One of the more mysterious conditions afflicting low-carb Paleo dieters has been high serum cholesterol. Two of our most popular posts were about this problem: Low Carb Paleo, and LDL is Soaring – Help! (Mar 2, 2011) enumerated some cases and asked readers to suggest answers; Answer Day: What Causes High LDL on Low-Carb Paleo? (Mar 4, 2011) suggested one possible remedy.
On the first post, one of the causes suggested by readers was hypothyroidism – an astute answer. Raj Ganpath wrote:
Weight loss (and VLC diet) resulting in hypothyroidism resulting in elevated cholesterol due to less pronounced LDL receptors?
Kratos said “Hypothyroidism from low carbs.” Mike Gruber said:
I’m the guy with the 585 TC. It went down (to 378 8 months or so ago, time to check again) when I started supplementing with iodine. My TSH has also been trending up the last few years, even before Paleo. So hypothyroidism is my primary suspect.
Those answers caused me to put the connection between hypothyroidism and LDL levels on my research “to do” list.
Chris Masterjohn’s Work on Thyroid Hormone and LDL Receptors
Chris Masterjohn has done a number of blog posts about the role of LDL receptors in cardiovascular disease. His talk at the Ancestral Health Symposium was on this topic, and a recent blog post, “The Central Role of Thyroid Hormone in Governing LDL Receptor Activity and the Risk of Heart Disease,” provides an overview.
His key observation is that thyroid hormone stimulates expression of the LDL receptor (1). T3 thyroid hormone binds to thyroid hormone receptors on the nuclear membrane, the pair (a “dimer”) is then imported into the nucleus where it acts as a transcription factor causing, among other effects, LDL receptors to be generated on the cell membrane.
So higher T3 = more LDL receptors = more LDL particles pulled into cells and stripped of their fatty cargo. So high T3 tends to reduce serum LDL cholesterol levels, but give cells more energy-providing fats. Low T3, conversely, would tend to raise serum cholesterol but deprive cells of energy.
Other Pieces of the Puzzle
Two other facts we’ve recently blogged about help us interpret this result:
- LDL particles are not only lipid transporters; they also have immune functions. See Blood Lipids and Infectious Disease, Part I, Jun 21, 2011; Blood Lipids and Infectious Disease, Part II, Jul 12, 2011.
- T3 becomes low when glucose or protein are scarce. Thyroid levels alter to encourage resource utilization when resources are abundant and to conserve resources when they are scarce. See Carbohydrates and the Thyroid, Aug 24, 2011.
We can now assemble a hypothesis linking low carb diets to high LDL. If one eats a glucose and/or protein restricted diet, T3 levels will fall to conserve glucose or protein. When T3 levels fall, LDL receptor expression is reduced. This prevents LDL from serving its fat transport function, but keeps the LDL particles in the blood where their immune function operates.
If LDL particles were being taken up from the blood via LDL receptors, they would have to be replaced – a resource-expensive operation – or immunity would suffer. Apparently evolution favors immunity, and gives up the lipid-transport functions of LDL in order to maintain immune functions during periods of food scarcity.
High LDL on Low Carb: Good health, bad diet?
Suppose LDL receptors are so thoroughly suppressed by low T3 that the lipid transport function of LDL is abolished. What happens to LDL particles in the blood?
Immunity becomes their only function. They hang around in the blood until they meet up with (bacterial) toxins. This contact causes the LDL lipoprotein to be oxidized, after which the particle attaches to macrophage scavenger receptors and is cleared by immune cells.
So, if T3 hormone levels are very low and there is an infection, LDL particles will get oxidized and cleared by immune cells, and LDL levels will stay low. But if there is no infection and no toxins to oxidize LDL, and the diet creates no oxidative stress (ie low levels of omega-6 fats and fructose), then LDL particles may stay in the blood for long periods of time.
If LDL particles continue to be generated, which happens in part when eating fatty food, then LDL levels might increase.
So we might take high LDL on Paleo as a possible sign of two things:
- A chronic state of glucose deficiency, leading to very low T3 levels and suppressed clearance of LDL particles by lipid transport pathways.
- Absence of infections or oxidative stress which would clear LDL particles by immune pathways.
The solution? Eat more carbs, and address any remaining cause of hypothyroidism, such as iodine or selenium deficiency. T3 levels should then rise and LDL levels return to normal.
Alternatively, there is evidence that some infections may induce euthyroid sick syndrome, a state of low T3 and high rT3, directly. And these infections may not oxidize LDL, thus they may not lead to loss of LDL particles by immune pathways. So such infections could be another cause of high LDL on Paleo.
Gregory Barton’s Experience
Gregory Barton is an Australian, 52 years old, living in Thailand, where he keeps goats, makes goat cheese and manages a large garden which can be seen on http://www.asiagoat.com/.
Gregory left a comment with an intriguing story, and I invited him to elaborate in a post. Here’s Gregory’s story. – Paul
Gregory’s Writing Begins Here
One of the claims of low carb dieting is that it will normalize the symptoms of metabolic syndrome. Blood pressure, blood sugar and blood lipids, it is claimed, will all come down on a low carb diet, in addition to weight. For most people this happens. But there is a significant minority of people on Paleo and other low carb diets whose blood lipids defy this claim. (See the list of low-carb celebrities with high LDL in this post.)
Why should this happen? Why should some people’s lipids fall on low carb while other people’s lipids rise? Suboptimal thyroid might be the proximate cause for lipids rising on a low carb or paleo diet. Broda Barnes and Lawrence Galton have this to say about thyroid disorders:
“Of all the problems that can affect physical or mental health, none is more common than thyroid gland disturbance. None is more readily and inexpensively corrected. And none is more often untreated, and even unsuspected.” — Hypothyroidism: The Unsuspected Illness
I went very low carb in April in an effort to address metabolic issues, eating as little as 15grams carbohydrate per day. I had great results with blood pressure, sleeping, blood sugar and weight loss. But lipids bucked the trend.
I had expected triglycerides and cholesterol to drop when I cut the carbs, but they did the opposite: They surged. By July my total cholesterol was 350, LDL 280, and triglycerides bobbed around between 150 and 220.
I did some research and found several competing theories for this kind of surge:
- Saturated fat: The increase in saturated fat created a superabundance of cholesterol which the liver cannot handle. Also, Loren Cordain has claimed that saturated fat downregulates LDL receptors.
- Temporary hyperlipidemia: The surge in lipids is the temporary consequence of the body purging visceral fat. Jenny Ruhl has argued that within a period of months the situation should settle down and lipids should normalize.
- Hibernation: The metabolism has gone into “hibernation” with the result that the thyroid hormone T4 is being converted into rT3, an isomer of the T3 molecule, which prevents the clearance of LDL.
- Malnutrition: In March, Paul wrote that malnutrition in general and copper deficiency in particular “… is, I believe, the single most likely cause of elevated LDL on low-carb Paleo diets.”
- Genetics: Dr. Davis has argued that some combinations of ApoE alleles may make a person “unable to deal with fats and dietary cholesterol.”
I could accept that saturated fat would raise my cholesterol to some degree. However, I doubted that an increase in saturated fat, or purging of visceral fat, would be responsible for a 75% increase in TC from 200 to 350.
There are two basic factors controlling cholesterol levels: creation and clearance. If the surge was not entirely attributable to saturated fat, perhaps the better explanation was that the cholesterol was not being cleared properly. I was drawn to the hibernation theory.
But what causes the body to go into hibernation? According to Chris Masterjohn, a low carb diet could be the cause. Although he does not mention rT3, he warns,
“One thing to look out for is that extended low-carbing can decrease thyroid function, which will cause a bad increase in LDL-C, and be bad in itself. So be careful not to go to extremes, or if you do, to monitor thyroid function carefully.”
If low carb is the cause, then higher carb should be the cure. Indeed, Val Taylor, the owner of the yahoo rT3 group, commented that “it is possible that the rT3 could just be from a low carb diet.” She says, “I keep carbs at no lower than 60g per day for this reason.”
Cortisol and Getting “Stuck” in Hibernation
So what about temporary hyperlipidemia? Bears hibernate for winter, creating rT3, but manage to awaken in spring. Why should humans on low carb diets not be able to awaken from their hibernation? There are many people who complain of high cholesterol years after starting low carb.
A hormonal factor associated with staying in hibernation is high cortisol. It has been claimed that excessively high or low cortisol, sustained over long periods, may cause one to get “stuck” in hibernation mode. One of the moderators from the yahoo rT3 group said:
High or low cortisol can cause rT3 problems, as can chronic illness. It would be nice if correcting these things was all that was necessary. But it seems that the body gets stuck in high rT3 mode.
James LaValle & Stacy Lundin in Cracking the Metabolic Code: 9 Keys to Optimal Health wrote:
When a person experiences prolonged stress, the adrenals manufacture a large amount of the stress hormone cortisol. Cortisol inhibits the conversion of T4 to T3 and favours the conversion of T4 to rT3. If stress is prolonged a condition called reverse T3 dominance occurs and lasts even after the stress passes and cortisol levels fall. (my emphasis)
What I Did
First, I got my thyroid hormone levels tested. A blood test revealed that I had T4 at the top of the range and T3 below range. Ideally I would have tested rT3, but in Thailand the test is not available. I consulted Val Taylor, the owner of the yahoo rT3 group, who said that low T3 can cause lipids to go as high as mine have and, “as you have plenty of T4 there is no other reason for low T3 other than rT3.”
I decided to make these changes:
- Increase net carbs to ~50 grams per day. Having achieved my goals with all other metabolic markers I increased carbs, taking care that one hour postprandial blood sugar did not exceed 130 mg/dl.
- Supplement with T3 thyroid hormone.
- In case the malnutrition explanation was a factor, I began supplementing copper and eating my wife’s delicious liver pate three times per week.
I decided to supplement T3 for the following reasons:
- The surge in TC was acute and very high. It was above the optimal range in O Primitivo’s mortality data.
- I increased carbs by 20-30g/day for about a month. TC stabilized, but did not drop.
- The rT3 theory is elegant and I was eager to test my claim that the bulk of the cholesterol was due to a problem with clearance rather than ‘superabundance’.
What happened?
I started taking cynomel, a T3 supplement, four weeks ago. After one week triglycerides dropped from 150 to 90. After two weeks TC dropped from 350 to 300 and after another week, to 220. Last week numbers were stable.
Based on Paul’s recent series on blood lipids, especially the post Blood Lipids and Infectious Disease, Part I (Jun 21, 2011), I think TC of 220 mg/dl is optimal. As far as serum cholesterol levels are concerned, the problem has been fixed.
I believe that thyroid hormone levels were the dominant factor in my high LDL. Saturated fat intake has remained constant throughout.
My current goal is to address the root causes of the rT3 dominance and wean myself off the T3 supplement. I hope to achieve this in the next few months. My working hypothesis is that the cause of my high rT3 / low T3 was some combination of very low carb dieting, elevated cortisol (perhaps aggravated by stress over my blood lipids!), or malnutrition.
Another possibility is toxins: Dr Davis claims that such chemicals as perchlorate residues from vegetable fertilizers and polyfluorooctanoic acid, the residue of non-stick cookware, may act as inhibitors of the 5′-deiodinase enzyme that converts T4 to T3. Finally, Val Taylor claims that blood sugar over 140 mg/dl causes rT3 dominance. I couldn’t find any studies confirming this claim, and don’t believe it is relevant to my case. Val recommends low carb for diabetics to prevent cholesterol and rT3 issues but warns not to go under 60g carb per day.
Issues with T3 Supplementation
There are some factors to consider before embarking upon T3 supplementation:
- Preparation: In order to tolerate T3 supplement you have to be sure that your iron level and your adrenals are strong enough. This requires quite a bit of testing. I’ve read of people who cut corners with unpleasant results.
- Practicalities: T3 supplementation requires daily temperature monitoring in order to assess your progress. People who are on the move throughout the day would find this difficult.
- Danger: Once you get on the T3 boat you can’t get off abruptly. Your T4 level will drop below range and you will be dependent on T3 until you wean yourself off. If you stopped abruptly you could develop a nasty reaction and even become comatose.
My advice for anyone doing very low carb
As Chris Masterjohn said, in the quote above, if you are going to do very low carb, check your thyroid levels. I would add: Increase the carbs if you find your free T3 falling to the bottom of the range. It might be a good idea to test also for cortisol. A 24-hour saliva test will give you an idea whether your cortisol levels are likely to contribute to an rT3 issue. It might also be a good idea to avoid very low carb if you are suffering from stress – such as lipid anxiety!
Gregory Barton’s Conclusion
I also think my experience may help prove thyroid hormone replacement to be an alternative, and superior, therapy to statins for very high cholesterol. Statins, in the words of Chris Masterjohn,
“… do nothing to ramp up the level of cholesterol-made goodies to promote strength, proper digestion, virility and fertility. It is the vocation of thyroid hormone, by contrast, to do both.”
Paul’s Conclusion
Thanks, Gregory, for a great story and well-researched ideas. The rapid restoration of normal cholesterol levels with T3 supplementation would seem to prove that low T3 caused the high LDL levels.
However, I would be very reluctant to recommend T3 supplementation as a treatment for high LDL on Paleo. If the cause of low T3 is eating too few carbs, then supplementing T3 will greatly increase the rate of glucose utilization and aggravate the glucose deficiency.
The proper solution, I think, is simply to eat more carbs, to provide other thyroid-supporting nutrients like selenium and iodine, and allow the body to adjust its T3 levels naturally. The adjustment might be quite rapid.
In Gregory’s case, his increased carb consumption of ~50 g/day was still near our minimum, and he may have been well below the carb+protein minimum of 150 g/day (since few people naturally eat more than about 75 g protein). So I think he might have given additional carbs a try before proceeding to the T3.
Gregory had a few questions for me:
GB: What if one is glucose intolerant and can’t tolerate more than 60 grams per day without hyperglycemia or weight gain?
PJ: I think almost everyone, even diabetics, can find a way to tolerate 60 g/day dietary carbs without hyperglycemia or weight gain, and should.
GB: What if raising carbs doesn’t normalize blood lipids and one finds oneself ‘stuck in rT3 mode’?
PJ: I’m not yet convinced there is such a thing as “stuck in rT3 mode” apart from being “stuck in a diet that provides too few carbs” or “stuck in a chronic infection.” If one finds one’s self stuck while eating a balanced diet, I would look for infectious causes and address those.
Finally, if I may sound like Seth Roberts for a moment, I believe this story shows the value of a new form of science: personal experimentation, exploration of ideas on blogs, and the sharing of experiences online. It takes medical researchers years – often decades – to track down the causes of simple phenomena, such as high LDL on low carb. We’re on pace to figure out the essentials in a year.
via this link:
Magnificent post. I can’t believe I didn’t think of that once. I knew each individual fact but hadn’t put them all together. Looks like one more link for the “why is my cholesterol through the roof on low carb?” collection.
Paul this was a nice clinically oriented blog about thyroid hormone and clearly lays out what an endocrinology book should say about a high lipid count, especially the LDL fraction. Cholesterol gets converted to pregnenolone using T3 and vitamin A as co factor in making steroids in response to hypothalamic signals. I think it is well known by most clinicians that supplementing T3 lowers lipids. It is also well known that cortisol (CRH) directly inhibits TSH. I wrote about these things three months ago on June 8th. http://jackkruse.com/hormones-robb-wolf-john-cannell-adrenal-fatigue-leptin-weight-loss-health-growth-hormone/ The sad part is few clinicians use this options an instead jump to statins first which are generally worthless in this clinical scenario. Dr. Kruse
I’m curious about your attributing this phenomenon to “low-carb Paleo.” A low-carb diet isn’t necessarily paleo. So are you implying that low-carbers who aren’t doing paleo are somehow protected from this?
Hi Jack,
Thanks for the further info. The pathways are so complex I think clinicians ignore them and just want “proven” therapies.
Hi Beth,
Yes … the “Paleo” part is just historical, my first post on this referred to “Low-Carb Paleo” and so I’ve continued that … you’re right, it’s the low-carb only that matters, and any very low-carb diet could be problematic.
Sorry to not have yet read your book… but plan to! However I have one simple question, when you refer to grams of carbs do you mean total grams or the Atkins “net grams?”
Good question Mike. I would exclude fiber, as Atkins did. We actually exclude most vegetable carbs too, as some glucose is lost in digestion.
What if the lowering of T3 is an adaptation and in part responsible for the longevity effect postulated for low carb diets?
Hi Emily,
It is an adaptation, and yes lower T3 is associated with greater longevity. Mario made that point: http://perfecthealthdiet.com/?p=4383#comment-28288.
But if you look at the 3 studies Mario cited, the difference in T3 levels is tiny. Centenarians have a statistically significant, but very slight, decrease in T3.
When you look at protein restriction studies, mild protein restriction extends lifespan but severe protein restriction greatly shortens it. (Note: Protein restriction reduces T3 just like carb restriction.)
I think a similar pattern will hold with carbs. If you just make the body a little low in glucose, so it has to conserve resources, lifespan will be extended. If you create a major glucose deficiency, with big alterations in T3 and rT3, lifespan will be shortened.
This is all speculative of course …
Best, Paul
Thanks, Paul. Since I am hypothyroid, a lot of your recent posts have been very germane to me. I get migraines and find that eating low carb (50-100g usually)helps. I am going to see if I can bump it up a little (say, up to at least 100g), and see if I remain migraine free.
What I have found is that since starting a paleo diet 6 months ago, my medication (T3 supplementation) has decreased from 50 mcg per day to 36.25 mcg per day. I go for another test soon, so I may need to be adjusted again, but this level feels right, for now. I credit it to the reduction in inflammation and being much better nourished. As well, my IBS symptoms have decreased since I discovered and eliminated FODMAPs foods. Hopefully this will heal up my gut and the thyroid production associated with it.
Any suggestions for avoiding migraines when upping carbs? Some of the research I found suggested it was the glucose spike of high GI foods that caused the migraine. Might it make sense to eat lower GI carbs or only high GI ones with lots of protein and fat?
Thanks,
Karin
Hi Karin,
I think it’s the presence of ketones that helps most with migraines. So what I would do is intermittent fasting: 16 hours a day with no food except MCT oil, then all your eating in an 8 hour window with 100 g carb.
Having some hours of ketosis each day should reduce glutamate levels in the brain and enable mitochondrial repair and neuronal healing … then the carbs will prevent the glucose deficiency issues.
I do intermittent fasting anyways, except I have tea with cream instead of coconut oil. I don’t think there is much in the cream other than fat, and from what I have heard, it doesn’t “kick you out” of the fast. Would you concur?
Carbs today were 120g, and no migraine yet, so that is a good indication!
My migraines seemed to be tied with my cycle. Or when its cycle time I tend to crave certain foods which I eat and they cause the migraines. Or I can be strict for months on end with no sign of migraine but when I slack off migraines return.
Paul, this was a great post.
I always appreciate your posts, Paul. I was glad to see that there is more of a distinction between VLC and LC, terms that seem to be interchangable in the blogosphere. For most people who aren’t thinking paleo, even 125 gms of carbs is VLC, so it seems like a good practive to define ranges rather than use acronyms.
In any event, the amount of carbs suggested in the post for purposes of maintaining optimal health reminded me of Lutz’s recommendation to target 75gms of carbs per day, in his excellent book, ‘Life without Bread’. Peter at Hyperlipid has also suggested that a minimum of 75gms of carbs is a good target.
What about the use of tocotrienols to lower cholesterol? There have been studies that show it works.
Perhaps Ray Peat has been correct all along. On philosophical grounds I have been shunning lab tests, as much of the current “conventional” theories of chronic disease seemed bunk to me. That being said, what sort of physical signs/symptoms would be present to even prompt lab testing? Also, my next request would be a synopsis about possible infections as “conventional” medicine often discounts infectious causes. Lastly, C. Masterjohn mentions both thyroid and cholesterol receptivity on LDL receptors. Would not increased dietary cholesterol upregulate LDL receptor activity? There are many foods that are rich in cholesterol and fat as opposed to little cholesterol and fat. This was a great post, keep up the good work.
I think the possibility of diet triggering hibernation in humans is a fascinating topic. I always felt this was a possibility – something our bodies could be hardwired to do – and always felt it was triggered by either very low carb, high protein and/or fat. On occasion, I suspected I experienced this phenomenon but thought it might be too far fetched. After reading this post, I would love to know more.
I really enjoyed this post, Paul. Some of the cholesterol info can get pretty dense and I appreciate your ability to describe it so it’s more enjoyable and easier to understand.
Gregory,
Thanks for sharing your perspective and personal experience – well done! Love the chart tracking your history with the dramatic changes in such a short amount of time. I’m interested to hear your continued experience after you’ve removed the T3 supplement.
Thanks,
Mark
Emily when some one has a lower T3 for adaptation they wont have any of the signs of co morbid LR. I have seen tons of VLC with low T3 and when you look at their Reverse T3 and cortisols they are thru the roof. That means the thyroid is shut off by the hypothalamus and no amount of T3 or T4 will fix it. You fix the LR problem and the Thyroid improves. So many have plateaus because of this its not funny. It frustrates me that endocrinologists tell PCPs all the time you just need to look at the TSH and T3 and T4. If CRH or Rev T 3 is up your thyroid panel is worthless because the brain turned it all off.
Hi JKC,
Cream won’t end the fast, but you might find MCTs/coconut oil more helpful for the migraine, as they are more ketogenic.
Hi Gabriel,
Unfortunately, medicine has been working on a model of acute disease, and they only know how to discover infections and chronic disease when they become extremely severe. The research model has to change to develop better tests that catch problems, especially infections, earlier. Until then, we have to read tea leaves a lot.
Great post, Paul. I came across an article you might find interesting (Effect of Cholesterol on Mortality and Quality of Life up to a 46-Year Follow-Up): http://www.sciencedirect.com/science/article/pii/S0002914911016006
Hi Scott,
Thanks, it is interesting, and a bit puzzling. Perhaps there is a mechanism via calorie restriction? Interesting data point.
Great article, thanks,
I prefer this to copper deficiency 🙂
That’s what I thought too, although I haven’t checked those boards. Not enough gycoproteins led to reverse T3 and then LDL going up, the latter from 6.5 to 13.7. Still have to get some tests done to see if in my case there is a change. I know, I’m threatening that I do them for a while.
Interesting about reducing your synthetic T3. I’ll keep that in mind.
About Scott’s article, yes, puzzling to say the least. I don’t see any clear reference to calorie restriction in the summary.
Oh, I forgot, the idea of ‘stuck in high reverse T3’ mode might mean that some people, because of high cortisol or adrenalin due to stress or other causes don’t revert to normal immediately even if conditions have improved – more calories, more carbs. I’m thinking also of an exaggerated response to losing fat as in lowered leptin as a way to defend the fat mass. Some people’s leptin goes lower than others, is highly variable, for the same amount of fat loss. That would influence thyroid hormone too.
Paul,
Concerning alchohol and Diflucan… did or do you consume perhaps a small glass of wine every now and then while taking it? I have been instructed to avoid it at all costs but I was wondering if a 1-2 glasses of wine perhaps every other week or so would hurt. I am not a heavy drinker by any means… beacause I am so weary of it’s health effects I only ever do it if I am very pressured into it. But I do enjoy the flavor of a glass of the red stuff occassionally.. and the social aspect. I take a regular NAC and limit PUFAS and fructose, so in general I’m pretty good to my liver and enzymes test well.
Also, I was wondering if you could tell me more about the Chinease medicine… I am very interested and would love to know more about it so I may find a practitioner in my area to combine with my daily dosage of Diflucan over the next 3 months (got prescribed it for 1 month but get more every 4 weeks after liver enzymes are tested).
I apologize for the multitude of spelling errors in my comments by the way!
Hi Bill,
I continued to have a glass of wine occasionally, but maybe I shouldn’t have. I have stopped the fluconazole.
I think the Chinese medicine worked well, not great but well. It seemed to be less toxic than fluconazole and similarly effective. However, it’s more expensive and labor intensive, and doesn’t taste good.
The key thing is to have a trustworthy Chinese pharmacy that you can get the medicines from. We have one in Boston’s Chinatown, but not sure what others would do.
Do you consider you fungal infection gone, or still more to go?
A very interesting account. Thanks Paul and Gregory. As for adjusting T3 level in days, here is a study that lends support to that http://www.ncbi.nlm.nih.gov/pubmed/812882 (Which I found here http://tiredthyroid.com/rt3.html). Malnourished men in Calcutta halved their rT3 in days following feeding treatment.
Paul,
in your conclusion, you’re saying that adding carbs would make the body adjust rapidly, you don’t think T3 supplementation is a good idea. Maybe not. In my case, 3 months of extra carbs didn’t seem to work, I just put weight on and my hormonal problems that I considered as consequences of low thyroid hormone (luteal phase defect) didn’t get better. That’s why I asked for T3 supplementation. Maybe I should have waited more, but I was convinced it would make a difference with the LDL and at the time I didn’t know that it was a sign of glucose deficiency, I thought either conversion problem or from weight loss.
Hi Bill,
Still more to go, I’d say I’m 80% there, but I’m taking a break from medicines for a bit.
Hi Kate,
Very nice paper, thanks for the link!
Hi simona,
Yes, I don’t want to discourage thyroid hormone supplementation in hypothyroidism … just in glucose deficiency (or protein deficiency), when it would defeat the adaptive response to the deficiency.
Thanks Paul! Hoping to finally beat this infection for good by the time I graduate in the Spring of 2012. It would be nice to not have to deal with seb derm anymore! I always said I wanted to have “perfect health” by the time I graduated… meaning no skin issues, no sleep issuses and no digestive issues! I am not sure how bad my infection is… but I imagine I have had it for at least 2-3 years. Hopefully 8 months will be enough!
Also, did you monitor your liver enzymes while on Diflucan? I am afraid my doc will freak at the slightest change and take me off… I have read that it is mostly harmless but unforetunately I have little experience to argue with him about it…
What should the conversion of T4 to T3 be: is it 1 to 1? My Free T4 is 1.24( range.89- 1.76) and Free T3 is 2.6( range 2.3 to 4.2). Doc thinks all is ok with this and TSH of 1.7.
I am trying to understand if the Free T3 is where it should be, or a little low in relation to the T4. Also, cannot genetics and toxic metals inhibit the conversion process?
Thanks, very interesting.
Hi steve,
We can’t infer anything wrong from numbers in the normal range, unless you have symptoms of problems. There’s no specific ratio between T4 and T3 that is optimal; it depends on circumstances and diet.
If you lack hypothyroid symptoms or low metabolism, then I would just try to optimize diet and health on general principles and let the thyroid hormones go where they want.
Hi Gregory,
Thanks for the info about protein/carb consumption.
The difference between intracellular T3/T4 and extracellular is also interesting, I will keep that in mind when thinking about those diseases.
By all means, send us updates on your progress! A lot of people are interested.
Pascal, thanks. I mentioned your comment in the Saturday post to give it more visibility.
Tom, for “increased carbs” check out the Excel figure. It shows when he increased carbs and to what amount.
Best, Paul
Paul is correct in assuming that I didn’t consume 150g protein/carb. I would readily confess to being impetuous in my decision to experiment with Cynomel. Ideally, as a good scientist, I would have waited six months from the time of starting very low carb. I regret not experimenting further with carb increases.
In my defense I would mention that, rational or irrational, I was in the grip of lipid anxiety. The unrelenting surge in lipids from week to week was highly unnerving. Although I believe that the danger of cholesterol is overrated, I don’t think one can dismiss LDL levels entirely. (Why should every other blood component have an optimal range but not LDL, as the sceptics claim?)And if very high LDL is dangerous, or, if not dangerous in itself, indicative of a dangerous imbalance, how long does it take for one’s health to suffer? How long could I have safely waited: one month, six months, a year? I don’t think there is an answer to this question. I was therefore reluctant to wait another three months before starting T3.
Getting stuck in rT3 mode
The question of getting stuck in rT3 mode is, I agree, contentious. I put it to Val. She sent me a link to an interesting article which claims that:
“Reduced thyroid transport into the cell is seen with a wide range of common conditions, including insulin resistance, diabetes, depression, bipolar disorder, hyperlipidemia (high cholesterol and triglycerides), chronic fatigue syndrome, fibromyalgia, neurodegenerative diseases (Alzheimer’s, Parkinson’s and multiple sclerosis), migraines, stress, anxiety, chronic dieting and aging.”
and
“The intracellular T3 deficiency seen with these conditions often results in a vicious cycle of worsening symptoms that usually goes untreated because standard thyroid tests look normal.”
http://nahypothyroidism.org/thyroid-hormone-transport/#reverseT3
This “vicious cycle” might account for some people ‘getting stuck’ in rT3 mode, especially if they suffered from more than one factors mentioned above, such as insulin resistance and hyperlipidemia.. On the other hand, Paul’s claim that my carbs were still too low in the month during which I raised carbs might be correct. In the absence of tests we can but speculate.
Steve, take a look at the article that I cited above. It claims that blood levels of T3 and T4 are not a reliable indicator of levels in the cell.
MarkES, in a few months, after, finishing the T3 course and weaning off, I’ll post a postscript. Wish me luck.
Paul,
You might want to mention that high cortisol levels can be normalized by the intake of high doses of Vitamin C. Therefore in addition to increasing carb intake, supplementation with higher doses of Vitamin C may also help.
http://www.ncbi.nlm.nih.gov/pubmed/11862365
http://www.ncbi.nlm.nih.gov/pubmed/11590482
A wonderful article. I may have missed it but could you please expand on “increased carbs”. What were they specifically?
what you recommend for recovering from hypothalamic amenorrhea? what dietar wise do i need to focus on? anything supplement wise i should be more adament about? i have seen fish oil causes period to stop in some women too, any thoughts? if PUFA efa/dha are the only required fats EFAs i dont get how PUFAs are shunned? can you explain?
Hi Mallory,
I would recommend our general diet. They key I think is avoiding PUFA and fructose.
Not sure I understand the question about EPA/DHA/PUFA. You want a low level of PUFA in your body, but a balance between subtypes. Most people are way too high in omega-6 and low in omega-3. So the best strategy is to minimize omega-6, and get some dietary omega-3, but food amounts, not supplement amounts.
Paul What a wonderful series of posts!! I treat thyroid problems in my practice and have Hashimoto’s myself. I check FT3/RT3 ratios on almost everyone. I think this is the best lab test for your thyroid related metabolic state. The most useful is the old fashioned history and physical exam. Old time thyroid docs did this with no lab tests to guide them. The thyroid gland controls the metabolism of the hypothalamis and pituitary. TSH allows the hypothalamis/pituitary to receive adequate thyroid hormone in the face of a hypometabolic state (starvation etc). Chronic elevated systemic inflamation and malnutrition inhibit thyroid function and thus ALL endocrine function, including adrenals. The longer I am on the PHD and appropriate supplements, the less desicatted thyroid I require. It used to take 21/2 tabs daily and now I use 1/2 tab daily. I have increased my safe carb intake as weight loss is no longer my main goal and feel great! Thanks Paul
Hi William,
Thank you for sharing! I’m intrigued that you find rT3:T3 valuable in all patients. It’s great to hear clinical experience.
And of course I’m very happy your hypothyroidism is improving. In many cases it may be easier to work the cure than to figure out the cause!
Paul, you might remember my cholesterol was consistently above 500 on PHD with around 100-150gr carbs and really none of the hypotheses around (choline, fatty liver, thyroid, vascular damage) seemed relevant so far. Thyroid was prime suspect, but my TSH was significantly lower with the high cholesterol numbers than on my earlier diet with the normal (in your sense) cholesterol values, and therefore I discounted that. So I thought perhaps my genes cause me to downregulate LDL receptors with high (/high saturated) fat diet. But low T3 might indeed be behind this as this rat study abstract also might suggest (I have no T3 tests from the 6 months of very high cholesterol period unfortunately):
“Serum 3,5,3′-triiodothyronine (T3) is increased by overnutrition and decreased by starvation. The production rate of T3 was increased by overfeeding (82%)… Feeding a weight maintenance diet with high CHO mimiced serum T3 and rT3 changes of overfeeding, substitution of CHO by FAT those of starvation.” PMID: 348487
After I increased safe carbs significantly, cholesterol gradually decreased. I seem to have got back so far in a few months to around 300. But with my low protein diet and moderately active lifestyle 600 carb calories does not do it for me. I seem to need approx double that, which seems to leave only around 30-35% of calories as fat. Do I have Kitavan ancestors?
Hi donat,
Interesting. A few other people, including Danny Roddy, have reported needing significantly higher carbs than is usual. I don’t know why. Athletic activity would be one reason. Can you describe your “moderately active lifestyle” for me? And how “low protein” are you?
It would be interesting to see your T3/rT3 numbers if you get those tested.
55 gram protein/day. Hara hachi bu. (My Okinawan ancestry this time.) 1 Sisson style lift heavy things and 1 tabata sesson and about 20km barefoot slow-speed run per week. I tend to try to avoid sitting during the day. Stand-squat-kneel-sit routine at the keyboard. I will get a free T3 soon, sadly nobody can do rT3 in this corner of the world.
donat’s experience is interesting … curious if cholesterol reduction is more related to either increase in carbs, or decrease in saturated fat; or perhaps a combination of both.
Thanks,
Mark
MarkES: difficult to know with any certainty, but my impression was that reducing saturated fats was relevant but not enough here.
Started high fat PHD around the end of last year. (Constant supply of liver, mushrooms, zinc, selenium, iodine both before, during and after the high fat/ high TC period.) TC (both LDL and HDL, with variation in TG) kept consistently climbing. By Mid-March TC was around 500: previous months fat/day 205gr, SaFa/day 101gr. Around April/May I started the TC maneuver (in honor of Travis Culp of course): no butter or coconut oil, tallow restricted. In June TC now slightly under 500, previous month fats: 163gr and 52gr. Right direction but far from good enough. Had to keep trying harder. End of last month: TC significantly under 300, previous month fats: 80 and 18. (Calories a bit higher on high fat, protein constant throughout.)
Hi donat,
I wonder if 20 km running plus standing-squatting during the day amounts to significant glucose utilization. Let’s say you run 3 hours a week and use 300 glucose calories/hr, so 900 calories; and standing-squatting uses 100 glucose calories/hr at 4 hours per day, or 400 extra glucose calories. Then our 100 g would become 200 g/day with standing/squatting plus an extra 225 g/wk with running …
Given your low protein intake an otherwise moderate glucose shortfall might have a significant impact on thyroid hormone and LDL.
Paul, many thanks very helpful as always. Your last sentence must be the key: consistently low protein will presumably enhance the effect of even a mild glucose shortfall.
But could a deficiency forcing me to double my carbs really come from squatting-standing? My understanding was that low intensity activity uses minimal carbs, so even if I’m on my feet 6-8 hours shouldn’t most of the energy come from fats? My high intensity exercise cannot be much more than 30-45 mins/week. Also on high 70-80% fat I was doing roughly the same without any apparent problems, without even a single episode of hitting the wall in running etc.
So assuming I create a small deficiency with a big effect like you say, –why do I need to apparently double rather than just slightly increase my carbs?
Could the following make any sense at all? I have various health issues but digestion is not one of them. Cron-o-meter tells me roughly 350 carbs and 50 fiber for the recent cholesterol-lowering period. However if I add straight starches like potato and rice and sugar from fruit and veg that’s more like 200gr or maybe a little more but not too much more.
Could it be that for me, and perhaps more generally for people with an appropriate gut flora, your assumption about leafy vegetable carbs being turned to fat could be generalized to the non-sugar part of root veg and even fruit? If tenable, this would mean that as you say I was only mildly glucose deficient and I am now actually not absorbing more carbs than necessary for sorting that.
Hi donat,
Glucose utilization during activity varies significantly among people. Obese people tend to be obligate glucose utilizers even on mild activity; healthy, athletically trained people tend to utilize nearly all fat. Glucose utilization standing or squatting could vary anywhere from 0% to 50%, but most likely would be 10-20%.
I think you need to experiment to find what works for you. I don’t think it’s unreasonable to expect to need 1,000 carb+protein calories per day with your activity levels.