Monthly Archives: January 2015

Hepcidin, Weight Loss, Thyroid, Ferritin and Iron

Hepcidin, Weight Loss, Thyroid, Ferritin and Iron

References: Nemeth Annual Review of Nutrition, Ahmed WJG, Paoletti

Are you trying to lose weight and can’t? Think it might be your thyroid?   You feel tired all the time.   Your doctor doesn’t measure your ferritin or your iron.   Is there a link and connection you should know about? Yes!

Hepcidin is the link. Ever heard of it? It was discovered in about 2000. It is a peptide hormone that is used to regulate iron. It’s output is increased in inflammatory states.   When you are overweight, you start out behind the eight ball because fat cells spew out inflammatory markers 24/7.   Serum iron falls due to iron trapping in macrophages and decreased gut absorption.   The protein ferroportin is present in gut cells and it is turned off by hepcidin.

If you have severe enough inflammation, you can even become anemic because your body will simply reject any iron.   It’s hard to measure hepcidin, but a C-reactive protein is a pretty good surrogate marker.   Your ferritin is lower in your blood because you just don’t have any iron absorbtion.   And what is ferritin? It’s your storage form of iron that in inside cells and in blood.   It reflects your total body iron. But it’s function is more basic, it converts the Fe+2 ferrous ion into the F3+3 form which protects your body from the dangerous “Fenton” reaction that creates hydroxyl ions.

How does all this fit together? Pretty elegantly.   Iron deficiency promotes fat storage. And the effect of that on your thyroid is slightly indirect, but perverse.   Low ferritin and your thyroid doesn’t function like it should. There are some 80 proteins inside the cell that need iron in part of their structure to process the gene signaling that T3 starts.   When you have low ferritin, your iron is low, and your gene signaling will be disrupted.

Ironically, if there is severe inflammation, ferritin can be elevated as an “acute phase reactant”, but that would be a red herring in this case. Most of the time, folks with normal TSH and T4 but with all the symptoms of hypothyroidism like being cold, weight gain, lousy hair will have a low ferritin and a modestly high CRP (as a stand-in for the unmeasurable hepcidin.)

Does that sound too confusing?   Read Byron Richards summary. He adds some insight into inflammatory diets and yeast overgrowth setting off inflammation. That’s another topic for another day.

WWW. What will work for me.   If you want to lose weight, your first step might be to get off of carbs and have lower nutrition for the yeast in your gut. Then, get your ferritin, iron and CRP checked.   The picture will emerge that you really did need a bit more thyroid.   It may not be any more complicated than that.   And if your doctor won’t allow it, you can always just but the test at “AnyLabTestNow”.


Pop Quiz

  1. Hepcidin is your iron controlling hormone. T or F

That’s it

  1. It regulates the amount of iron your absorb, store, tuck away or activate? T or F

If this is all you learned, I’m happy.

  1. In response to inflammation, hepcidin goes up, and iron goes down? T or

True. Now you are on a roll

  1. When iron (ferritin) goes down, your thyroid can’t work right. T or F

Bingo. Ready for the bonus round?

  1. So, once you are overweight, your first step should be to turn off inflammation, which tones down hepcidin, which allows iron to rise, which allows your thyroid to work.   T or F

Whew. Now you have got it perfectly.

Why is My Thyroid Still Not Normal?

Why Is My Thyroid Still Abnormal?

Reference Kent Holtorf Journal of Restorative Medicine 2014

Jan 19th, 2015

Standard medical practice measures two simple tests with your thyroid.   Your TSH (thyroid stimulating hormone) and your T4 (the circulating precursor to the active hormone T3).   Your doctor says, “You’re fine.”   You still feel crummy.   What’s going on?

Your doctor made the assumption that your blood test shows “normal” so you must be ok.   That assumption is based on the premise that if blood levels are ok, intracellular levels are also ok.   Aha!   Therein is the glitch. Transport of T4 into cells is not a passive subject.   There is much recent evidence that insulin resistance, diabetes, depression, chronic fatigue, high blood lipids, anxiety, dieting and plain old aging all contribute to reduced T4 transport into cells, while the pituitary is unaffected. In fact, the pituitary can continue to concentrate T4 up to as much as 600 times higher than peripheral tissues. The pituitary/hypothalamus combination is thereby not the best indicator of peripheral tissue function.   That’s what your doctor measures when she/he draws a TSH test. The TSH is what your pitutitary thinks you need. If it’s level is higher, it’s your pituitary saying you need more. If it’s lower, your pituitary says you have enough.

Transport of T4 into cells is not passive. That is the assumption your doctor made. It takes energy. Transporting T4 takes more energy than T3. If you are treated with pure T4, you might not be getting enough thyroid effect in your tissue. So, if you are cold, gaining weight, have muscle aches, decreased libido, weakness, water retention, depression, have low basal body temperature, all symptoms of being hypothyroid, you likely need to be treated with T3.

If this sounds like you, you may need to have some unique tests done. A much better assessment of your thyroid comes from testing your REVERSE T3 and calculating a T3 / rT3 ratio.   (Reverse T3 is a mirror image of T3 and basically blocks T3 from working – giving your body a valuable tool to adjust your energy metabolism up and down.)   High levels of rT3 are more likely due to reduced transport into the cell, and not due to increased T4 to rT3 conversion. So, a high rT3 is simply a good marker for lousy intracellular transport of T4. If you can’t transport T4 into the cell, you can’t make T3, and you feel tired, cold and achy.

Then, you should measure your Sex Hormone Binding Globulin (SHBG). SHBG is made in your liver in response to sufficient estrogen and sufficient intracellular T4 in the liver.   If women have a level above 70 nmol/L and men above 25 nmol/L, each has enough intracellular T4.

Read the whole article referenced above. Holtorf is one of your best thyroid educators.   The final kicker you will find is that dieting repeatedly changes the speed at which you transport T4 into the cell. It has been demonstrated that repeated dieting results in weight loss at half the rate, and weight gain at three times the normal rate unless thyroid hormone deficit is addressed. Hmmm.

WWW. What will work for me.   Weight loss is the holy grail of good health. But it messes up our thyroids and then we see our doctors who can’t figure out our problems. We feel cold. I’m checking rT3 and SHBG all the time now, and the light turns on when you see the results. It’s a much better set of tests than the simple TSH and T4.

Pop Quiz

  1. Reverse T3 is the mirror image of T3.   T or F

Perfect. True

  1. Reverse T3 reverses T3.   T or F

Again, on the money

  1. Our body balances T3 and rT3 intracellularly to deal with stress, which boomerangs on us in a highly stressed world, filled with dangerous foods. T or F

That’s about the sum of it

  1. Your pituitary gland reads blood levels of T4 accurately. T or F

Dead wrong. It can concentrate T4 and convert it to T3 many times more efficiently than local tissues

  1. The pituitary makes TSH which accurately reflects your bodies thyroid needs? T or F

T if your are taking the Internal Medicine exam, false if you are a human

  1. Sex Hormone Binding Globulin is an interesting adjunct measure of the accuracy of sufficient intracellular thyroid hormone activity. T or F





Brown Fat, Good Fat

Brown Fat, Good Fat

References:   Seale, Diabetes , van der Lans JCI Images from van der Lans, Cypess NEJM


It’s cold.   Wisconsin gets cold but this is extra lousy.   Last winter, it lasted for months.   Yet, my squirrels sit out there on the feeder and look toasty warm. How do they do it?     Brown fat.

Ever heard of brown fat?   You had a lot of it, once. As a newborn, a fair amount of your fat is brown fat.   It is stored in greatest amount between your shoulder blades. But check out the image link above for where PET scans show you to have fat. The amount regresses rapidly as you age, and adult humans don’t have much.   But, we keep ourselves warm all the time.   Squirrels and rodents in general have a lot of it.   They don’t have central heating in their dens.

What is important about brown fat? It has a unique protein in it that takes the energy you might normally convert into your internal gasoline called ATP, and instead makes it into heat.   That’s it. It simply turns on an internal heater that keeps you warmer without shivering. It’s called NST or Non Shivering Thermogenesis. Of course, you would be burning energy but you aren’t actively moving muscle to do it. Instead, you get all the energy turned into heat. The protein is called UnCoupling Protein or UCP-1, if you want jargon.    Regular skeletal muscle doesn’t have UCP. All it can do is shiver.

Now, Cypess in the NEJM reference above did a brilliant study showing that humans have a lot of brown fat. It shows up actively on PET scans, looking for cancer, as little hot spots.   But people who have been kept warm all the time, never need to develop their brown fat and have much, much less of it.

Hmmm. Can you develop your brown fat?   Can you get used to the cold?   Well, aren’t you feeling a bit more used to winter now than you used to be? Remember how cold you were that first day in November when we had the first return of the dreaded polar vortex? Yes, you do get used to the cold. You get acclimatized to it. It is a result of developing your brown fat.   How do we know that?

That what van Der Lans article is about.   He took 17 healthy young adults (23 +/- 3 years) and exposed them to 6 hours a day of temperature of 16 degrees celsius (60o F).     They did that for 10 days, then repeated PET scans on them to measure the change in their brown fat.   Results: a lot more brown fat, less shivering, less feeling cold,   Non-shivering thermogenesis or NST increased from 10% to 17% and their resting metabolic rate increased . Women went from 6.2 to 6.9 MJ/hour of resting metabolic rate.   Men went from 7.6 to 8.5 MJ.   They were acclimatized to the mildly cold temperature.

But did you get that?   You can turn up the rate at which your basal metabolism is cooking along. Could this be a way of losing weight and controlling diabetes? Yes! That’s what Seale’s article is about. As animals get fat with forced feeding experiments, they make more brown fat.   Their bodies are trying not to gain weight by having their NST turned on.   They stay hot all the time as an effort to get rid of their extra calories. Cold may be your friend. You just have to get used to it.

WWW. What will work for me.   Well, I’m out in this miserable cold every day, off and on.   I’ve not been hiking or walking as much as I would like because I don’t want to break an ankle. But I am turning our thermostat down at night.   I wish I could get a PET scan and see how much brown fat I had stored up.

Pop Quiz

  1. Brown fat is what keeps animals warm in winter – that’s how the squirrels are staying alive right now (-8o). T or F


  1. Humans have brown fat? T or F

Also true. Especially just as we are born.

  1. Most of our brown fat is between our shoulder blades?   T or F

True, also around our torsos

  1. We can make more brown fat by being exposed to 60o temperature for 10 days.   T or F


  1. Brown fat has been proven to help us lose weight? T or F

False. Not proven yet, but very intruiging.

  1. As animals get obese, they make more brown fat? T or F

Also true. And stay warmer – as though they were trying to get rid of the extra fat.

Astaxanthin for What Ails You

Astaxanthin: Antioxidant extraordinaire

Reference: Fransceschelli PLOS One Feb 2014

Astaxanthin has been getting press recently. It’s the pink color in salmon and shrimp, so it’s a naturally occurring compound related to the carotenoid family (carrots and other yellow vegetables.) It started emerging back in the 90’s. It’s use as an antioxidant has been found to be its ability to gobble up singlet oxygen. That’s the stuff that’s produced when mitochondria can’t grab onto a free electron and it spins off onto oxygen. That oxygen molecule acts like a tiny hand grenade, wreaking havoc inside the cell by disrupting membranes. The very nature of the cell is the creation of membranes to keep some things in one place, and other things in others. When those membranes get messed up, cellular function declines.

Astaxanthin has some unique properties. It can penetrate the blood brain barrier, which is relatively rare with many antioxidants. Oxidation in the vulnerable brain is part of what makes Alzheimer’s and Parkinson’s come about.   Nakagawa in the Br J Nutr in a randomized, placebo controlled trial showed that asthaxanthin reduced indicators of brain oxidative stress in just a few weeks. The neuroprotective effects have been shown in mice, in humans and in the research lab.

Benefits aren’t just on the brain. High blood pressure and heart disease are beginning to be thought of as dysfunction of the lining of arteries – endothelial dysfunction. The core of that dysfunction is the inability of the artery to relax. Renal transplant patients have it the worst.   So a randomized trial in transplant patient with anstxanthin showed significant benefit in arterial stretchiness – in the toughest patients of all. With the picking up of lipids in the artery, artery disease results in heart attack or stroke. Your natural prevention of heart disease comes about with higher HDL cholesterol. Astaxanthin has been shown to increase HDLs significantly.

Lots of folks have aches and pains and feel fatigued. When you snoop around with some lab, you find that their CRP is slightly elevated. CRP, C-reactive protein, is the common pathway in your body for inflammation. It turns on NFκB inside of cells which is the trigger to make a cell “act inflamed”. Inflammtion is the evil twin of oxidation when it comes to generating disease. Cutting to the chase and reducing CRP is a great way to improve fatigue and aches and pains from chronic, low grade inflammation.   What does astaxanthin do for that? It lowers CRP!

So asthaxanthin has lots of good properties. It would make sense to use it to help all those good qualities. Even Dr. Oz did a whole show on astaxanthin, touting all its benefits.  Is it safe? Yes, as far as anyone knows, there are precious few side effects. In fact, it seems to be synergistic with krill oil in lowering inflammation.   Those two get combined in products on the market now for joint health. And we didn’t mention folks getting help with their eyes, their skin….all the other places than antioxidants help. Astaxanthin has been touted as being 6,000 times as powerful as Vitamin C.   Let’s wait and see. There are detractors.

WWW. What will work for me.   I’m on a mission to lower CRP in folks, and in myself. I’ve done before and after testing in a bunch of people with modestly high CRP and found ways of reducing it. Pycnogenol and Krill oil have been remarkable actors in that line.   I’m adding astaxanthin to that list. 6-12 mg a day.


Pop Quiz

  1. Astaxanthin is the pink color in grapefruit? T or F

False – the pink in shrimp, lobster and other sea foods

  1. It has been shown to lower CRP in folks with elevated levels. T or F


  1. It works by gobbling up free oxygen radicals that act like hand grenades in your cells? T or F

True – making it your body’s bomb squad

  1. It can penetrate into brain tissue – not common amongst supplements. T or F


  1. It may play a role in helping Alzheimer’s and memory loss. T or F