a period of 2 years. Possible side effects as indicated by a broad range of laboratory blood and urine tests were evaluated during 6 follow-up study visits. Overall, Cr was well tolerated. Main side effects were gastrointestinal complaints. Although serum creatinine levels increased in Cr patients because of the degradation of Cr, all other markers of tubular or glomerular renal function, especially cystatin C, remained normal, indicating unaltered kidney function. The data in this trial provide a thorough analysis and give a detailed overview about the safety profile of Cr in older age patients.

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Does Creatine Supplementation Affect Renal Function in Patients with Peripheral Artery Disease? A Randomized, Double Blind, Placebo-controlled, Clinical Trial

Wagner Jorge Ribeiro Domingues et al. Ann Vasc Surg. 2020 Feb.
Results: No significant differences were found between groups before and after the intervention for serum creatinine (Cr: pre 1.00 ± 0.15 mL/dL vs. post 1.07 ± 0.16 mL/dL; PLA: pre 1.30 ± 0.53 mL/dL vs. post 1.36 ± 0.47 mL/dL, P = 0.590), creatinine excretion rate (Cr: pre 81.73 ± 43.80 mg/dL vs. post 102.92 ± 59.57 mg/dL; PLA: pre 74.37 ± 38.90 mg/dL vs. post 86.22 ± 39.94 mg/dL, P = 0.560), or creatinine clearance (Cr; pre 108 ± 59 mL/min/1.73 m2 vs. post 117 ± 52 mL/min/1.73 m2; PLA: pre 88 ± 49 mL/min/1.73 m2 vs. post 82 ± 47 mL/min/1.73 m2, P = 0.366).

Conclusions: Eight weeks of creatine supplementation is safe and does not compromise the renal function of patients with peripheral arterial disease

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Effects of creatine supplementation on renal function: a randomized, double-blind, placebo-controlled clinical trial

Bruno Gualano et al. Eur J Appl Physiol. 2008 May.

Creatine (CR) supplementation is commonly used by athletes. However, its effects on renal function remain controversial. The aim of this study was to evaluate the effects of creatine supplementation on renal function in healthy sedentary males (18-35 years old) submitted to exercise training. A randomized, double-blind, placebo-controlled trial was performed. Subjects (n = 18) were randomly allocated to receive treatment with either creatine (CR) ( approximately 10 g day(-1) over 3 months) or placebo (PL) (dextrose). All subjects undertook moderate intensity aerobic training, in three 40-min sessions per week, during 3 months. Serum creatinine, serum and urinary sodium and potassium were determined at baseline and at the end of the study. Cystatin C was assessed prior to training (PRE), after 4 (POST 4) and 12 weeks (POST 12). Cystatin C levels (mg L(-1)) (PRE CR: 0.82 +/- 0.09; PL: 0.88 +/- 0.07 vs. POST 12 CR: 0.71 +/- 0.06; PL: 0.75 +/- 0.09, P = 0.0001) were decreased over time, suggesting an increase in glomerular filtration rate. Serum creatinine decreased with training in PL but was unchanged with training in CR. No significant differences were observed within or between groups in other parameters investigated. The decrease in cystatin C indicates that high-dose creatine supplementation over 3 months does not provoke any renal dysfunction in healthy males undergoing aerobic training. In addition, the results suggest that moderate aerobic training per se may improve renal function.

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Potential Adverse Effects of Creatine Supplement on the Kidney in Athletes and Bodybuilders

Dorna Davani-Davari et al. Iran J Kidney Dis. 2018 Oct.
Results: Short- and long-term creatine supplementations (range, 5 days to 5 years) with different doses (range, 5 g/d to 30 g/d) had no known significant effects on different studied indexes of kidney function such as glomerular filtration rate at least in healthy athletes and bodybuilders with no underlying kidney diseases. In addition, although short-term (range, 5 days to 2 weeks) high-dose oral creatine supplementation (range, 20 g/d to 0.3 g/kg/d) stimulated the production of methylamine and formaldehyde (as potential cytotoxic metabolites of creatine) in the urine of healthy humans, there was currently no definite clinical evidence about their adverse effects on the kidney function.

Conclusions: Although creatine supplementation appears to have no detrimental effects on kidney function of individuals without underlying kidney diseases, it seems more advisable to suggest that creatine supplementation not to be used by sportsmen or women with pre-existing kidney disease or those with a potential risk for kidney dysfunction.

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Adverse effects of creatine supplementation: fact or fiction?

J R Poortmans et al. Sports Med. 2000 Sep.

The consumption of oral creatine monohydrate has become increasingly common among professional and amateur athletes. Despite numerous publications on the ergogenic effects of this naturally occurring substance, there is little information on the possible adverse effects of this supplement. The objectives of this review are to identify the scientific facts and contrast them with reports in the news media, which have repeatedly emphasised the health risks of creatine supplementation and do not hesitate to draw broad conclusions from individual case reports. Exogenous creatine supplements are often consumed by athletes in amounts of up to 20 g/day for a few days, followed by 1 to 10 g/day for weeks, months and even years. Usually, consumers do not report any adverse effects, but body mass increases. There are few reports that creatine supplementation has protective effects in heart, muscle and neurological diseases. Gastrointestinal disturbances and muscle cramps have been reported occasionally in healthy individuals, but the effects are anecdotal. Liver and kidney dysfunction have also been suggested on the basis of small changes in markers of organ function and of occasional case reports, but well controlled studies on the adverse effects of exogenous creatine supplementation are almost nonexistent. We have investigated liver changes during medium term (4 weeks) creatine supplementation in young athletes. None showed any evidence of dysfunction on the basis of serum enzymes and urea production. Short term (5 days), medium term (9 weeks) and long term (up to 5 years) oral creatine supplementation has been studied in small cohorts of athletes whose kidney function was monitored by clearance methods and urine protein excretion rate. We did not find any adverse effects on renal function. The present review is not intended to reach conclusions on the effect of creatine supplementation on sport performance, but we believe that there is no evidence for deleterious effects in healthy individuals. Nevertheless, idiosyncratic effects may occur when large amounts of an exogenous substance containing an amino group are consumed, with the consequent increased load on the liver and kidneys. Regular monitoring is compulsory to avoid any abnormal reactions during oral creatine supplementation.

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The effect of creatine intake on renal function

Kurt A Pline et al. Ann Pharmacother. 2005 Jun.
Data synthesis: Supplementation with creatine, an unregulated dietary substance, is increasingly common in young athletes. To date, few studies have evaluated the impact of creatine on renal function and estimates of creatinine clearance. Because creatine is converted to creatinine in the body, supplementation with large doses of creatine may falsely elevate creatinine concentrations. Five studies have reported measures of renal function after acute creatine ingestion and 4 after chronic ingestion. All of these studies were completed in young healthy populations. Following acute ingestion (4-5 days) of large amounts of creatine, creatinine concentrations increased slightly, but not to a clinically significant concentration. Creatinine is also only minimally affected by longer creatine supplementation (up to 5.6 y).

Conclusions: Creatine supplementation minimally impacts creatinine concentrations and renal function in young healthy adults. Although creatinine concentrations may increase after long periods of creatine supplementation, the increase is extremely limited and unlikely to affect estimates of creatinine clearance and subsequent dosage adjustments. Further studies are required in the elderly and patients with renal insufficiency.

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Few adverse effects of long-term creatine supplementation in a placebo-controlled trial

G J Groeneveld et al. Int J Sports Med. 2005 May.

Although oral creatine supplementation is very popular among athletes, no prospective placebo-controlled studies on the adverse effects of long-term supplementation have yet been conducted. We performed a double-blind, placebo-controlled trial of creatine monohydrate in patients with the neurodegenerative disease amyotrophic lateral sclerosis, because of the neuroprotective effects it was shown to have in animal experiments. The purpose of this paper is to compare the adverse effects, and to describe the effects on indirect markers of renal function of long-term creatine supplementation. 175 subjects (age = 57.7 +/- 11.1 y) were randomly assigned to receive creatine monohydrate 10 g daily or placebo during an average period of 310 days. After one month, two months and from then on every fourth month, adverse effects were scored using dichotomous questionnaires, plasma urea concentrations were measured, and urinary creatine and albumin concentrations were determined. No significant differences in the occurrence at any time of adverse effects due to creatine supplementation were found (23 % nausea in the creatine group, vs. 24 % in the placebo group, 19 % gastro-intestinal discomfort in the creatine group, vs. 18 % in the placebo group, 35 % diarrhoea in the creatine group, vs. 24 % in the placebo group). After two months of treatment, oedematous limbs were seen more often in subjects using creatine, probably due to water retention. Severe diarrhoea (n = 2) and severe nausea (n = 1) caused 3 subjects in the creatine group to stop intake of creatine, after which these adverse effects subsided. Long-term supplementation of creatine did not lead to an increase of plasma urea levels (5.69 +/- 1.47 before treatment vs. 5.26 +/- 1.44 at the end of treatment) or to a higher prevalence of micro-albuminuria (5.4 % before treatment vs. 1.8 % at the end of treatment).

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4 Likes
#113

This was mentioned in one of the papers I linked to (and pasted abstracts) in my just-prior post: young-ish (18-35 yr old) makes undergoing “moderate exercise” (likely less than most on this forum) “ Serum creatinine decreased with training in PL (placebo) but was unchanged with training in CR (creatine supplementation).

In the other papers they mention no change in renal function. Maybe I cherry-picked papers accidentally, but if you have other papers that suggest creatine supplementation decreases kidney function: I’d LOVE to read them (I am trying to be as safe as I can with one kidney).

The paper is below, and don’t forget the many other I linked to in my just-prior post.

Effects of creatine supplementation on renal function: a randomized, double-blind, placebo-controlled clinical trial

Bruno Gualano et al. Eur J Appl Physiol. 2008 May.

Creatine (CR) supplementation is commonly used by athletes. However, its effects on renal function remain controversial. The aim of this study was to evaluate the effects of creatine supplementation on renal function in healthy sedentary males (18-35 years old) submitted to exercise training. A randomized, double-blind, placebo-controlled trial was performed. Subjects (n = 18) were randomly allocated to receive treatment with either creatine (CR) ( approximately 10 g day(-1) over 3 months) or placebo (PL) (dextrose). All subjects undertook moderate intensity aerobic training, in three 40-min sessions per week, during 3 months. Serum creatinine, serum and urinary sodium and potassium were determined at baseline and at the end of the study. Cystatin C was assessed prior to training (PRE), after 4 (POST 4) and 12 weeks (POST 12). Cystatin C levels (mg L(-1)) (PRE CR: 0.82 +/- 0.09; PL: 0.88 +/- 0.07 vs. POST 12 CR: 0.71 +/- 0.06; PL: 0.75 +/- 0.09, P = 0.0001) were decreased over time, suggesting an increase in glomerular filtration rate. Serum creatinine decreased with training in PL but was unchanged with training in CR. No significant differences were observed within or between groups in other parameters investigated. The decrease in cystatin C indicates that high-dose creatine supplementation over 3 months does not provoke any renal dysfunction in healthy males undergoing aerobic training. In addition, the results suggest that moderate aerobic training per se may improve renal function.

1 Like
#114

For the elderly creatine supplementation seems to help prevent sarcopenia.

“Overall, creatine brought beneficial effects for the prevention of
sarcopenia in elderly individuals”

“Effects of creatine supplementation in the prevention of sarcopenia”

5 Likes
#115

Take a look at this thread!

3 Likes
#116

Is that thread an advertisement for Nootropicsdepot?

3 Likes
#117

I am taking most of the supplements listed by Dr. Sinclair. I would also hazard a guess he is also taking Rapamycin secretly. It’s hard to be in the longevity field and not take it.

I also take many of the ITP recommended supplements such as acarbose, Astaxanthin, and glycine (at much higher dosages). I am not sure why Sinclair wouldn’t be taking these…

1 Like
#118

Trouble is with David Sinclair’s stack is that key components of it (Reseveratrol, NAD boosters) have not shown any benefits in lifespan by the NIA ITP… See below:

NAD Promoters / Resveratrol Supplementation

The only other thing I’d note is that with regard to the NAD / Resveratrol supplement - that if you take it and it makes you feel better then thats fine - I’ve not seen any literature to suggest those compounds will harm you.

However, in terms of cost-effectiveness of NAD boosters and Resveratrol they have a very mixed history in terms of their effectiveness in terms of longevity increases and I don’t take it because I don’t think the results indicated by the research and that I experienced when trying them (no obvious benefit in either situation) justify the high price. Rapamycin has decades of research, and is quite inexpensive by comparison.

NAD boosters failed to increase lifespan at all in the best, long term study (The National Institutes of Aging Intervention Testing Program run by Richard Miller) that has been done on Nicotinomide Riboside (the most popular NAD booster), as can be seen in this paper: 17‐a‐estradiol late in life extends lifespan in aging UM‐HET3 male mice; nicotinamide riboside and three other drugs do not affect lifespan in either sex - PMC

I also recommend you listen to this podcast where Matt Kaeberlein talks about these compounds: NAD and NAD precursors: help or hype? | Peter Attia, M.D. & Matt Kaeberlein, Ph.D. - YouTube

In another podcast for his subscribers on this topic, here are some points they make:

NAD precursors :

  • Having said that NAD and the intermediates in the NAD biosynthesis and breakdown pathways are highly interconvertible
  • This is something that is emerging, that our cells are really quite able to take up precursors of NAD in that NAD pathway.
  • There could be a salvage pattern here where if you give somebody intravenous NAD, it’s possible that they’re turning it into NMN or NR… and then right back to NAD in the cell, if the NMN or NR gets transported into the cell
  • People are studying NAD precursors (nicotinamide riboside and nicotinamide mononucleotide) primarily in the context of aging
  • There are still real questions around the efficacy with which those molecules are taken up through the gut once they get into circulation taken into cells
  • But there are other NAD metabolites like nicotinamide, which can be interconverted
  • What seems to be the case is that even when you treat with, say an NAD cursor, it may not get into circulation as those molecules, but they can be interconverted in circulation or in cells
  • The real questions are:
    • 1 – Do those molecules have a big effect on NAD homeostasis and NAD levels in cells and tissues?
    • 2 – Do we see functional improvements in those cells and tissues that then you would predict would turn into improved health span, potentially increased lifespan in laboratory animals?

What’s with all the hype?

  • Two molecules, NR and NMN
  • These are orally bioavailable
  • They are safe from an acute toxicity standpoint, there’s not anything that one needs to be concerned with here
  • These are over the counter supplements
  • For as much hype as there is around this, we really don’t have a lot of great data to point to that these things are improving lifespan

What does Matt Kaebelein make of this hype in the face of a lack of clear data?

  • This is the crux of the issue
  • When evaluating different interventions that potentially affect the biology of aging, Matt asks himself: What’s the best data that these things actually have a strong impact?
  • And in this particular case, when referring to normative aging…
    • we don’t want to be working in a short-lived background that has some specific pathology
    • And in this scenario, Matt is not confident that NR or NMN can increase lifespan in wild type mice

So what is the most compelling evidence?

Study by Zhang et al., 2016:

  • This study reported that late life administration of nicotinamide riboside in C57 black 6 mice had a small, but statistically significant effect on survival
  • As was noted in Figure 4 above, the controls in that experiment were shortlived and the experiments where the controls are shortlived, if the effect of the intervention small, that’s often not reproducible
  • And in this case, when the ITP attempted to test nicotinamide riboside, they saw no effect on lifespan or any other real phenotype
3 Likes
#119

They are testing NR + Metformin now at the ITP. So I guess there is still some interest.

3 Likes
#120

All such studies have been done on young, healthy males. Yes, these subjects showed a temporary but harmless increase in creatinine. It is an artifact of creatine consumption. However, it isn’t known if the same blase attitude is warranted for those with CKD, who have various degrees of reduced kidney function. I wouldn’t want to risk it, nor would I like to argue with my nephrologist about it.

1 Like