Jump to content

Recommended Posts

All,

 

Testosterone (T) and other sex hormone levels have always been a topic of interest and concern to CR practitioners. Some men (like me) report dramatically reduced T levels, down to levels not typically seen in any men except the very elderly. Others seem to maintain their T at fairly normal levels for their age.

 

So which is better?

 

On the one hand, low testosterone has sometimes been considered a CR "badge of courage" (among men anyway) - indicating one is practicing serious CR, and a positive reflection of the body trading off fecundity for upregulation of maintenance & repair functions (similar to low IGF-1). Women live longer than men across cultures, which some attribute to differences in T level, and eunuchs have been found to live longer, by as much as 15-20 years [2]! 

 

On the other hand, low T often (but not always) has a dramatic effect on libido, and one's overall aggressive drive to succeed / accomplish things. On the health side, negative health outcomes are frequently associated with hypogonadism (low T) in men, including bone health issues [4], sarcopenia [4], cognitive decline [5], and an increased risk of cardiovascular disease.

 

Regarding the latter, some studies (e.g. see [3] for review) have found T supplementation in hypogonadal men reduces cardiovascular disease risk, but the effect may be limited to obese men with metabolic syndrome, or may result from pharmaceutical industry bias in T supplementation trials [6]. Interestingly, this meta-analysis [6] found that in trials not sponsored by Big Pharma, CVD risk was increased among men receiving supplemental T (OR 2.06, 95% CI 1.34 to 3.17).

 

So overall, the relationship between the low T that many serious male CR practitioners exhibit and our long-term health & longevity remains an open question. Moreover, hypogonadism in the general population is typically associated with obesity and metabolic syndrome, obviously a very different etiology than hypogonadism in CR practitioners, making the picture even more muddled...

 

So I reacted with interest, but also some trepidation, when I saw Al Pater post this new study [1] (thanks Al!), on the association of T and other sex hormones with all-cause, cancer and cardiovascular mortality in men. So let's dive in.

 

First off, this was not a supplementation trial - they measured the natural levels of T, Luteinizing Hormone (LH), Follicle-Stimulating Hormone (FSH), Sex Hormone Binding Globulin (SHBG), free testosterone (FT), and estradiol (E) and in 5300 men of all ages and followed them for an average of 18.5 years to see how many died, from what causes, and how their deaths were associated with these sex hormones.

 

Here are some interesting statistics at baseline, from the free full text Table 1 (see below):

  • As expected, T and FT was lower in older men, whereas LH, FSH, and SHBG increased.
  • Interestingly, smokers had higher T, FT, LH, FSH, E and SHBG than non-smokers at baseline.
  • Exercise, and particular "competitive sport" participation, was associated with increased T, FT, and lower LH. Could be reverse causality - people with high T are more aggressive and therefore more likely to be attracted to competitive sports...
  • Overweight and obese men had dramatically lower T and FT at baseline - which will be important later.

Here is the baseline data for sex hormones by demographics for anyone interested in the details (click to enlarge):

 

post-7043-0-19822400-1445799634_thumb.jpg

 

Now the interesting part - the mortality results (some of which comes from the text of the supplemental material).

 

First for cancer mortality:

  • There was a between-quartile trend towards increased cancer mortality with higher T, but the differences was only really significant in smokers in the highest quartile of T (OR 1.53, 95%CI: 1.14 – 2.08).
  • In non-smokers, T and FT had virtually no impact on cancer mortality. But there was a pretty strong trend towards more cancer with higher levels of LH and FSH. Keep an eye on LH in particular, it will be important later...

And now, CVD mortality:

  • Men with total testosterone levels in the highest quartile had a reduced risk of CVD mortality compared to men in the lowest quartile (HR 0.72, 95% CI: 0.53– 0.98). The same relationship held for FT. It is looking bad for us hypogonadal CRers...
  • But this increased CVD risk with low T (and FT) was in the fully-adjusted model, which included factoring out BMI from the analysis (recall overweight/obese men had dramatically lower T and FT at baseline).
  • In a model that adjusted for waist circumference instead of BMI, and especially in a model that adjusted for # of markers of metabolic syndrome, the increased risk of CVD with lower T and FT dropped dramatically to the point of no longer being significant between the  highest and lowest quintiles of T = (OR 0.66, 95%CI: 0.38-1.16). In other words, to first approximations, if you ignore low T and FT resulting from (or associated with) metabolic syndrome, the association between low T (and FT) and increased CVD goes away...

And now, the all-important All-cause mortality:

  • There was no significant differences in all-cause mortality across age-standardized quartiles of T (OR 1.01, 95%CI: 0.87-1.18) - to some degree higher cancer risk and lower CVD risk with higher T offset each other, so all-cause mortality was a wash with higher T. The same lack of significant mortality effect was seen for inter-quartile comparison of FT (OR 0.87, 95%CI: 0.75-1.00), but when the trend from lowest to highest quartile of FT was considered, lower FT was associated with increased all-cause mortality (p for trend < 0.02). Again, looking (somewhat) bad for hypogonadal CRers...
  • An increased all-cause mortality was seen for men in the highest (vs. lowest) quartiles of LH and estradiol, (HR 1.32, 95% CI: 1.14 –1.53) and  (HR 1.23, 95% CI: 1.06 –1.43), respectively.

If you are confused by now, perhaps this graphical depiction of the major study findings for all-cause and CVD mortality (with my color highlights) will help (click to enlarge):

 

post-7043-0-60444400-1445803488_thumb.jpg

 

As you can see, if we focus on all-cause mortality, higher SHBG, higher LH, and lower FT are associated with increased risk.

 

So what the heck does all this mean?!?!

 

Here is my take on it, basically paraphrasing the authors' discussion / speculation. Obesity, and especially metabolic syndrome, are associated with increased mortality risk, and reduced T and FT levels. It may therefore be that low T (& FT) is a marker for impaired androgen signalling in men with metabolic syndrome - i.e. their sex-hormone signalling is messed up, just like some of their other pathways (e.g. insulin signalling) are messed up by all the fat they are carrying. As a result, their LH is elevated - i.e. the "captain" is asking (via increased LH) the "engine room" (i.e. Leydig cells) to produce more T, but the Leydig cells aren't up to the task perhaps because they are gummed up with fat, so T remains low despite elevated LH calling for more. This could be similar in some respects to diabetes, in which insulin doesn't work to clear glucose because of fat so the body calls for the pancreas to produce more, and eventually the beta cells in the pancreas give up the ghost and can't make enough insulin to clear blood glucose.

 

So what does this mean for CR practitioners?

 

In us, T is low on purpose from the body's perspective (if I may speak teleologically) - as indicated by our low LH levels (my bloodwork shows my LH to always be near or below the low end of the RR since starting CR). In other words, rather than T being low because the body can't/won't make it (as is the case in guys with metabolic syndrome), our T is low because our body doesn't need or want it.

 

Again it is perhaps a story similar to IGF-1 and insulin. We (hopefully) have low fasting insulin not because our beta cells are messed up and can't make it (like in late-stage diabetes resulting from metabolic syndrome), but because our bodies don't need/want much insulin - we've got enough insulin to clear the modest amount of glucose we have to process, especially since our insulin sensitivity remains high.

 

So in short, our low T and low FT may reflect an entirely different, (hopefully) healthier state to be in than having low T and FT as a result of metabolic syndrome.

 

But then again, that might be just wishful thinking. In particular, our low T and FT may be "intentional" on the part of our body and it may not be good for us in the long run. In other words, our bodies may be hunkering down to survive the (self-induced) famine by lowering T and FT, but in the process sacrificing "non-critical" systems like muscle mass, bone health, and cognitive function - systems that apparently benefit downstream from higher levels of testosterone.

 

It seems it could go either way. But in any case, we're unlikely to be in as bad shape along these dimensions as men who have low T and FT as a result of metabolic syndrome.

 

I hope this has done more to clarify than confuse. But re-reading, I'm not so sure...

 

--Dean

 

----------

[1] J Clin Endocrinol Metab. 2015 Oct 21:jc20152460. [Epub ahead of print]

 

The association of reproductive hormone levels and all-cause, cancer and cardiovascular disease mortality in men.

 

Agergaard Holmboe S, Vradi E, Kold Jensen T, Linneberg A, Husemoen LL, Scheike T, Skakkebæk NE, Juul A, Andersson AM.

Full Text: http://press.endocrine.org/doi/pdf/10.1210/jc.2015-2460

Abstract

CONTEXT:

Testosterone levels (T) have been associated with mortality, but controversy exists.

OBJECTIVE:

To investigate associations between serum levels of total testosterone, SHBG, free testosterone, estradiol, LH and FSH, and subsequent mortality with up to 30 years of follow-up.

DESIGN:

A prospective cohort study consisting of men participating in four independent population-based surveys (MONICA I-III and Inter99) from 1982 to 2001 and followed until December 2012 with complete registry follow-up.

SETTING AND PARTICIPANTS:

5,350 randomly selected men from the general population aged 30, 40, 50, 60 or 70 years at baseline.

MAIN OUTCOME MEASURES:

All-cause mortality, cardiovascular disease (CVD) mortality and cancer mortality.

RESULTS:

1,533 men died during the follow-up period; 428 from CVD and 480 from cancer. Cox proportional hazard models revealed that men in highest LH quartile had an increased all-cause mortality compared to lowest quartile (HR=1.32, 95%CI: 1.14 to 1.53). Likewise, increased quartiles of LH/T and estradiol increased the risk of all-cause mortality (HR=1.23, 95%CI: 1.06 to 1.43, HR=1.23, 95%CI: 1.06 to 1.43). No association to testosterone levels was found. Higher LH levels were associated with increased cancer mortality (HR=1.42, 95%CI: 1.10 to 1.84) independently of smoking status. Lower CVD mortality was seen for men with testosterone in the highest quartile compared to lowest (HR=0.72, 95%CI: 0.53 to 0.98). Furthermore, negative trends were seen for SHBG and free testosterone in relation to CVD mortality, however insignificant.

CONCLUSION:

The observed positive association of LH and LH/T, but not testosterone, with all-cause mortality suggests that a compensated impaired Leydig cell function may be a risk factor for death by all causes in men. Our findings underpin the clinical importance of including LH measurement in the diagnostic work-up of male patients seeking help for possible androgen insufficiency.

 

PMID: 26488309

 

------------

[2] Curr Biol. 2012 Sep 25;22(18):R792-3. doi: 10.1016/j.cub.2012.06.036.

The lifespan of Korean eunuchs.

Min KJ, Lee CK, Park HN.

 

Free Full Text: http://www.cell.com/current-biology/abstract/S0960-9822(12)00712-9

 

Abstract

 

Although many studies have shown that there are trade-offs between longevity and reproduction, whether such trade-offs exist in humans has been a matter of debate [1,2] . In many species, including humans, males live shorter than females, which could be due to the action of male sex hormones. Castration, which removes the source of male sex hormones, prolongs male lifespan in many animals, but this issue has been debated in humans [3] . To examine the effects of castration on longevity, we analyzed the lifespan of historical Korean eunuchs. Korean eunuchs preserved their lineage by adopting castrated boys. We studied the genealogy records of Korean eunuchs and determined the lifespan of 81 eunuchs. The average lifespan of eunuchs was 70.0 ± 1.76 years, which was 14.4–19.1 years longer than the lifespan of non-castrated men of similar socio-economic status. Our study supports the idea that male sex hormones decrease the lifespan of men.

 

PMID: 23017989

 

--------------

[3] Expert Opin Drug Saf. 2014 Oct;13(10):1327-51. doi: 10.1517/14740338.2014.950653.

Epub 2014 Aug 19.

Cardiovascular risk associated with testosterone-boosting medications: a
systematic review and meta-analysis.

Corona G(1), Maseroli E, Rastrelli G, Isidori AM, Sforza A, Mannucci E, Maggi M.

Author information:
(1)Azienda-Usl Bologna, Maggiore-Bellaria Hospital, Medical Department,
Endocrinology Unit , Bologna , Italy.

INTRODUCTION: Recent reports have significantly halted the enthusiasm regarding
androgen-boosting; suggesting that testosterone supplementation (TS) increases
cardiovascular (CV) events.
AREAS COVERED: In order to overcome some of the limitations of the current
evidence, the authors performed an updated systematic review and meta-analysis of
all placebo-controlled randomized clinical trials (RCTs) on the effect of TS on
CV-related problems. Out of 2747 retrieved articles, 75 were analyzed, including
3016 and 2448 patients in TS and placebo groups, respectively, and a mean
duration of 34 weeks. Our analyses, performed on the largest number of studies
collected so far, indicate that TS is not related to any increase in CV risk,
even when composite or single adverse events were considered. In RCTs performed
in subjects with metabolic derangements a protective effect of TS on CV risk was
observed.

EXPERT OPINION: The present systematic review and meta-analysis does not support
a causal role between TS and adverse CV events. Our results are in agreement with
a large body of literature from the last 20 years supporting TS of hypogonadal
men as a valuable strategy in improving a patient's metabolic profile, reducing
body fat and increasing lean muscle mass, which would ultimately reduce the risk
of heart disease.

PMID: 25139126

 

---------------

[4] Clin Endocrinol (Oxf). 2005 Sep;63(3):280-93.

Effects of testosterone on body composition, bone metabolism and serum lipid
profile in middle-aged men: a meta-analysis.

Isidori AM(1), Giannetta E, Greco EA, Gianfrilli D, Bonifacio V, Isidori A, Lenzi
A, Fabbri A.

Author information:
(1)Cattedra di Andrologia, Universita 'La Sapienza', Rome, Italy.
andrea.isidori@uniroma1.it

OBJECTIVES: Ageing in men is associated with a gradual decline in serum
testosterone levels and a concomitant loss of muscle mass, accumulation of
central adiposity, impaired mobility and increased risk of bone fractures.
Whether androgen treatment might be beneficial in these subjects is still under
debate. We have carried out a systematic review of randomized controlled trials
(RCTs) evaluating the effects of testosterone (T) administration to middle-aged
and ageing men on body composition, muscle strength, bone density, markers of
bone metabolism and serum lipid profile.
DATA SOURCE: A comprehensive search of all published randomized clinical trials
was performed using the MEDLINE, Cochrane Library, EMBASE and Current Contents
databases.
REVIEW METHODS: Guided by prespecified criteria, software-assisted data
abstraction and quality assessed by two independent reviewers, 29 RCTs were found
to be eligible. For each investigated variable, we reported the results of pooled
estimates of testosterone treatment using the random effect model of
meta-analysis. Heterogeneity, reproducibility and consistency of the findings
across studies were explored using sensitivity and meta-regression analysis.
RESULTS: Overall, 1,083 subjects were evaluated, 625 randomized to T, 427 to
placebo and 31 to observation (control group). Weighted mean age was 64.5 years
(range 49.9--77.6) and mean serum testosterone was 10.9 nmol/l (range 7.8--19).
Testosterone treatment produced: (i) a reduction of 1.6 kg (CI: 2.5--0.6) of
total body fat, corresponding to -6.2% (CI: 9.2--3.3) variation of initial body
fat, (ii) an increase in fat free mass of 1.6 kg (CI: 0.6--2.6), corresponding to
+2.7% (CI: 1.1--4.4) increase over baseline and (iii) no change in body weight.
The effects of T on muscle strength were heterogeneous, showing a tendency
towards improvement only at the leg/knee extension and handgrip of the dominant
arm (pooled effect size=0.3 standard mean difference (SMD), CI: -0.0 to 0.6).
Testosterone improved bone mineral density (BMD) at the lumbar spine by +3.7%
(CI: 1.0--6.4%) compared to placebo, but not at the femoral neck, and produced a
consistent reduction in bone resorption markers (pooled effect size = -0.6 SMD,
CI: -1.0 to -0.2).
Testosterone also reduced total cholesterol by 0.23 mmol/l
(CI: -0.37 to -0.10), especially in men with lower baseline T concentrations,
with no change in low density lipoprotein (LDL)-cholesterol. A significant
reduction of high density lipoprotein (HDL)-cholesterol was found only in studies
with higher mean T-values at baseline (-0.085 mmol/l, CI: -0.017 to -0.003).
Sensitivity and meta-regression analysis revealed that the dose/type of T used,
in particular the possibility of aromatization, explained the heterogeneity in
findings observed on bone density and HDL-cholesterol among studies.
CONCLUSION: The present analysis provides an estimate of the average treatment
effects of testosterone therapy in middle-aged men. Our findings are sufficiently
strong to justify further interventional studies focused on alternative targets
of androgenic treatment carrying more stringent clinical implications, in
particular the cardiovascular, metabolic and neurological systems.

PMID: 16117815

 

-------------

[5] Mol Neurobiol. 2015 Jul 8. [Epub ahead of print]

Low Testosterone Level and Risk of Alzheimer's Disease in the Elderly Men: a
Systematic Review and Meta-Analysis.

Lv W(1), Du N(1), Liu Y(1), Fan X(1), Wang Y(1), Jia X(2), Hou X(3), Wang B(4).

Sex steroids can positively affect the brain function, and low levels of sex
steroids may be associated with worse cognitive function in the elderly men.
However, previous studies reported contrary findings on the relationship between
testosterone level and risk of Alzheimer's disease in the elderly men. The
objective of this study was to comprehensively assess the relationship between
low testosterone level and Alzheimer's disease risk in the elderly men using a
meta-analysis. Only prospective cohort studies assessing the influence of low
testosterone level on Alzheimer's disease risk in elderly men were considered
eligible. Relative risks (RRs) with 95 % confidence intervals (95 % CI) were
pooled to assess the risk of Alzheimer's disease in elderly men with low
testosterone level. Seven prospective cohort studies with a total of 5251 elderly
men and 240 cases of Alzheimer's disease were included into the meta-analysis.
There was moderate degree of heterogeneity among those included studies (I
(2) = 47.2 %). Meta-analysis using random effect model showed that low plasma
testosterone level was significantly associated with an increased risk of
Alzheimer's disease in elderly men (random RR = 1.48, 95 % CI 1.12-1.96,
P = 0.006). Sensitivity analysis by omitting one study by turns showed that there
was no obvious change in the pooled risk estimates, and all pooled RRs were
statistically significant. This meta-analysis supports that low plasma
testosterone level is significantly associated with increased risk of Alzheimer's
disease in the elderly men. Low testosterone level is a risk factor of worse
cognitive function in the elderly men.


PMID: 26154489

 

-------------

[6] BMC Med. 2013 Apr 18;11:108. doi: 10.1186/1741-7015-11-108.

Testosterone therapy and cardiovascular events among men: a systematic review and
meta-analysis of placebo-controlled randomized trials.

Xu L(1), Freeman G, Cowling BJ, Schooling CM.

Author information:
(1)School of Public Health, Li Ka Shing Faculty of Medicine, The University of
Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong, China.

Comment in
Evid Based Med. 2014 Feb;19(1):32-3.

BACKGROUND: Testosterone therapy is increasingly promoted. No randomized
placebo-controlled trial has been implemented to assess the effect of
testosterone therapy on cardiovascular events, although very high levels of
androgens are thought to promote cardiovascular disease.
METHODS: A systematic review and meta-analysis was conducted of
placebo-controlled randomized trials of testosterone therapy among men lasting
12+ weeks reporting cardiovascular-related events. We searched PubMed through the
end of 2012 using "("testosterone" or "androgen") and trial and ("random*")" with
the selection limited to studies of men in English, supplemented by a
bibliographic search of the World Health Organization trial registry. Two
reviewers independently searched, selected and assessed study quality with
differences resolved by consensus. Two statisticians independently abstracted and
analyzed data, using random or fixed effects models, as appropriate, with inverse
variance weighting.

RESULTS: Of 1,882 studies identified 27 trials were eligible including 2,994,
mainly older, men who experienced 180 cardiovascular-related events. Testosterone
therapy increased the risk of a cardiovascular-related event (odds ratio (OR)
1.54, 95% confidence interval (CI) 1.09 to 2.18). The effect of testosterone
therapy varied with source of funding (P-value for interaction 0.03), but not
with baseline testosterone level (P-value for interaction 0.70). In trials not
funded by the pharmaceutical industry the risk of a cardiovascular-related event
on testosterone therapy was greater (OR 2.06, 95% CI 1.34 to 3.17) than in
pharmaceutical industry funded trials (OR 0.89, 95% CI 0.50 to 1.60).

CONCLUSIONS: The effects of testosterone on cardiovascular-related events varied
with source of funding. Nevertheless, overall and particularly in trials not
funded by the pharmaceutical industry, exogenous testosterone increased the risk
of cardiovascular-related events, with corresponding implications for the use of
testosterone therapy.

PMID: 23597181

Share this post


Link to post
Share on other sites

Dean, good analysis and I'd agree. This same phenomenon seems to exist for many biomarkers including insulin, thyroid hormones, and as you've said IGF-1 and T, and others. You're focus on why these are lowered rather than just analyzing the lowering itself is important in assessing the physiological impact and health, and this is often difficult when parsing epidemiological data.

Share this post


Link to post
Share on other sites
Men's testosterone bioavailable go down lots with aging.

 

 

Bioavailable Testosterone Linearly Declines Over A Wide Age Spectrum in Men and Women From The Baltimore Longitudinal Study of Aging.

Fabbri E, An Y, Gonzalez-Freire M, Zoli M, Maggio M, Studenski SA, Egan JM, Chia CW, Ferrucci L.

J Gerontol A Biol Sci Med Sci. 2016 Feb 27. pii: glw021. [Epub ahead of print]

PMID: 26921861


 

Abstract

 

BACKGROUND:

 

Age-related changes in testosterone levels in older persons and especially in women have not been fully explored. The objective of this study was to describe age-related trajectories of total testosterone (TT), ammonium sulfate precipitation-measured bioavailable testosterone (mBT), and sex hormone-binding glycoprotein (SHBG) in men and women from the Baltimore Longitudinal Study of Aging, with special focus on the oldest adults.

 

METHODS:

 

Participants included 788 White men and women aged 30-96 years with excellent representation of old and oldest old, who reported not taking medications known to interfere with testosterone. Longitudinal data were included when available. TT, mBT, and SHBG were assayed. Age-related trajectories of mBT were compared with those obtained using calculated bioavailable testosterone (cBT). Generalized least square models were performed to describe age-related trajectories of TT, mBT, and SHBG in men and women.

 

RESULTS:

 

mBT linearly declines over the life span and even at older ages in both sexes. In men, TT remains quite stable until the age of 70 years and then declines at older ages, whereas in women TT progressively declines in premenopausal years and slightly increases at older ages. Differences in age-related trajectories between total and bioavailable testosterone are only partially explained by age changes in SHBG, whose levels increases at accelerated rates in old persons. Noteworthy, although mBT and cBT highly correlated with one another, mBT is a much stronger correlate of chronological age than cBT.

 

CONCLUSION:

 

In both men and women, mBT linearly declines over the life span and even at old ages. Its relationship with age-related phenotypes should be further investigated.

 

KEYWORDS:

 

Aging; Men; Testosterone; Trajectories; Women

Share this post


Link to post
Share on other sites

I just ran across a study which appears to indicate that vitamin K (MK-4, to be precise) boost testosterone by 50%. At least in rodents.

Summary: https://suppversity.blogspot.com/2011/10/1g-of-vitamin-k2-mk-4-could-boost-your.html
Study: https://lipidworld.biomedcentral.com/articles/10.1186/1476-511X-10-158


Eat your natto (which has tons of MK-7) and if you want extra testerone, perhaps supplement with a bioidentical MK-4 supplement (synthetic, so OK for vegans).

Edited by Ron Put

Share this post


Link to post
Share on other sites

Thanks Ron.

Btw, Natto provides MK-7 primarily,  with small amounts of MK-5,6 and 8 and  little or no MK-4 (but the body may convert other forms of vitamin K to MK-4--see discussion at Masterjohn link).

 

Concepts and Controversies in Evaluating Vitamin K Status in Population-Based Studies (2016)

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4728622/

Quote

Phylloquinone [vitamin K1]  is plant-based, and concentrated in green leafy vegetables and certain plant oils (1). Longer chain menaquinones [vitamin K2] (menaquinone-7–menaquinone-13) have a bacterial origin, and are primarily concentrated in animal meats and fermented foods. Menaquinone-4, which is the most similar structurally to phylloquinone, is unique among the menaquinones in that it is not produced by bacteria, but instead is either formed from phylloquinone or a pro-vitamin menadione form used in animal feed. In the human diet, menaquinone-4 is concentrated in animal meats and dairy products. .

 

Determination of phylloquinone and menaquinones in food. Effect of food matrix on circulating vitamin K concentrations. (2000)
 
Vitamin K Content of Foods and Dietary Vitamin K Intake in Japanese Young Women (2007)
 

Menaquinone Content of Cheese (2018)

Cees Vermeer,  et al.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5946231/

 

Quantitative measurement of vitamin K2 in various fermented dairy products using a reliable high-performance liquid chromatography method (2013)

https://www.journalofdairyscience.org/article/S0022-0302(13)00034-9/fulltext

 

Multiple Vitamin K Forms Exist in Dairy Foods (2017)

https://academic.oup.com/cdn/article/1/6/e000638/4558638?searchresult=1

 

Chris Masterjohn:  The Ultimate Vitamin K2 Resource

 

Comparison of menaquinone-4 and menaquinone-7 bioavailability in healthy women  (2012)

https://nutritionj.biomedcentral.com/articles/10.1186/1475-2891-11-93

 
Vitamin K2 (Mccoy thread)

https://www.crsociety.org/topic/11990-vitamin-k2/

Edited by Sibiriak

Share this post


Link to post
Share on other sites

Is it wise to increase testosterone?  It's an anabolic hormone, possibly speeding up the aging process.

Share this post


Link to post
Share on other sites

Thanks, Sibiriak. Yep, natto is MK-7, that's why I mentioned bioidentical MK-4 (which is synthetic in most supplements).

As to testosterone, no, I would not recommend getting shots if one is within the normal range. Particularly if one has prostate tumors.

But there is also a correlation of very low testosterone and mortality (there is a similar, but less pronounced correlation with very high testosterone):
 

Results: During an average 11.8-yr follow-up, 538 deaths occurred. Men whose total testosterone levels were in the lowest quartile (<241 ng/dl) were 40% [hazards ratio (HR) 1.40; 95% confidence interval (CI) 1.14–1.71] more likely to die than those with higher levels, independent of age, adiposity, and lifestyle. Additional adjustment for health status markers, lipids, lipoproteins, blood pressure, glycemia, adipocytokines, and estradiol levels had minimal effect on results. The low testosterone-mortality association was also independent of the metabolic syndrome, diabetes, and prevalent cardiovascular disease but was attenuated by adjustment for IL-6 and C-reactive protein. In cause-specific analyses, low testosterone predicted increased risk of cardiovascular (HR 1.38; 95% CI 1.02–1.85) and respiratory disease (HR 2.29; 95% CI 1.25–4.20) mortality but was not significantly related to cancer death (HR 1.34; 95% CI 0.89–2.00). Results were similar for bioavailable testosterone.

Conclusions: Testosterone insufficiency in older men is associated with increased risk of death over the following 20 yr, independent of multiple risk factors and several preexisting health conditions.

https://academic.oup.com/jcem/article/93/1/68/2598158

Share this post


Link to post
Share on other sites

"In this study, lower total testosterone levels were associated with central obesity and established CVD risk factors including insulin and insulin resistance, glycemia, lipid profile, and blood pressure as well as emerging risk factors such as leptin, adiponectin, IL-6, and CRP"

Which is basically the complete opposite of people who are on CR. We're probably not going to be dying from cardiovascular disease.

I think that testosterone accelerates aging in men and that perhaps in some people there is a 'net benefit' whereby it's protective against diseases that will kill them earlier than any effect less testosterone might have on the intrinsic rate of aging. If you're on CR and have very minimal risk of some of the main causes of death, a higher level of testosterone is probably not beneficial.

I still think it's hard to extrapolate these findings from the general population onto someone who is doing CR, it needs to be contextualized to some extent. It's a bit like Michael Rae's thoughts on the DHA accelerated aging hypothesis, where a higher intake of DHA may accelerate aging in animals (and humans) on CR.

But perhaps if you have a very high risk of cardiovascular disease and autoimmune disease like Lupus, then maybe DHA might save you from early death and it's a 'net benefit' for you.

 

Edited by Matt

Share this post


Link to post
Share on other sites

I agree completely.  And from the data that I've seen from fellow CR practitioners -- including myself -- low testosterone is one of the normal consequences of CR.

(Speaking personally:  I remember when, after reaching a higher level of CR, well over 10 years ago, how my normal male attraction to the opposite sex suffered a severe downturn.  That desire still exists, but remains much reduced.)

The bottom line:  What's true is the general population, my not be true for CR practitioners.

  --  Saul

  

Share this post


Link to post
Share on other sites
On 7/13/2019 at 1:33 AM, Matt said:

... But perhaps if you have a very high risk of cardiovascular disease and autoimmune disease like Lupus, then maybe DHA might save you from early death and it's a 'net benefit' for you.

 

I am aware of the castrati/Korean eunuchs studies, as well as of the many studies suggesting that testosterone supplementation is beneficial to longevity.

It seems to me that the results are all over the map and it's not as simple as that. I read recently a meta study which basically concluded that testosterone is to an extent responsible for the difference in average longevity  between men and women, but solely because it increases the propensity for risky behaviors in males (which includes lifestyle and diet habits).

The only relevant study on CR and testosterone levels (in rhesus monkeys) appears to suggest an actual increase in circulating testosterone after long-term 30% CR:

"

Animals were subjected to 30% CR (CR, n = 5) or were fed a standard control diet (CON, n = 5) starting during their peripubertal period. Circulating testosterone (T) levels were measured across a 24-h period after 7 yr of dietary treatment and were found to be similar in CR and CON males; however, maintenance of daily minimum T levels was significantly higher in the CR animals. Semen collection was performed on the same cohort of animals three times per male (CR, n = 4; CON, n = 4) after 8 yr of treatment, and samples were assessed by a variety of measures. Parameters, including semen quality and sperm cell viability and function, showed less variability in semen samples taken from CR males, but overall testicular function and sperm quality were comparable regardless of diet. There is mounting evidence that CR may promote health and longevity in a wide range of organisms, including nonhuman primates. Importantly, our data suggest that moderate CR has no obvious lasting detrimental effect on testicular function and sperm parameters in young adult primates and may in fact help maintain higher levels of circulating T."

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2957152/

Share this post


Link to post
Share on other sites
2 hours ago, Ron Put said:

The only relevant study on CR and testosterone levels (in rhesus monkeys) appears to suggest an actual increase in circulating testosterone after long-term 30% CR:


Of course the CR monkeys you are referring to (at the NIA) weren't really 30% CRed, and didn't live longer than controls (see here for discussion), so the fact that they didn't have lower T than controls doesn't really answer the question of whether serious CR lowers testosterone in humans (which it appears to in general, see [1]), or whether it is healthy or even necessary for longevity benefits of CR.

Human data trumps monkey data when available, especially when it comes from a few of us on this forum! 

--Dean 

----

1. Aging Cell. 2010 Apr;9(2):236-42. doi: 10.1111/j.1474-9726.2010.00553.x. Epub
2010 Jan 20.

Long-term effects of calorie restriction on serum sex-hormone concentrations in
men.

Cangemi R(1), Friedmann AJ, Holloszy JO, Fontana L.

Author information: 
(1)Center for Human Nutrition, Washington University School of Medicine, St.
Louis, MO, USA.

Calorie restriction (CR) slows aging and consistently reduces circulating sex
hormones in laboratory animals. However, nothing is known regarding the long-term
effects of CR with adequate nutrition on serum sex-hormone concentration in lean 
healthy humans. In this study, we measured body composition, and serum total
testosterone, total 17-beta-estradiol, sex hormone-binding globulin (SHBG), and
dehydroepiandrosterone sulfate (DHEA-S) concentrations in 24 men (mean age 51.5
+/- 13 years), who had been practicing CR with adequate nutrition for an average 
of 7.4 +/- 4.5 years, in 24 age- and body fat-matched endurance runners (EX), and
24 age-matched sedentary controls eating Western diets (WD). We found that both
the CR and EX volunteers had significantly lower body fat than the WD volunteers 
(total body fat, 8.7 +/- 4.2%; 10.5 +/- 4.4%; 23.2 +/- 6.1%, respectively; P =
0.0001). Serum total testosterone and the free androgen index were significantly 
lower, and SHBG was higher in the CR group than in the EX and WD groups (P < or =
0.001). Serum 17beta-estradiol and the estradiol:SHBG ratio were both
significantly lower in the CR and EX groups than in the WD group (P < or =
0.005). Serum DHEA-S concentrations were not different between the three groups. 
These findings demonstrate that, as in long-lived CR rodents, long-term severe CR
reduces serum total and free testosterone and increases SHBG concentrations in
humans, independently of adiposity. More studies are needed to understand the
role of this CR-mediated reduction in sex hormones in modulating the pathogenesis
of age-associated chronic diseases such as cancer and the aging process itself.

DOI: 10.1111/j.1474-9726.2010.00553.x 
PMCID: PMC3569090
PMID: 20096034  [Indexed for MEDLINE]

Share this post


Link to post
Share on other sites
7 hours ago, Dean Pomerleau said:

Of course the CR monkeys you are referring to (at the NIA) weren't really 30% CRed, and didn't live longer than controls (see here for discussion), so the fact that they didn't have lower T than controls doesn't really answer the question of whether serious CR lowers testosterone in humans (which it appears to in general, see [1]), or whether it is healthy or even necessary for longevity benefits of CR....

I do not make the claim that there is a clear answer. I am merely stating that the studies I've seen on testosterone levels are all over the map. There is clear evidence that testosterone declines as humans age, markedly so after 70 or so. There is clear evidence that very low levels of testosterone correlate with higher mortality, as do abnormally high levels. Notably, testosterone levels in Okinawan elderly men, who as a population effectively practiced CR, were higher than those measured among mainland Japanese subjects.

I looked at the study you posted and it is far from clear the low testosterone levels found among the 24 CR subjects are by themselves beneficial to longevity. It's entirely possible that their otherwise extremely healthy diet and lifestyle have a protective effect, despite the low levels of testosterone. We also don't have a T baseline for the CR subjects, making any conclusions based on this study questionable. The primate studies are at least considerably better controlled.

Edited by Ron Put

Share this post


Link to post
Share on other sites

Hi Ron!

I would take the study on humans as much more seriously than the one on monkeys -- which, as Dean pointed out, is badly flawed.

You must remember, that seriously CRed people are not identical to the general population.  One of the signatures of the onset of even moderate CR is a drop in testosterone; in males, this leads to a serious drop in sexual desire.

This has been observed, not only in the participants in Luigi's study, but among the many CR practitioners who contributed to the old CR Society mailing lists -- some of this material may still be available in the CR Society archives.   

Share this post


Link to post
Share on other sites
10 hours ago, Ron Put said:

I looked at the study you posted and it is far from clear the low testosterone levels found among the 24 CR subjects are by themselves beneficial to longevity. 

Nobody is claiming that it is. Just that low testosterone in middle aged men practicing CR is the rule, rather than the exception, regardless of what monkey CR data says. Whether it is beneficial, harmful or neutral in the context of a healthy CR lifestyle has long been a matter of debate around here. Reread the opening post of this thread for discussion of the nuances surrounding CR and testosterone. 

--Dean 

Share this post


Link to post
Share on other sites
Quote

Dean Pomerleau:  Obesity, and especially metabolic syndrome, are associated with increased mortality risk, and reduced T and FT levels. It may therefore be that low T (& FT) is a marker for impaired androgen signalling in men with metabolic syndrome...

 
 
Cf. Testosterone and All-Cause Mortality in Older Men: The Role of Metabolic Syndrome (2018)
PMID: 29577108
 
Quote
4. Conclusion

Low total and bioavailable testosterone are associated with increased all-cause mortality in elderly men with MetS. Among them, this increase in mortality risk is also observed for men suffering for testosterone deficiency as compared with those with normal or high physiological levels of hormone. By contrast, testosterone was not associated with mortality among men without MetS [...]

 

Share this post


Link to post
Share on other sites
9 minutes ago, Sibiriak said:

By contrast, testosterone was not associated with mortality among men without MetS [...]

Metabolic Syndrome is about the opposite of the state of possibly all CRONnies; I'd guess that the only way CRON and MetS could arise together would be from a genetic defect.

  --  Saul

Share this post


Link to post
Share on other sites
3 hours ago, Saul said:

Metabolic Syndrome is about the opposite of the state of possibly all CRONnies; I'd guess that the only way CRON and MetS could arise together would be from a genetic defect.

  --  Saul

Actually, it appears well established that very low testosterone correlates with higher mortality. It is also associated with the accumulation of adipose tissue.

The study Dean cited doesn't have a baseline, compares a small number of CR subjects with subjects with unknown dietary and lifestyle habits, and as far as testosterone levels, contradicts the observation that elderly Okinawans, who effectively practiced moderate CR, combined with very low protein, very low fat predominantly plant-based diet, had higher levels of testosterone than their counterparts on the mainland, who consumed about 20% more calories.

The rhesus study I posted above is certainly better controlled and its results are in line with other research I've seen.

Again, my first reaction would be to argue that the very healthy lifestyle and diet of the CR subjects may negate immediate adverse manifestations of low testosterone (and come to think of it, what is "low" in this case?)

See this:
"On the other hand, circulating levels of sex hormones control fat mass distribution and expansion, mainly through activation of estrogen and androgen receptors in adipose tissue. Of interest, a recent work highlighted the profound impact of testosterone on cardiovascular function improving functional capacity, heart rate, muscle strength, and glucose metabolism in elderly patients with coronary heart failure [85]. We hypothesize that the cardiovascular effects of testosterone may be also mediated by adipose tissue, which embeds the heart and the most important vessels (coronaries, carotids, aorta, etc.) and is an active site of conversion of androgens into estrogens, through aromatase activity.

In conclusion, adequate levels and balance of circulating sex hormones are necessary to maintain a correct distribution and size of adipose tissue, which in turn is fundamental to keep a normal reproductive and sexual function. For this reason, screening of obese patients for hypogonadism is deemed necessary in order to better understand the pathophysiology of coexistent metabolic alteration, in order to target it with a replacement therapy. The delicate issue of whether testosterone decline, observed with aging, causes adipose tissue accumulation, or whether weight gain primarily disrupts testicular steroidogenesis, is still unclear and needs further studies."
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3253446/

There is no strong evidence that low testosterone levels correlate with good health or longevity. On the contrary, very low testosterone levels correlate with all sorts of issues, including CVD and osteoporosis.

Share this post


Link to post
Share on other sites
Quote

Ron Put: ...  testosterone levels in Okinawan elderly men, who as a population effectively practiced CR, were higher than those measured among mainland Japanese subjects.

I'm curious how big the difference was.   When you have a moment,  could you cite the study that has those testosterone numbers.

(I'm aware that Wilcox et al.  reported that "older Okinawans appear to have higher DHEA levels than older Americans.https://www.researchgate.net/publication/51442644_The_Okinawan_Diet_Health_Implications_of_a_Low-Calorie_Nutrient-Dense_Antioxidant-Rich_Dietary_Pattern_Low_in_Glycemic_Load)

Edited by Sibiriak

Share this post


Link to post
Share on other sites

Thanks!

So it was a comparison with U.S. men, not mainland Japanese men.   Apparently  US men's testosterone levels have been declining markedly over the past few decades.    I had mine tested in 2017 and 2018 and I was surprised that my T  and FT   were relatively high for my age (882 ng/dL, 14.4  nmol/L), which might be a little concerning.      (I'm not doing real CR;  I maintain a BMI  around 21-21.5.)

 

Edited by Sibiriak

Share this post


Link to post
Share on other sites
7 hours ago, Sibiriak said:

Thanks!

So it was a comparison with U.S. men, not mainland Japanese men....

 

Actually, I remembered reading it in the context of Japanese men and just did another quick search, which shows the following testosterone levels for the the average Japanese male:

Age 60-69: 12 mmol/L, which is 346 ng/dL

Age 70-79: 11.5 mmol/L, which is 332 ng/dL.

https://onlinelibrary.wiley.com/doi/full/10.1111/j.1442-2042.2005.01143.x

So, while the Japanese as a group appear to retain slightly higher testosterone levels than Americans as they age, the Okinawans, at 439 ng/dL at the age of 70, still retained significantly higher testosterone levels than the average Japanese male.

The Okinawans also consumed about 80% of the calories consumed by the average Japanese on the mainland (effectively practicing CR) and their diet was significantly more heavily plant-based, with lower ratios of protein and fat.

Edited by Ron Put

Share this post


Link to post
Share on other sites

Okinawan's start off almost half the level of DHEA and Testosterone (if I remember correctly) than Americans but it declines much more slowly. Eventually, Okinawan's end up with higher testosterone levels at older ages.

Last time I had my testosterone checked it was 412 ng/dl about 2.5 years ago (I'm 35 in Oct). So I guess that's pretty low for my age...

Some Okianwan's might be doing CR, some not. Many of us here are doing CR intentionally and are a lot more strict about it than Okinawan's.

As for the Rhesus monkeys, the results were inconsistent in many ways with what is observed in mice, rats, and humans. There were no differences in fasting glucose for some of the groups in the NIA study (especially for females) or it took until they were over 20+ years old for them to diverge. In humans, both males and females have significantly lower insulin and glucose (as we see in mice). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3832985/  CR females having *higher* triglycerides than the control group (total opposite of what we see in humans).

I could go on and on but this has been covered so many times. I highly recommend you check out Michael's post on it over at SENS.

There's actually some data in mice or rats (wish I could find it..) where they show that castrated males live longer than intact males. Males who were given estrogen have significantly longer lifespans, even longer than female mice and females that were given estrogen. Females that were given testosterone lived the shortest.  

Low testosterone (in ad lib, poor diet, population) correlates with CVD. But we are not them...  I'm sure you've seen the results of Fontana's studies on people of the CRS, we are not getting CVD. We are not getting Diabetes. And we aren't having issues with too much fat (for sure).

We actually have some good data on individuals here. We're not just stats or hypotheticals, we're real people, doing real CR, showing real results that are contrary to the data you're presenting and we have low testosterone. 

From the study Dean cited:

"Interestingly, out of the 81 eunuchs, three were centenarians, aged 100, 101, and 109 years. The current incidence of centenarians is one per 3,500 in Japan and per 4,400 in the United States. Thus, the incidence of centenarians among Korean eunuchs is at least 130 times higher than that of present-day developed countries."

https://www.sciencedirect.com/science/article/pii/S0960982212007129

Edited by Matt

Share this post


Link to post
Share on other sites

Fig. 6. Trajectories of decline in DHEA levels (ng/mL) with age in Okinawans and Americans  [Wilcox, linked above]

 

image.png.a4b4e2ab2dfbd0d7db14ca3f8fb0dd3b.png

 

 

 

Edited by Sibiriak

Share this post


Link to post
Share on other sites

Create an account or sign in to comment

You need to be a member in order to leave a comment

Create an account

Sign up for a new account in our community. It's easy!

Register a new account

Sign in

Already have an account? Sign in here.

Sign In Now

×