[A] little background first, I’ve been really ill for around 13 years. After identifying the problem as heavy metal toxicity, I spent a year and a half doing chelation and methylation treatments. My expected recovery did not materialize however – I experience some improvements but became sicker in other ways. I think this is because my liver and kidneys couldn’t cope with the burden placed on them by the onslaught of detoxification. That makes sense if you consider that my toxicity probably developed as a result of a dysfunctional liver in the first place.
Going beyond toxic exposure, it’s genetic flaws – SNPs in these genes that probably made my liver the weak link:
- PEMT – “studies have recently shown that because of common genetic polymorphisms, choline deficiency is a widespread problem. Men, postmenopausal women, and premenopausal women with PEMT SNPs need to increase choline intake in the diet to offset elevated risk of liver dysfunction.”
- CYP – Cytochrome P450 enzymes are present in most tissues of the body, and play important roles in hormone synthesis and breakdown including estrogen and testosterone synthesis and metabolism, cholesterol synthesis, and vitamin D metabolism. Cytochrome P450 enzymes also function to metabolize potentially toxic compounds, including drugs and products of endogenous metabolism such as bilirubin, principally in the liver.
- AHCY, BHMT, MTHFD1, MTHFR, MTHFS – all of these genes are involved in the process described here for the more famous MTHFR: The MTHFR gene produces the MTHFR enzyme. The MTHFR enzyme works with the folate vitamins (B9, folic acid), breaking it down from 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate which helps convert the amino acid homocysteine down to another essential amino acid, methionine, which is used by your body to make proteins, utilize antioxidants, and to assist your liver to process fats.
It was a weird accident that put me on this trail.
Since I know that I have many genetic methylation defects, I searched for a connection with the liver. At first, I could not find any correlation between methylation and the liver. But a funny thing happened yesterday – I accidentally took my wife’s breakfast supplements which included 25 µg of T3 and 1.6 g of methyl folate. I think this is the first time that I use the F word in front of my kids!!! T3 and folate are both like kryptonite for me.
So I tried to vomit it out but wasn’t very successful. Fortunately, the aftermath really wasn’t anywhere near what I thought it might be – I was extra spaced out and fatigued after a couple hours. But I started researching liver function and folate and guess what? Turns out there is a really strong connection.
Folic acid increases bile flow and bile acid synthesis.
Today, a little more than 24 hours after my unplanned T3 and folate surge, I notice my stool is much darker than usual. So I go look up ‘folate bile flow’ and find this study saying:
Folic acid increases bile flow, bile acid synthesis from cholesterol, and bile acid excretion via feces, thus provoking a decrease in serum and hepatic cholesterol. However none of these actions were observed in supplemented control rats. This, therefore, could be yet another beneficial effect of folic acid on alcoholic patients.
Okay those are alcoholic rats, but still… then there is also this:
The liver contains about 50% of the body stores of folate.
Doesn’t it stand to reason, that if you have a deficiency of folate, you’ve got a liver that may not function properly? I think it also explains why increasing my folate intake, has made me feel so crappy – if my liver starts producing more bile, I’m immediately increasing my detox rate. I think that’s why it makes me feel like I’ve got the flu.
Next I started looking at how liver function and thyroid function might be related.
I knew that methylation support often improves thyroid function rapidly according to Fred. So I knew there was at least a possible indirect connection with my genetic flaws. Guess what? It gets much more interesting…
T3 stimulates liver growth and regeneration!
Sounds like a possible treatment for me. Reminds me that I never did get around to trying T3 at 5 AM as some had recommended.
Recent work investigating the use of tri‐iodothyronine as a hepatic growth factor has shown it to be a primary mitogen for the liver in animal models (i.e. it induces hepatocyte proliferation and increases liver mass when administered at high doses in the absence of hepatic injury).94
So if T3 stimulates liver growth, maybe low thyroid could also cause your liver to slow down its detoxification enough to cause serious health problems. And vice versa? Could a malfunctioning liver could probably give you hypothyroidism? I seem to have all these problems together, so why not.
Here’s why troubleshooting the liver and methylation is so difficult.
You would think that anyone with deficiencies in methylfolate, mb12 and choline would feel great as soon as we supplemented those nutrients. But, many of us feel terrible instead. So the easiest, most logical thing to do is to think that we are allergic to the very things we need to heal. I think there are two reasons why we have bad reactions to the supplements we need:
- First, if our liver is overloaded with toxins and choked up with toxic liver stones, any increase in function is going to release toxic garbage into our intestines through increased bile flow. Some of those toxins are unavoidably absorbed back into the bloodstream sickening us.
- Second, our bodies are like old rusty, unmaintained cars that will run okay on back roads but would shake apart on the freeway. You don’t drive a car like that 70 miles an hour without expecting trouble. There are hundreds of systems in our bodies that need to be slowly brought back to life in concert. Pushing just one system can overload the rest.
One last possible cause for liver weakness – has fish oil been damaging my liver?
I’ve also been getting some help from liver flush guru, Michael Handels who sent me a link to this article about possible dangers of fish oil:
The most popular way of arguing that fish oil will prevent heart disease is to show that it lowers blood lipids, continuing the old approach of the American Heart Association’s “heart protective diet.” Unfortunately for that argument, it’s now known that the triglycerides in the blood are decreased because of the fish oil’s toxic effects on the liver (Hagve and Christophersen, 1988; Ritskes-Hoitinga, et al., 1998). In experiments with rats, EPA and DHA lowered blood lipids only when given to rats that had been fed, in which case the fats were incorporated into tissues, and suppressed mitochondrial respiration (Osmundsen, et al., 1998).
I was taking fish oil because of it supposed benefits to the mitochondria, but Ray Peat says it’s the opposite:
The acrolein which is released during lipid peroxidation inhibits mitochondrial function by poisoning the crucial respiratory enzyme, cytochrome oxidase, resulting in a decreased ability to produce energy (Picklo and Montine, 2001).
If my fatigue and energy depletion truly stems from a liver that doesn’t supply glycogen, then according to Ray Peat, fish oil may be making my situation much worse:
The reactions of three types of cell–vascular endothelium, nerve cells, and thymus cells–to the PUFA will illustrate some of the important processes involved in their toxicity.
When the body doesn’t have enough glucose, free fatty acids are released from the tissues, and their oxidation blocks the oxidation of glucose even when it becomes available from the breakdown of protein caused by cortisol, which is released during glucose deprivation. Cells of the thymus are sensitive to glucose deprivation, and even in the presence of glucose, cortisol prevents them from using glucose, causing them to take up fatty acids. The thymic cells die easily when exposed either to excess cortisol, or deficient glucose. The polyunsaturated fatty acids linoleate, arachidonate, and eicosapentaenoic, are especially toxic to thymic cells by preventing their inactivation of cortisol, increasing its action.
This is really very technical, and I think you could summarize it by saying that fish oil is toxic to the brain and other organs:
Acrolein, produced from the decomposing “fish oils” in the brain, is probably the most reactive product of lipid peroxidation in the brain, and so would be likely to cause the glycation of lysine in the plaque-forming proteins.
These toxic effects of acrolein in the brain are analogous to the multitude of toxic effects of the omega-3 fatty acids and their breakdown products in all of the other organs and tissues of the body. Cancer cells are unusual in their degree of resistance to the lethal actions of the lipid peroxides, but the inflammatory effects of the highly unsaturated fatty acids are now widely recognized to be essentially involved in the process of cancerization (my newsletters on cancer and leakiness discuss some of the ways the fats are involved in tumor development).
The fats that we synthesize from sugar, or coconut oil, or oleic acid, the omega-9 series, are protective against the inflammatory PUFA, in some cases more effective even than vitamin E.
Here’s what this means for your diet (from Paleo Leap):
A good rule of thumb would be to consume no more than 4% of your calories as Omega-6 fat and around as much Omega-3 fat. Practically, this means cutting off all vegetable oils except coconut oil, olive oil and palm oil, cooking with low PUFA oils and fats like clarified butter, coconut oil and tallow and eating only limited amounts of the nuts that are high in Omega-6 fat.
Before the liver can heal, the kidneys must be functioning well.
From Michael:
The order of Hulda Clarks protocols are extremely important. I think a lot of people skip ahead and do chelation and liver cleansing first, which is a HUGE mistake. Huge, huge mistake. If the kidneys cannot eliminate the toxins released by these other things, then they just get recirculated and re deposited. It is what I did and I paid a big price for it.
Here is a little evidence for that from Ray Peat:
One of the essential protective functions that decline with aging is the liver’s ability to detoxify chemicals, by combining them with glucuronic acid, making them water soluble so that they can be excreted in the urine.