Ask Dr Rand McClain

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Hi Marco, I have not seen suppression of thyroid production with the use of L-carnitine. I have seen L-carnitine used to increase time to exhaustion in both novice and well-conditioned athletes. The MOA appears to be the preferential use of fat over glycogen for use as energy. If you are using thyroid replacement, you are overriding the need for endogenous production so supplements that are purported to affect your production should not be a concern. If you notice an increased need for thyroid replacement when using the supplement(s) (L-carnitine), I would simply increase the thyroid dose. Ie, you have already "crossed the line" of replacement therapy, so even if the supplement affected your endogenous thyroid, practically speaking, it does not affect anything except the strength of the pill you are already taking.

BPC-157 shows much promise in the repair of tendons. The rat studies are impressive and BPC-157's use in the humans that I know is equally impressive. I know bodybuilders and strength athletes ("Strongmen") who have used it successfully through daily dosing (usually 250 mcg either directly into the tendon or in a triangular pattern that straddles the tendon). I do not see as much success with TB500 for MSK injuries, but, as you note, these peptides are not within the scope of a US physician's practice, so my observations are just that and by chance rather than intent (mine anyway).

First and foremost, when it comes to TRT, the question is whether you have symptoms and signs of low T. The numbers (lab assays) are secondary (we treat people, not numbers). Libido, energy, sense of well-being are all personality driven in large part, so often times, ironically, those with the lowest T levels or who have had them the longest are the last to come seeking help because their personality has kept them going. And, patients often mistakenly compare themselves to others rather than a younger version of themselves when self-evaluating whether they have an issue. The "dead giveaway" more often than not is body composition changes. Personality (at least directly) does not drive one's body composition, and I typically see an athlete who knows how to and is doing all the right things but is struggling with body composition. That's when the low-T gets their attention. I understand the desire not to "throw in the towel", but I ask you to reconsider the way you look at it. If you would be served by testosterone replacement, why wouldn't you use it the same way you would use other means of helping yourself to feel, look and be better? Sure, it is one more thing you would be "dependent" upon, but no worse than having to train, eat, sleep, brush your teeth, shower, use the restroom, shave (maybe), etc.. Certainly, one thing we know for sure is that the situation is not going to get any better with time/age. In my experience, using a SERM may actually lead to some increase in endogenous production of T, but, assuming you do not have SE's from the SERM, the resultant T increase is inconsequential to quality of life. Ie, one doesn't feel or get an effect from the increase in T. It is fair for me to comment that certainly use of a SERM is "un-natural" and could be considered "throwing in the towel", so why not go straight to supplementation with something more effective (why fly from LA to SF via NY when you can take a straight shot from LA to SF?) (also, it's "natural" to get sick and die one day so I think we might agree that "natural" isn't necessarily all that it is cracked up to be). If you are intent on giving it a try however, then consider clomiphen citrate and/or hcg to get the endogenous production up and to see how you feel. If Clomid gives you unwanted SE's you could try anastrozole instead.
 
Defy Medical TRT clinic doctor
Hi Vince, please help me with your question a bit: you have low SHBG and want to raise it? Your concern being that you have a free estrogen level that is too high (presumable with a free T level that is a high percentage of total T)? My initial response would be to simply reduce your estrogen more with the use of an aromatase inhibitor to accomplish preserving high free T percentage and get to your goal of lowering your estrogen to your target.
 
Hi "HanginOn",
I found this on the DFH website: http://catalog.designsforhealth.com/Magnesium-Chelate. It is just a bit stronger than what you have, but still 25%.
It's tricky wading through the supplement world because of all the claims (the one's supported by studies) made that we read and say, "sure, I want that effect", etc. I make supplement recommendations based upon goals. Eg, you mention curcumin. Great supplement if you have too much inflammation or are concerned about pancreatic cancer (is in your family history or you used to be a big drinker or smoker, eg). But if your concern were protection against bacterial infection, you would not (except in rare circumstances) take an antibiotic as prophylaxis. The Chinese categorize supplements (herbs) as Superior for the ones that are just good for you, sort of, no matter what, and sort of like vitamin B's, eg. Then they have another category for treating illness when it arises. The same holds true in our paradigm. A good multivitamin would contain vitamins that we always need in ample supply and that can't hurt (note that one can almost always overdose something good for oneself - even water). But, let's say you eat plenty of oily fish or cruciferous vegetables, then you wouldn't necessarily want to supplement with omega-3 sources or DIM, respectively. And, if you are at risk for colon cancer because it runs in your family and/or you have UC or Crohns or just a poor diet, then taking a daily ASA 81mg is probably prudent to help protect you. Make sense?
 
Hi Marco, I have not seen suppression of thyroid production with the use of L-carnitine. I have seen L-carnitine used to increase time to exhaustion in both novice and well-conditioned athletes. The MOA appears to be the preferential use of fat over glycogen for use as energy. If you are using thyroid replacement, you are overriding the need for endogenous production so supplements that are purported to affect your production should not be a concern. If you notice an increased need for thyroid replacement when using the supplement(s) (L-carnitine), I would simply increase the thyroid dose. Ie, you have already "crossed the line" of replacement therapy, so even if the supplement affected your endogenous thyroid, practically speaking, it does not affect anything except the strength of the pill you are already taking.

BPC-157 shows much promise in the repair of tendons. The rat studies are impressive and BPC-157's use in the humans that I know is equally impressive. I know bodybuilders and strength athletes ("Strongmen") who have used it successfully through daily dosing (usually 250 mcg either directly into the tendon or in a triangular pattern that straddles the tendon). I do not see as much success with TB500 for MSK injuries, but, as you note, these peptides are not within the scope of a US physician's practice, so my observations are just that and by chance rather than intent (mine anyway).

First and foremost, when it comes to TRT, the question is whether you have symptoms and signs of low T. The numbers (lab assays) are secondary (we treat people, not numbers). Libido, energy, sense of well-being are all personality driven in large part, so often times, ironically, those with the lowest T levels or who have had them the longest are the last to come seeking help because their personality has kept them going. And, patients often mistakenly compare themselves to others rather than a younger version of themselves when self-evaluating whether they have an issue. The "dead giveaway" more often than not is body composition changes. Personality (at least directly) does not drive one's body composition, and I typically see an athlete who knows how to and is doing all the right things but is struggling with body composition. That's when the low-T gets their attention. I understand the desire not to "throw in the towel", but I ask you to reconsider the way you look at it. If you would be served by testosterone replacement, why wouldn't you use it the same way you would use other means of helping yourself to feel, look and be better? Sure, it is one more thing you would be "dependent" upon, but no worse than having to train, eat, sleep, brush your teeth, shower, use the restroom, shave (maybe), etc.. Certainly, one thing we know for sure is that the situation is not going to get any better with time/age. In my experience, using a SERM may actually lead to some increase in endogenous production of T, but, assuming you do not have SE's from the SERM, the resultant T increase is inconsequential to quality of life. Ie, one doesn't feel or get an effect from the increase in T. It is fair for me to comment that certainly use of a SERM is "un-natural" and could be considered "throwing in the towel", so why not go straight to supplementation with something more effective (why fly from LA to SF via NY when you can take a straight shot from LA to SF?) (also, it's "natural" to get sick and die one day so I think we might agree that "natural" isn't necessarily all that it is cracked up to be). If you are intent on giving it a try however, then consider clomiphen citrate and/or hcg to get the endogenous production up and to see how you feel. If Clomid gives you unwanted SE's you could try anastrozole instead.

Many thanks for the in-depth replies to my concerns and putting things in a common sense perspective.

According to the authors of a clinical trial https://clinicaltrials.gov/ct2/show/NCT01769157 , L-carnitine and thyroid hormone tended to antagonize reciprocally in human body. This is obviously a conundrum for anyone who is hypothyroid but that has benefited from taking L-carnitine. By the way, here are the papers regarding thyroid hormone suppression of L-carnitine:
https://www.ncbi.nlm.nih.gov/pubmed/15591013
https://www.ncbi.nlm.nih.gov/pubmed/11201848

Given the above, do you still think the reported suppressive effects can be "overridden" by thyroid replacement dosage adjustment?

One other issue of concern regarding L-carnitine is some recent data which shows that in the gut it transforms to TMAO which has some cardiac toxicity: https://www.ncbi.nlm.nih.gov/pubmed/25636076

Thyroid optimization is a big focus of mine right now (long time struggling with this). I recently tried adding some T4 to my 1 grain natural desiccated thyroid and I felt worse and my rT3 increased. I cannot seem to get my ferritin levels up no matter how much iron I take, for one, as I know how important that is for thyroid function. I feel I have been and still am chronically under-dosed, but it's a catch-22 at this point when increasing thyroid replacement with either NDT or T4 may backfire if there are other possible imbalances making replacement work against me (on a side note, I have already tried both T3 and T4 monotherapy as well as T3 added to NDT). In addition, I have a genetic methylation defect (MTHFR C677T +/+) and am taking various supplements to support proper methylation, however, it would be great to get some insight with respect to supplement navigation. Even guys like me that have a lot of knowledge still need a coach.

As far as consideration of TRT, one huge hold-back is that I suffered from an "idiopathic" DVT that presented out of nowhere back in 2012 and have been on anticoagulant prophylaxis (Xarelto 10mg qd) since 2014. I am at a standstill of what to do or not to do next, as I have not been able to determine the cause of the thrombophilia in the first place (had every test under the sun to date and we cannot determine whether it's familial, acquired, or a combination). I am not even sure if I should remain on an anticoagulant and most hematologists aren't of any help since they really only treat existing pathologies (all are also oncologists). I am looking into getting with a research facility with a major university for a more extensive workup and evaluation to determine the etiology, but even then, I may reach a dead end. While it may not change my direction whether to use TRT or not, at least knowing the cause would put things in perspective. I don't know if Clomid would make any difference with respect to this.

Would you consider your practice and treatment approach to be in the realm of functional medicine?

Again would appreciate your thoughts.
 
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ratbag

Member
I had an iron absorption problem as well. It turned out taking Vitamin C solved my problem. It took me 2 years to figure that out. Now I don't have to take iron supps any longer, only vit C and my ferritin is fine now.
 
Hi Vince, please help me with your question a bit: you have low SHBG and want to raise it? Your concern being that you have a free estrogen level that is too high (presumable with a free T level that is a high percentage of total T)? My initial response would be to simply reduce your estrogen more with the use of an aromatase inhibitor to accomplish preserving high free T percentage and get to your goal of lowering your estrogen to your target.

Dr let me rephrase, for a low SHBG guy would it be (more) worthwhile to monitor Free Estrogens given that low SHBG = high Free T and thus = high Free Estrogen? Perhaps in the low SHBG guy we need to look at lower LC/MS/MS numbers as well from the typical 21-30 that is suggested.
 
I had an iron absorption problem as well. It turned out taking Vitamin C solved my problem. It took me 2 years to figure that out. Now I don't have to take iron supps any longer, only vit C and my ferritin is fine now.

I already take 3-4g of vitamin C with different forms of iron and STILL have low ferritin. I also checked for internal bleeding and was cleared. Something else is blocking absorption or my iron needs are higher than average, the mystery continues.
 

ERO

Member
Hello Dr. McClain:

As somewhat of a follow-on to the question that Vince posed, have you ever seen a case of actual TRT success in guys with low SHBG? I am talking SHBG in the teens. That is where my SHBG is and TRT to me feels like I am injecting water or in the case of topical T, using a generic hand lotion. When I say "success" I don't mean nice numbers on blood work - I mean things like a decent libido, maybe some ability to gain a little muscle and lose a bit of fat and some additional energy.

Thank you,
 

ta406

Member
Hi Dr. McClain,

I have a question regarding cortisol. I have had a saliva test that shows that my cortisol levels are high. Especially at night which I believe causes me to wake up in the early a.m. hours and its next to impossible to fall back asleep. I am 5' 9", 210lbs, 13% body fat My diet is clean and weight train 4x a week.

I am on trt. I get frequent blood work and try to maintain my testosterone and estrogen levels at healthy levels. I donate blood every few months, both because my RBC slowly increases and because my dad needed a few blood transfusions to keep him alive after an
illness so I understand how important donating is. I have had my thyroid checked and my doc said everything looked good. I have tried, meditation, mindfulness and more natural supplements and combinations of supplements than I can count. Nothing really seams to work. I was recently reading that low doses of Propranolol may help to combat this. Do you think this is something worth exploring or would you happen to have any other suggestions? Thanks
 
Dr McClain,my question is, if a person came into your practice complaining of all the Low T symptoms, and you have Blood tests ran that came back good on the T levels, what would be your first suspicion of what else might be wrong that you would check for? I am sure you have seen this before. Thanks for your help.
 

1Draw

Member
Dr. McClain:

Many thanks for taking time to answer questions on this forum. Very rare for a MD of your expertise to do this freely and openly. Very unselfish on your part! Also thanks to Nelson for putting this together for all of us members with some very good questions that we can't find answers for.

My questions is I'm a high SHBG guy and have been on T therapy now for almost 3 years. Started out with pellets and have tried most every therapy there is. I'm still looking for the "sweet spot" that is so elusive. I'm currently on .25 ml TCyp with grapeseed oil IM every 3.5 days and no HCG.

My hematocrit always jumps up and am having to donate every 8 weeks to keep in line. On my last blood test, my E2 was 60 and was put on exemestane .25 mg 2 x week since I have problems with anastrozole. I'm due for a new blood test in couple weeks and a consult with Defy also. I am very sensitive to AI's in general and would prefer not to take them if at all possible.

My question is would a high SHBG guy do well with daily T injections to keep hematocrit and E2 in line? I understand that I would probably have to live with low free T if I do this but to eliminate the need for 7 donations a year and E2 in line without an AI would be priceless for me! Also, what daily dosage would you recommend for someone on 100 mg a week?

Many thanks for your reply.
 
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1Draw

Member
1Draw, how does your ferritin hold up giving that much blood? I've never heard of anyone donating that frequently before.

My bad Ratbag.... Just corrected the post. I donate every 8 weeks not 4. Looking back at all my blood test, I've never had ferritin tested. Thanks for pointing this out.
 

OMI100

Member
Dr. McClain:
1. Like all the other members here I want to give a BIG "Thank You" for your time and energy in answering our questions.
2. I have looked at some of the questions and answers on the Clomid VS HCG issue here, but none quite like my question. Question is based on a long term TRT protocol with TD T cream with the addition of HCG and possible addition of CLOMID. So here goes:
2.a Fertility is NOT an issue as this question is from an older guy who does not have to worry about that :)
2.b Are the actions / pathways of HCG and CLOMID the same?
2.c If one takes BOTH (HCG and CLOMID) is there a canceling out of results and is it contraindicated?
2.d Are there situations where LOW dose CLOMID (say 12.5mg once or twice per week along with HCG and TRT)would be beneficial?

Thanks....
 
Hi Vince,
With regard to chasing the elusive magic estradiol (E2) NUMBER, it can be difficult to hit because typically as one reduces E2, the SHBG is reduced which of course frees up more E2, which lowers SHBG, etc. This explains why many see a drop from say 55pg/ml to 28pg/ml of E2 with just one dose of strategically placed anastrozole 1mg, and yet require anastrozole 1mg every other day to get E2 to 15-20pg/ml. As for the determining the magic E2 state that works for each individual, I find that (generally) men tend to do well with E2 (sensitive assay is what I find adequate) between 15-20pg/ml, but exceptions exist such as with strength athletes. Some "Strongmen" competitors I know complain of tendon/joint pain and strength reduction when E2 is maintained that low and prefer levels closer to 30-35pg/ml. Also, men who are sensitive to E2 tend to do better with slightly higher levels (but I have seen the reverse as well). Eg, if E2 drops below 15mg/ml, these men tend to complain of lack of genital sensitivity which can lead to ED and lack of libido. In such case, we agree to shoot for a slightly higher E2 range to protect against its ever dipping too low.
As for your specific question of measuring FREE E2, I have no experience using this assay. Your assertion that it may be a better assay to use is a good one though since it gives us even more detailed information. I will consider using it if I run across a particularly difficult E2 titration case and report back.
 
Hi 1Draw,
A few ways that I know of to reduce SHBG are to lower your E2 (I prefer to use the "sensitive" assay) to a tipping point that I see around just over 20pg/ml. In addition, maintenance of a high (or at least adequate) protein diet, supplementing with nettle, and/or supplementing with a relatively small dose of an anabolic steroid tends to reduce SHBG. The relatively small anabolic steroid dose would be, eg, oxandrolone 5mg - a dose that typically would not, by itself, infer any anabolic benefit to an adult male.
Red blood cell increases, along with hemoglobin and hematocrit increases, are most often a result of sleep apnea. This condition frequently goes undiagnosed until patients begin using testosterone, at which time the elevations become apparent because the LEVERAGE of testosterone applied to the nightly oxygen debt results in these assay elevations. I call it "training in your sleep". But, before you get any ideas about skipping your cardio workouts, this kind of nightly hypoxic training is not beneficial to your health. Sleep apnea is associated with pulmonary hypertension, daytime fatigue, and getting fat (not only affecting your food choices, but the metabolism of them). Perhaps as or more important is that if you are training in your sleep you are certainly not getting the rest and recuperation, regeneration and rejuvenation you need. (And, no, even if you slept all day, the hypoxic "training" you get at night is not the same as climbing hills on your bike for 7-8 hours).
Rarely, individuals have what is known as a JAK2 gene mutation which drives the production of RBC's, hemoglobin and hematocrit upward.
In either case, therapeutic phlebotomies are useful to keep blood from getting too viscous and avoiding SE's therefrom. However, if sleep apnea is the cause of the assay elevations, in my opinion, much more important is to fix the underlying cause so that one can get the requisite rest and all that comes with it nightly. I have seen so many guys who come to my office with their water and food, exercising well, and taking all the right supplements but complain they cannot get to their fitness goals. I ask them how much sleep they are getting and I hear, "well, I'm working 2 jobs right now, so I'm getting about 5-6 hours every night". No way to grow muscle, lose fat, and achieve optimum health this way. If you are bagging 9-10 hours of rack time, BUT, you aren't getting enough oxygen during this time, you are not getting requisite rest required to achieve optimum health and fitness as described above. One with sleep apnea is actually better off spending say 4 hours (one typical first sleep cycle) "asleep" and then the next 4 hours in a position in which he or she can at least breath well enough to get sufficient oxygen perfusion, possibly "awake" but still resting. Better option for sleep apnea of course is to see an ENT specialist who has experience treating sleep apnea and address treatment and resolution of the sleep apnea.
For those with the JAK2 gene mutation, the only treatments of which I am aware use "cancer" drugs (eg, hydroxyurea), but I have had some success with a combination of therapeutic phlebotomies while limiting consumption of iron in attempts to deplete iron store to the point at which hemoglobin can no longer be made in excess (no iron, no hemoglobin - sort of a self-induced iron deficiency "anemia" state).
Re exemestane v anastrozole, I find a loose correlation between 1mg of anastrozole with 25mg of exemestane. The MOA's are different, but exemestane can be used effectively to reduce conversion from T to E.
And, yes, by dosing your T more frequently (and keeping your T titer more narrow), often you can avoid as much conversion from T to E and thereby reduce the need for an anti-estrogen therapy.
 
Hi Orrin,
Clomid and HCG work by very different MOA's. Clomid is a selective estrogen receptor blocker (so, eg, it blocks estrogen reception at the pituitary, but not at the liver) while HCG mimics the effect of LH on the Leydig Cells (testosterone producing) of the testes. The net result one is typically trying to achieve is to get the testicles producing more testosterone (and in cases of infertility, thereby get the local production of testosterone in sufficient amount to catalyze the production of sperm by the adjacent Sartoli cells).
Whether one has high T or high E, the pituitary will not produce LH to stimulate the Leydig Cells to make more T (part of what is referred to as "negative feedback"). What if I have low T and high E? Why wouldn't my body what to produce more T? Because, estrogen is made from testosterone, so, again, if (either T or) estrogen is high, then even if T is low, again because E is made from T, then the pituitary will not send a signal (LH) to produce more T. I know, a gyp, but it is the way it works - don't shoot the messenger.
So, with Clomid, by blocking the pituitary's reception of E, when T is low, it satisfies the conditions under which the pituitary can send a signal to make more T. With HCG, we are imply overriding the system and telling the testicles directly to make more T. So, you can see that both HCG and Clomid could be used together to effectuate a rise in T.
Not sure that a weekly dose (as well as such a small one - Clomid dose it typically 50mg either every day or every other day) of Clomid would be effective at stimulating T production.
 

charile12

Member
Hi doc. I am on trt for sencondary hypogonadism. tried clomid, raised my lh to about 7 but only raised T to 500. Still have some low t symptoms. I started injections from endo. Gave me 200 mg bi-weekly. But I am injecting 100 1x per week. (same dosage - just more frequent) I am not concerned about fertility so I have not asked for hcg - at this point am glad he offered injections.
My question - should i be taking hcg even though i dont care about fertility? I am just thinking that LH may have other roles in the body. Also, if my Thyroid Ft3 and ft4 are on the low normal range, would that cause a low -t?
Thank you for your time Dr
 
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