Lithium: A mineral that affects mood, Alzheimer’s disease, obesity, and telomeres

I’ve written before on the topic of supplemental lithium orotate for mood, anxiety, and irritability. (Read the previous article here: A little lithium and B12 makes the world a happier place — for some.)

What about the effects of lithium as a mineral supplement on other aspects of health?

In reading studies on a wide range of other topics over the past three years, several links to lithium have popped up. Topics such as circadian rhythm dysfunction, Alzheimer’s disease, telomere length, type 2 diabetes, and obesity… not the subjects that I expected to lead me back to lithium!

The rest of this article lays out the evidence that increasingly shows the importance of this mineral in our health and longevity. I think it is important to examine the research and look at the long-term effects and safety questions that always come to mind when talking about lithium. There is such a stigma, at least in my mind, around lithium that I’ve hesitated at times to talk with friends and family about it – a hesitation that no one seems to have in recommending other minerals such as magnesium or potassium.

Lithium orotate supplements compared to prescription lithium carbonate:
I want to clarify before getting into the studies on lithium what ranges of dosages the studies are talking about. The prescription medication that most people are familiar with for bipolar disorder is usually in the form of lithium carbonate.

Standard doses of lithium carbonate are around 900-1200mg/day, although this can vary based on the individual. For lithium carbonate, there is about 18.8 mg of elemental lithium per 100mg of lithium carbonate. So a 900mg dose would give about 170mg elemental lithium.[ref]

Lithium orotate usually comes as a 120mg supplement that gives about 5mg of elemental lithium.

The amount of lithium that we get in foods and drinking water varies based on the mineral content of the soil, with estimates of .5 to 3mg per day. A provisional RDA of 1mg/day has been recommended. [ref]  So a 120mg lithium orotate (5mg elemental lithium) supplement would average around twice the normal daily consumption from food and water, while the prescription dosages are closer to 80 to 100 times normal daily intake.

Alzheimer’s Disease:
A new study came out in November 2017 on Alzheimer’s rates and natural lithium levels in the drinking water in Texas. In an article about the study (which is easier to read than the research paper:-), the lead author of the study explains the findings. Water samples from almost all of the counties in Texas were tested for their natural levels of the mineral lithium, which varies depending on the concentration in rock and soil.

The researchers found that Texas counties with higher levels of lithium in their groundwater had less of an increase in Alzheimer’s rates compared with counties that had lower levels of lithium. This isn’t a total surprise since previous studies had linked lithium to a decreased risk of dementia, but it is a great confirmation at a large scale population level.  A lot of the initial studies were observations linking bipolar patients taking large doses of lithium carbonate and having lower rates of dementia.

A sampling of other recent studies on lithium and Alzheimer’s disease:

  • A 2015 review in the Journal of Alzheimer’s Disease analyzed the data from three randomized placebo-controlled clinical trials of lithium for treating patients who had already been diagnosed with Alzheimer’s disease. The trials found that lithium “significantly decreased cognitive decline as compared to placebo”.
  • An October 2017 article in JAMA Psychiatry details a nationwide study in Denmark on the exposure to lithium in drinking water and the incidences of dementia.  This was a large study, with 73,000+ dementia patients and 733,000+ people without dementia as the control. The study found that there was a decreased rate of dementia in those people exposed to naturally higher levels of lithium in their water (measured since 1986).
  • A March 2018 animal study looked into the mechanisms of how lithium chloride lowers the risk of Alzheimer’s. It found that lithium chloride caused an increase in soluble β-amyloid clearance from the brain. In mice genetically bred to be a model of human Alzheimer’s, lithium chloride restored the clearance of soluble β-amyloid to the levels of normal mice. One big thing to note from this study is that lithium chloride did not affect β-amyloid that had formed plaque already.
  • A study in 2015 looked at the effects of microdoses of lithium on a mouse model of Alzheimer’s disease. The study found that small doses of lithium carbonate in the drinking water of mice carrying the genes for Alzheimer’s disease caused “decreased number of senile plaques, no neuronal loss in cortex and hippocampus and increased BDNF density in cortex, when compared to non-treated transgenic mice.” This was a follow-up study to the human study in 2013 which showed that microdoses of lithium stopped the cognitive decline in Alzheimer’s patients.

You may be wondering at this point why all doctors aren’t handing out low doses of lithium to everyone at risk for Alzheimer’s. I think the quick answer is that it isn’t the ‘standard of care’ with enough clinical trials backing it up. The cynical side of me also notes that lithium orotate (and aspartate) are cheap, over-the-counter supplements without pharmaceutical companies sponsoring huge trials and pushing doctors to prescribe them. There seems to be a couple of ‘novel’ low-dose formulations in the works by pharmaceutical companies, though. [ref][ref][ref]

Telomeres and aging:
Telomeres are the sequences of DNA that are found at the ends of each chromosome. This sequence protects the ends of the chromosome from deterioration. The common example given is to think of telomeres like the plastic on the end of shoelaces that protects the shoelace from fraying. When cells undergo cellular reproduction (mitosis), a little bit of the telomere is lost, and thus telomere length is considered a biomarker of cellular aging. Shorter telomere length is associated with several age-related chronic diseases including Alzheimer’s.

A recent transgenic mouse study found that lithium carbonate treatment leads to longer telomere length in mice that are bred to have Alzheimer’s disease. Interestingly, the normal mice had no effect on telomere length from lithium.  A meta-analysis of 13 studies found that Alzheimer’s patients have shorter telomeres.

A human study looked at telomere length in patients with bipolar disorder. The study found that patients with bipolar disorder (not on lithium) and their relatives had shorter telomeres lengths than healthy, unrelated people. More interestingly, patients with bipolar disorder who were lithium-treated had longer telomere length than patients with bipolar disorder who were not taking lithium as well as relatives of bipolar patients.

Telomere length is a new field of investigation for researchers looking into so many different topics of aging, longevity, and disease. I don’t think the handful of studies on telomere lengthening from lithium really lead to a conclusion yet; I look forward to seeing what future studies tell us on the topic.

Anti-Inflammatory action of lithium:
Lithium exerts some anti-inflammatory effects on the body as well as pro-inflammatory effects under some conditions. It has been known since the 1970’s that lithium inhibits prostaglandin synthesis and COX2 in some parts of the brain. While there is some debate on the topic, the majority of studies also point to lithium decreasing the production of TNF-α, a pro-inflammatory cytokine.[ref]

A recent cell study looked at the potential of lithium plus caffeine, theobromine, and catechin on the innate immune system and inflammation.  The results showed that stacking lithium with caffeine, theobromine, and catechin was more effective as an anti-inflammatory than using them separately.

Another recent study looked at the anti-inflammatory effects of lithium on cells containing the SOD2 genetic variant rs4880.  The study found that those with rs4880 alanine allele (GG for 23andMe) had more of an anti-inflammatory response than those with the valine allele (AA for 23andMe).  This was a cell study though, so it is hard to know how well this translates to the whole body.

Obesity and Type 2 Diabetes:
What surprised me about the Nov. 2017 study that I referenced above was that Texas counties with higher levels of lithium in their water also had lower levels of obesity and diabetes.  I was surprised by this because one of the side effects of long-term, high dose lithium carbonate usage is an increased risk of hypothyroidism and possible weight gain.

Part of the explanation for the high levels of lithium in water correlating to lower levels of obesity and diabetes may be due to the effects on circadian rhythm. Another possible connection between lithium, obesity, and T2D may be the effect on blood glucose levels. In mice, certain levels of lithium reduced non-fasting blood glucose levels.[ref]

How is lithium affecting our body and brain?
For a long time, it wasn’t really understood how lithium worked for bipolar patients. (Quite a few psychiatric medications have been used for decades without fully understanding the mechanisms by which they work – or don’t work – for people.) Studies over the past decade or two have shed light on the neurobiological mechanisms of lithium and genetic studies have increased that knowledge.

One effect of chronic, low-dose lithium is an increase in BDNF, which is a protein that promotes the growth of nerve cells.[ref]

The American Chemical Society published a great overview the topic in 2014, “Neuroprotective Effects of Lithium: Implications for the Treatment of Alzheimer’s Disease and Related Neurodegenerative Disorders“. One of the effects of lithium is its inhibition of GSK-3β (glycogen synthase kinase-3 beta), which is involved in neuronal cell development and energy metabolism. Genetic mutations of GSK-3β increase the risk of bipolar disease.

Lithium ions compete with sodium and magnesium ions in the body for binding sites in certain circumstances. Lithium’s inhibitory effect on GSK-3β is thought to be due, in part, to binding to a site that is normally occupied by magnesium. For a very thorough overview of the biochemical properties of lithium, including its effect on the activation energy of water within a cell and its effect on mitochondrial function, please read through “Towards a Unified Understanding of Lithium Action in Basic Biology and its Significance for Applied Biology“.

One action of GSK-3β is its inhibition of glycogen synthase, which is an enzyme involved in the reaction that takes excess glucose and turns it into glycogen for storage. Thus inhibiting GSK-3β increases glycogen synthesis and increases insulin sensitivity.[ref][ref]

GSK-3β and Circadian Rhythm:
Our body’s core circadian clock is run by a couple of core genes that are expressed during the day and a couple of core circadian genes that rise at night. It is this daily rise and fall of gene expression that then drives our internal daily cycles of waking and sleeping, temperature, and energy metabolism. GSK-3β is involved in phosphorylation of both the day and night core circadian genes.

Genetic variants that change our circadian rhythm are linked to increased risk for bipolar disorder. People with bipolar disorder who respond well to lithium therapy have changes in their circadian gene expression when they take lithium.[ref][ref][ref][ref]

Prevention of lead toxicity:
A recent article hypothesized that some of the benefits reported for higher lithium levels in the drinking water (lower suicide rate, lower homicide and crime rates) could be due to lithium mitigating the effects of lead toxicity. “Animal studies demonstrated that lithium pre-treatment mitigates lead toxicity.”

Toxicity of lithium:
Lithium is considered by some to be an essential trace element, and a complete elimination of lithium causes a decline in fertility, higher mortality rates, and behavioral abnormalities.[ref] But, like all substances, there is always a toxic upper limit.

Patients taking lithium carbonate or lithium chloride for mood stabilization show a variety of side effects, depending on dosing. Most patients taking prescription lithium carbonate get blood tests done at regular intervals to determine their serum lithium levels. Plasma lithium levels above 1.2 mM cause nausea, diarrhea, and tremor. [ref]  Other side effects noted by patients taking lithium chloride include increased thirst and urination, weight gain, and mental dullness. It was theorized that bipolar patients taking lithium may drink more calories due to increased thirst, thus causing weight gain.[ref] Other side-effects of higher doses of lithium include increased risk of kidney problems and interaction with hypothyroidism.

Lithium orotate, as a supplement, comes in much, much lower doses than the lithium in prescription lithium carbonate. There is one case report, though, of nausea and mild tremor from a teenager taking 18 tablets of a supplement that contained 100mg of lithium orotate.

Side effects of Lithium Orotate:
There aren’t any recent research studies or case reports (other than the one above) on lithium orotate side effects, so this section is n=1 personal experiences and internet hearsay. A couple of people that I’ve talked with have reported that lithium may make them tired or a little sleepy during the day, but this was pretty subjective and could have been due to other reasons. An article from a holistic doctor who suggests lithium orotate to most of his patients notes that very few have any side effects. He does suggest taking lithium orotate before bed instead of during the day. This makes sense in light of the circadian rhythm effects via GSK-3B inhibition. A study from 1986 on using lithium orotate for alcoholism listed minor side effects to the treatment (included more than just lithium orotate -e.g. low carb diet and other supplements) as loss of appetite, mild apathy, and muscle weakness. [ref]


If after reading through all the information about lithium orotate you want to add it to your supplement list, here are a couple of brands that are well regarded by my family: Weyland’s Lithium Orotate and Seeking Health Lithium Orotate.

As with any supplement, I suggest talking with your doctor if you are on medication or if pregnant or nursing.

The study on stacking lithium with caffeine, theobromine, and catechin for an increased anti-inflammatory effect was interesting. If you are considering this combo, a good source of theobromine is cacao nibs.  Catechins and caffeine are found in green tea.




Shining Genetic Light on Your Vitamin D Levels

Vitamin D is essential to so many processes in the body! It isn’t actually a vitamin at all, but a prohormone that is synthesized in the skin using cholesterol in a chemical reaction with UVB radiation from the sun.

Genes play a big role in your body’s vitamin D levels.  Read on to learn how to check your 23andMe results for your vitamin D genes.

Most think of vitamin D in regards to bone health because it regulates the uptake of calcium in our intestines, but it also acts in the nucleus of cells to regulate the production of hundreds of different enzymes, influencing health in a multitude of ways.

vitamin_D_levels_chartImportance of Vitamin D:
Vitamin D levels have been associated with a variety of chronic conditions, from mood disorders to cancer risk to immunity to bone density.  In general, higher vitamin D levels correspond to a lower risk of getting a variety of chronic diseases.

While low levels of vitamin D have been associated with higher risk of a bunch of chronic conditions, supplementing with vitamin D doesn’t always give impressive results in placebo-controlled studies. Do some research before jumping into supplementing with vitamin D.  For example, a recent clinical trial found little benefit for postmenopausal women when looking at bone mineral density, but the amount of vitamin D used in the trial may have been too small to get a result.

Part of the problem with looking at some of the research studies and clinical trials of vitamin D supplementation is that the doses used may have been too low.  A study came out a couple of years ago that claimed there was a statistical error in the calculation for the recommended daily intake of vitamin D. This error changed the supplemental doses needed by a factor of 10; instead of 600IU, some people may need 6000IU+ per day. More recent studies have backed this up, showing also that a person’s weight plays a big role in the amount of vitamin D needed for sufficiency.

Genes involved in converting vitamin D to the active form.

Conversion of vitamin D: from skin production to the active form
The form of vitamin D produced in our skin is the biologically inactive form, cholecalciferol or Vitamin D3; it is formed through a reaction between UVB rays from sunlight and cholesterol in our skin. Vitamin D3 must then be converted to the active form that our body uses.  The first step in the conversion takes place in the liver, where cholecalciferol is hydroxylated in the liver into calcifediol (25(OH)D) using an enzyme that is encoded by the gene CYP27A1. 25(OH)D can then be converted in the kidneys or macrophages into calcitriol, the biologically active form of vitamin D also known as 1,25(OH)2D.  This conversion takes place using an enzyme coded for by the gene CYP27B1.  For Vitamin D to be used in the nucleus of cells, it needs to be transported there by a binding protein that is coded for by the GC gene, and then it needs to bind to the vitamin D receptor, which is coded for by the VDR gene.

Vitamin D Genetic Variants:
Genetics can play a role in vitamin D levels in several ways, which makes sense when looking at the different steps involved in converting it to the active form which then acts on the vitamin D receptors in a cell.

GC Gene:
The vitamin D binding protein is coded for by the GC gene, and polymorphisms in the gene affect the total serum levels of 25(OH)D.  Many of the polymorphisms in the GC gene vary in different ethnic groups, and this is thought to be a big part of the difference in vitamin D levels among populations.

Check your 23andMe results for rs2282679 (v.4, v.5):
TT: Normal vitamin D levels [study]
GT: Somewhat lower total serum vitamin D levels
GG: Lower serum vitamin D levels[study][study]
Check your 23andMe results for rs7041 (v.4, v.5):
CC: Normal Vitamin D levels [study]
AC: Somewhat lower vitamin D levels[study]
AA: Lower Vitamin D levels [study][study]
Check your 23andMe results for rs12512631 (v4 only):
TT: normal
CT: normal
CC: increased vitamin D (both 25 and 1,25) levels. [ref]
Check your 23andMe results for rs1155563 (v4, v5):
TT: normal
CC:  significantly lower vitamin D levels[ref][ref]

VDR Gene:

After vitamin D (from sunlight, food or supplements) has gone through the conversion steps, the active form, calcitriol, can act on cells through the vitamin D receptor (VDR) which is a transcription factor that turns a gene on or off.  Vitamin D receptors control a variety of different functions including the activity of the immune system, skin, pancreas and bone tissue. There have been many, many studies on the VDR gene variants with most studies showing conflicting results. The VDR variants below are listed as ‘normal’ if they are found in the majority of the population. is a great place to search for specific reports on the health concerns that have been researched about these variants. Note that there are many popular websites online with reports on the VDR gene that are basing their + or – information on just a few older studies. [study]

Check your 23andMe results for rs731236 (v.4, v.5)  – VDR TaqI
GG: Normal  [study]
AA: VDR TaqI variant [study]
Check your 23andMe results for rs1544410 (v.4, v.5)  – VDR BsmI
CC: Normal bone mineral density [study]
AA: Carrier of BsmI variant, possible increased risk of low bone mineral density[study] [study]
Check your 23andMe results for rs2228570 (v.4 only) – VDR FokI
AA: normal
GG: carrier of FokI variants, pos. increased risk of fractures [study] [study] [study]
Check your 23andMe results for rs7975232 (v.4, v.5)
CC: Half the risk of dengue fever [study]
AA: normal risk of dengue fever

CYP2R1 Gene:
CYP2R1 is the gene that codes for the enzyme that converts cholecalciferol into calcifediol in the liver.  A fairly common genetic variant is associated with decreased vitamin D levels.

Check your 23andMe results for rs2060793 – CYP2R1 gene:
AA: Lower vitamin D levels  [study]
AG: Normal vitamin D levels
GG: Higher vitamin D levels
Check your 23andMe results for rs1562902 – CYP2R1 gene:
TT: Higher vitamin D levels  [study]
CC: Normal vitamin D levels

CYP27B1 Gene:

The second step in the conversion to the active form of vitamin D involves CYP27B1 as a catalyst for the conversion of calcifediol to calcitriol. While there are several common polymorphisms in CYP27B1 that have been studied in regards to vitamin D related conditions, none of them have been definitively shown to have an effect. A couple of rare mutations (listed below) of CYP27B1 do affect the conversion to the active form of vitamin D, and these mutations are linked to rickets, a disease caused by the lack of vitamin D in childhood.

Check your 23andMe results for rs28934607 – CYP27B1 gene:
AA: Pathogenic for Vitamin D related rickets  [ClinVar]
GG: Normal
Check your 23andMe results for rs28934605 – CYP27B1 gene:
TT: Pathogenic for Vitamin D related rickets  [ClinVar]
CC: Normal
Check your 23andMe results for rs28934604 – CYP27B1 gene:
TT: Pathogenic for Vitamin D related rickets  [ClinVar]
CC: Normal


Blue-blocking glasses at night help increase melatonin

Circadian Rhythm and Melatonin:
Sun exposure seems to be a double-edged sword these days, with UV light giving us vitamin D as well as increasing our risk for cancer. It makes you wonder why all of our ancestors didn’t end up with skin cancer without a handy bottle of sunscreen available. Turns out that our modern lifestyle with light at night (TV’s, tablets, phones, and LED light bulbs) has decreased our melatonin production. Melatonin at the right time plays a big role in both our circadian rhythm and our skins natural ability to withstand UV rays without creating skin cancer. Blocking blue light wavelengths at night increases melatonin production and should increase our skin’s ability to utilize UV rays for vitamin D production without the harmful effects. [study]  Read more about melatonin production, genetics, and blue light.

In addition to light at night, the time at which you eat also influences the circadian rhythm of your genes. A recent study showed that mice that eat at the wrong time (equivalent to humans eating at night) had increased skin damage from UV light. Basically, eating at the wrong time-shifted the phase of the circadian rhythm of skin genes to where UV damage would be less of a problem at night rather than during the day… and the sun doesn’t shine at night! So an easy ‘lifehack’ here would be to eat dinner earlier in the evening and don’t snack at night.

Food and Supplements:
Currently, in the US and Canada, vitamin D is added to milk.  Fatty fish, such as salmon, tuna, and mackerel, are also good sources of vitamin D.  Some types of mushrooms, when exposed to UV light, also contain vitamin D (as D2).

There are many vitamin D supplements available at stores and online.  Keep in mind that vitamin D is fat soluble and supplements usually contain oil such as soybean oil, which you may want to avoid. One that I like is this one with coconut oil on Amazon.  Again, the jury seems to still be out when it comes to a definitive recommendation on how much vitamin D is needed; you may find that your sun exposure is enough to keep your levels high enough.

Gut Microbiome:
The VDR gene, as well as other genes associated with vitamin D, plays a role in gut microbiome diversity.  VDR knockout mice had a 42% decrease in microbiome diversity index. That is pretty huge. Parabacteroides is one of the taxa that is affected by VDR genetic variants; it feeds on resistant starch, so adding in fiber and resistant starch might help encourage that microbe if you have decreased VDR. [study]

Testing Vitamin D levels:
If you haven’t recently tested your vitamin D level, it is an easy and fairly inexpensive blood test.  If you are in the US, there are lots of online sites where you can order lab tests without doctor’s order such as Walk-In labs. You can even order a vitamin D test from Amazon and test your levels at home.

More to Read:


Building Up Iron: Check your genes to see how iron affects your health

Hemochromatosis is a fairly common genetic disease that causes iron to build up in the body. Knowing that you carry the genetic variants for hemochromatosis can literally add years to your life since you can prevent the buildup of iron through giving blood.

This is a personal cause for me, and getting the word out to as many people as possible is important because this is one bit of genetic information that can make a huge impact on the quality of life.

23andMe and Ancestry genetic data can tell you if you likely carry the genetic variant for hemochromatosis. Read on to find out how to check your data…

Background: What is hemochromatosis?

“Hereditary (genetic) hemochromatosis (HHC) an inherited disorder of abnormal iron metabolism. Individuals with hereditary hemochromatosis absorb too much dietary iron. Once absorbed, the body does not have an efficient way of excreting iron excesses.  Over time, these excesses build a condition of iron overload, which is a toxic [sic] to cells. Glands and organs, including the liver, heart, pituitary, thyroid, pancreas, synovium (joints) and bone marrow burdened with excess iron cannot function properly.  Symptoms develop and the disease progresses.”  Iron Disorders Institute

The most common type of hemochromatosis is Type 1, or Classic, and is usually caused by variants in the HFE gene.

Check Your 23andMe results for rs1800562 (HFE C282Y) (v.4 and v.5)

  • AA: most common cause of hereditary hemochromatosis, highest ferritin levels
  • AG: increased ferritin levels, check to see if compound heterozygous with rs1799945
  • GG: normal/ wild-type

Check our 23andMe results for rs1799945 (HFE H63D) (v.4 and v.5)

  • GG: can cause (usually milder) hemochromatosis, increased ferritin levels
  • CG: somewhat higher ferritin levels, check to see if compound heterozygous with rs1800562
  • CC: normal / wild-type

Check our 23andMe results for rs1800730 (HFE S65C) (v. 4)

  • TT: can cause (usually milder) hemochromatosis, increased ferritin levels
  • AT: possibly increased ferritin levels
  • AA: normal / wild-type

Iron Buildup in those Heterozygous for Hemochromatosis gene variants:

So you’ve checked your genetic data and found that you are heterozygous (one variant) for one of the HFE variants… While most of the official hemochromatosis sites will say that you are ‘just a carrier’, in actuality, it could be causing problems, just not to the extreme extent that being homozygous for the variant could cause.

Doctors and researchers seem to be focused (rightly so) on the long-term consequences such as liver failure and heart failure of extreme iron overload. But if you know that you genetically susceptible to building up iron, you can take action to avoid the irritations that come with too much iron, such as random joint pain, fatigue, and/or abdominal pain.

Recent studies showing higher disease risk due to HFE variants:

  • increased risk of non-alcoholic fatty liver disease [ref][ref]
  • metabolic syndrome  [ref]
  • cardiovascular disease [ref] including women with heterozygous variants [ref]
  • slightly higher risk of cancer [ref] meta-study [ref] breast cancer[ref] liver[ref]
  • musculoskeletal problems (osteoarthritis like symptoms) [ref]
  • high blood pressure [ref]
  • hyperuricemia (gout) [ref]
  • lung fibrosis  [ref]
  • diabetes[ref]
  • cardiovascular disease in kidney disease patients [ref]
  • increased lead levels [ref] [ref]

The Iron Disorders Institute includes these signs and symptoms of too much iron: chronic fatigue, joint pain, abdominal pain, liver disease, diabetes, irregular heart rhythm, skin color change, hypothyroidism, enlarged spleen, elevated blood sugar and more.


Middle-aged men and menopausal women who are heterozygous or homozygous for any of the HFE variants, should, in my non-medical doctor opinion, go get their serum iron, TIBC, and ferritin levels checked or ask their doctor to test them. In the US, you can order your own labs online through places like Ordering serum iron w/ TBIC and ferritin should give you enough information to know if you are storing too much iron.

If you have slightly elevated iron levels, the simplest way to manage iron levels is to give blood! You will probably feel good, and you will definitely help out someone else with your blood donation. If your iron test levels are really high, go to a doctor. Seriously.

Natural Iron Chelators and Inhibitors:

In addition to giving blood, natural and pharmaceutical iron chelators have been used to reduce iron levels in the body.[ref]

Quercetin, a flavonoid found in fruits and vegetables, has been studied for its iron chelating properties.[ref]  A 2017 study on dendritic (immune system) cells found that quercetin “increase extracellular iron export, resulting in an overall decrease in the intracellular iron content and consequent diminished inflammatory abilities.” And a 2014 study on quercetin concluded: “Potentially, diets rich in polyphenols might be beneficial for patients groups at risk of iron loading by limiting the rate of intestinal iron absorption.” Foods high in quercetin include apples, dark cherries, tomatoes, capers, onions, and cranberries. Quercetin supplements including pure quercetin powder are also readily available.

Another flavonoid, rutin, has also been studied for its iron chelation properties.[ref]  A 2014 study in rats found: “Rutin administration to iron-overloaded rats resulted in significant decrease in serum total iron, TIBC, Tf, TS%, ferritin levels…”  Foods high in rutin include capers, black olives, buckwheat, asparagus, and berries.  Rutin is also available as a supplement and in bulk powder.

Okra: A 2015 study found that okra “dramatically decreases intracellular iron levels in H63D cells compared to untreated cells”.[ref]  Time to make some gumbo!

Dietary phenols such as EGCG from green tea and grape seed extract also have been shown to inhibit iron uptake in the intestinal cells.  [ref]

The jury is still out on curcumin.  In a double-blind, placebo-controlled, randomized, cross-over study, curcumin was found to decrease hepcidin and increase ferritin.[ref]  Other studies, though, refer to curcumin as a possible iron chelator.[ref]

Taurine, in a mouse model of hemochromatosis, was found to protect against liver damage from excess iron.  The study is worth reading and looking into if you are worried about iron-induced liver damage.

Iron Fortified Foods…May, or may not, be a problem for those carrying the hemochromatosis genetic variants.  In the US, white rice and refined wheat products are fortified with iron.

  • A Swedish study looked at the effect of iron-fortified foods on iron absorption in men with hemochromatosis.  The study found that eliminating iron fortification from foods significantly reduced the iron absorbed by the men in the study.  The study also found that the time needed between phlebotomy (to maintain proper iron levels in hemochromatosis patients) was increased significantly.
  • A US study in 2012, though, declared that there is no evidence that dietary iron content made a difference in ferritin concentration.  (I actually don’t agree with their ability to draw that conclusion based on the method of doing the study.)  Basically, they gave 200 people (homozygous for the HFE C282Y variant and high serum ferritin levels) surveys asking for information on the type of diet they had eaten for the last few years as well as alcohol intake.    Then they compared the survey data to their serum ferritin levels to look for a correlation and drew the conclusion that iron intake doesn’t impact hemochromatosis. [ref]
  • A few studies have looked at the impact of the overabundance of iron on obesity.   But while the risk for each of these diseases increases with higher ferritin levels, no one seems to be publishing studies showing that iron fortification is causing them.

The Science behind Iron Overload:

Hepcidin is the iron regulatory hormone produced by the liver. Hepcidin was discovered and named in 2000, and scientists have since figured out that it controls the regulation of iron in the body and responds to lipopolysaccharides to prevent iron-loving bacteria from reproducing rapidly.  [ref]

“Hereditary hemochromatosis is caused by a deficiency of the iron-regulatory hormone hepcidin (Ganz and Nemeth, 2011). Hepcidin is a 25 amino acid peptide secreted by hepatocytes. It controls iron concentrations in extracellular fluid and blood plasma by regulating the amount of ferroportin, the sole known cellular iron exporter. Ferroportin transports absorbed, recycled or stored iron from tissues into plasma (Donovan et al., 2005). Hepcidin binding to ferroportin triggers its degradation, resulting in the decreased transfer of iron to plasma and consequently hypoferremia (Nemeth et al., 2004b). During infections or in response to injection of microbial molecules, hepcidin production is greatly enhanced (Armitage et al., 2011; Rodriguez et al., 2014), stimulated by inflammatory cytokines including IL-6 (Nemeth et al., 2004a; Rodriguez et al., 2014) and possibly activin B (Besson-Fournier et al., 2012). It has been proposed that hepcidin-mediated hypoferremia functions as a host defense mechanism that evolved to restrict iron availability for pathogen growth (Drakesmith and Prentice, 2012; Ganz, 2009) but this has never been demonstrated. Hepcidin was also reported to have direct bactericidal activity in vitro (Krause et al., 2000; Park et al., 2001), but the effect is seen only at unphysiologically high concentrations.” –

Other Genes Involved:

Not everyone who is homozygous for the hemochromatosis variants will develop iron overload.  Diet and lifestyle play a role in the rate at which iron accumulates. Additionally, there are other genes that play a role in ferritin levels and iron levels in the body. Some of these are listed below:

  • BMP2 gene: rs235756 (v.4)-A allele is associated with higher ferritin levels with HFE variants (several studies) [ref] [ref]
  • BTBD9 gene: rs3923809 (v.4 and v.5)-G allele is associated with higher ferritin levels [ref]
  • HBS1L-MYB gene: rs4895441 (v.4 and v.5)- G allele protects against anemia [ref]
  • SLC40A1 gene: rs1439816 (not in 23andME v.4/v.5 data) – C allele may lead to more liver damage [ref] [ref]
  • TMPRSS6 gene: rs855791 (v.4 and v.5)- G allele associated with higher iron stores in men [ref
  • SLC40A1 gene: rs11568350 (not in 23andMe data) (Q248H) – leads to higher ferritin levels

Rare genetic forms of hemochromatosis (mostly non-HFE):

  • Hemochromatosis type 2A: listed in 23andMe as i5001498 (T is the risk allele)(v.4 and v.5)[ref]
  • Hemochromatosis type 2A: listed in 23andMe as i5001502 (A is the risk allele)(v.4 and v.5) [ref]
  • Hemochromatosis type 2A: listed in 23andMe as i5001501 (C is the risk allele)(v.4) [ref]
  • Hemochromatosis type 2A: listed in 23andMe as i5000096 (T is the risk allele)(v.4) [ref]
  • Hemochromatosis type 2A: listed in 23andMe as i5001503 (T is the risk allele)(v.4) [ref]
  • Hemochromatosis type 4: rs28939076 (T is the risk allele)(v.4) [ref]
  • Hemochromatosis type 4: i5006507 (T is the risk allele)(v.4)[ref]
  • Hemochromatosis type 4: i5006505 (A is the risk allele)(v.4)[ref]
  • Hemochromatosis type 2B: listed in 23andMe as i5003867 (T is the risk allele)(v.4) [ref]
  • Hemochromatosis type 1: i5012781 (C is the risk allele)(v.4) [ref]
  • Hemochromatosis type 1: i5012784 (C is the risk allele)(v.4) [ref]
  • Hemochromatosis type 1: rs1800562 (A is the risk allele) (v.4 and v.5) [ref]

Final thoughts…

Bloodletting in 1860. Public domain photo from Burns archive.

It hit me while researching all of this, that the bloodletters of yesteryear probably did some good for the minority of people who were overloaded with iron. Leeches to reduce blood and iron stores were probably effective against bacterial infections from iron-loving bacteria.

Fortification of iron into all wheat product in the US, which began in the 1940’s, is good for children and most women of childbearing age, but it adds to the iron overload burden for some men and older women.  When looking at the forced fortification of foods with iron and folic acid, it really does seem that the policymakers are focused on the majority, at the expense of a minority who genetically are harmed by it.  Since iron can takes decades to build up in the body, it may be that we are now seeing the consequences in the baby boomer generation.


More to read:




Thiamine – Genetic Variations in Need for B1

ThiamineThiamine (thiamin), also known as vitamin B1, is a water-soluble vitamin that serves as a cofactor in the metabolism of carbohydrates, branch chain amino acids, and fatty acids.  It is essential and needed in the production of ATP, which is used in every cell for energy. Severe deficiency of thiamin leads to beriberi, and less severe deficiency can cause fatigue, gut issues, headaches, and irritability.  [ref] [ref]

Food sources of thiamin include pork, enriched rice and wheat products, wheat germ, legumes, and sunflower seeds.  Daily recommended intake is around 1.2 – 2 mg per day. For someone on a  grain free diet who doesn’t eat a lot of pork, it may be worth tracking your intake for a week or so to make sure that you are getting enough thiamine. is an excellent and free way to keep track of your nutrient intake.

Thiamine transporter gene:

An SLC35F3 (thiamin transporter) variant is linked to hypertension. There have been other studies showing that thiamine supplementation reduces blood pressure in some, possibly due to the increase in pyruvic and lactic acid found in thiamine deficiency.[ref] [ref]

  • rs17514104 (not in 23andme) –  A is minor allele.  Those homozygous for the minor allele (AA), had a significant reduction in blood thiamine content and higher blood pressure. [ref]

SLC19A2 is the gene that codes for the Thiamine transporter 1. Mutations in this gene can cause thiamine-responsive megaloblastic anemia.

  • rs28937595 – AA is considered pathogenic for thiamin-responsive megaloblastic anemia.[ref]
  • rs121908540 – TT is considered pathogenic for thiamin-responsive megaloblastic anemia. (23andMe v5 only)

Rare Genetic Disorders:

Thiamine is also involved in several rare genetic disorders.  These are usually diagnosed in infants, but those who are heterozygous for the mutations listed below may want to look into these disorders and thiamine some more.

Pyruvate dehydrogenase complex deficiency (PHDC) is sometimes responsive to thiamine.

  • rs28933391 – AA is considered pathogenic for Pyruvate dehydrogenase deficiency.
  • rs28935769 – CC is considered pathogenic for pyruvate dehydrogenase deficiency.

An inborn error of branch chain amino acid metabolism, Maple syrup urine disease,  can be responsive to thiamine.  Mutations in the BCKDHB gene cause this error in BCAA metabolism.

  • i3002808–  CC is considered pathogenic for Maple Syrup Urine Disease[ref]
  • i4000422– AA is considered pathogenic for Maple Syrup Urine Disease [ref]
  • rs74103423– AA is considered pathogenic for Maple Syrup Urine Disease [ref]

More to read:

This post is just scratching the surface of all the ways that thiamine is used in the body.

Thiamine Supplements:

If you don’t eat a lot of foods that contain thiamine, there are thiamine supplements available.  Most good B-complexes, such as Jarrow B-Right, include thiamine.  There are also individual supplements, such as Seeking Health Thiamine.  If you don’t want the extra excipients in the capsules, PureBulk also sells thiamine powder.

Supplements for Methylation and More…

Reading the label on your supplements -- and getting rid of the surfactants.
Reading the label on your supplements — and getting rid of the surfactants.

I have ended up a cabinet full of bottles of all kinds of supplements!  Every time I learn about something new — methylfolate for MTHFR polymorphisms, hydroxycobalamin for MTRR polymorphisms, vitamin A because I don’t convert beta carotene, etc – off I go to order it from Amazon.

My latest deep-dive into the world of emulsifiers, surfactants, and the intestinal microbiome  has me questioning not only the ingredients in my previously “healthy” diet but also the excipients included in all of my supplements.  For all the talk on the internet about leaky gut and how good health starts with the microbiome, I had missed the boat on the fact that a lot of medications and supplements contain ingredients designed specifically to increase intestinal permeability.  The pharmaceutical industry calls them permeability enhancers and publishes lots of studies on how to loosen ‘tight junctions’.  While I understand the necessity for life changing drugs, I don’t think that I personally need to take a handful of permeability enhancers in the form of vitamin and mineral supplements each day.

While I’m convinced that carboxymethylcellulose (aka croscarmellose sodium, cellulose gum, CMC) is something that probably needs to be eliminated from everyone’s diet, I’m not yet sure about some of the other things in my supplement capsules.  For example, I haven’t been able to verify if hydroxypropyl methylcellulose affects the intestinal mucosa in the same deleterious ways that carboxymethylcellulose does.  Big words, and chemistry was a long time ago…  So why do I care?  Because hydroxypropyl methylcellulose (aka HPMC, vegetable cellulose, hypromellose, E464) is in the majority of my supplements in the form of vegetarian capsules.

Cleaning out the supplements with cellulose gum, carboxymethylcellulose, croscarmellose, polysorbate 80 (plus a few more excipients that I have reservations about but few studies to back up) left me with an almost empty cabinet.

One way around the extra additives in supplements is to buy the powdered version of the vitamin or mineral and create your own using gelatin capsules (or just mix the powder in some juice).  A couple of  brands that I’ve used and liked so far are Bulk Supplements and PureBulk.*  They can be ordered off of Amazon or through their own websites.

It is also a good idea to know what the supplements you take do in your body.  Take N-acetylecysteine (NAC) for example: It is a well known mucolytic (mucous thinner) that is used in studies to cause intestinal inflammation.  This study on how injury to the gut mucosal layer causes distant organ failure used NAC because “a 10% NAC solution is sufficient to injure the mucus layer by increasing gut permeability and decreasing gut mucosal hydrophobicity”.  I’m in no way advising you not to take NAC as a supplement if it works for you, but do take the time to look at the effects of NAC plus a surfactant and think about what you are combining together in your supplements.

I will read the labels before I buy another supplement!

Not A Doctor:
Do not take anything here as medical advice. Read, learn, and think for yourself.

Vitamin C Levels and Your Genes

As the weather here turns colder, thoughts turn to preventing colds and the flu.  My “go to” method of preventing sickness has always been by loading up on vitamin C, even though recent studies haven’t really supported the idea that vitamin C increase immune function. Like most nutrients, our genes play a role in how the nutrient is transported and used by the body.

So, what happens when we take or eat vitamin C? Our bodies have vitamin C transporters that are involved in the absorption of ascorbic acid (Vit. C) in the intestines.  Most mammals actually make vitamin C themselves, but humans can’t make vitamin C and have to rely on food sources.

Vitamin C has a variety of functions in the body.  It is an antioxidant, as well as a co-factor in many important enzyme reactions, including the synthesis of collagen, carnitine, and some neurotransmitters.

There are several major diseases associated with vitamin C levels as well as with genetic polymorphisms of the vitamin C transporters, SLC23A1 and SLC23A2:

  • Higher intake of vitamin C is associated with a reduced risk of cardiovascular disease. Higher plasma vitamin C levels (whether due to genetics or due to higher fruit and vegetable intake) is associated with a reduced risk of both heart disease and overall mortality. [ref]
  • Higher intake of vitamin C is associated with a reduced risk of stomach cancer.[ref] Stomach cancer is now the third leading cause of cancer deaths worldwide.[ref]

SLC23A1 and SLC23A2 are the genes that code for vitamin C transporters.  Variants of these genes affect the plasma levels of vitamin C.  All of these variants are very common; some are associated with higher plasma vitamin C concentrations and some with lower concentrations. You can check your 23andMe results for the variants by clicking the link below (if you have received your results after Aug. 2017, use the links that say v.5).

  • rs6133175 (v. 4 only):  Those with GG have (on average) 24% higher plasma vitamin C concentrations.[ref]
  • rs6053005 (v. 5 only): Those with TT genotype allele have (on average) 24% higher plasma vitamin C concentrations.[ref]
  • rs12479919 (v. 4 only): The T allele is associated with lower risk of gastric cancer, with those carrying the TT genotype at half the normal risk of gastric cancer.[ref]  [ref]  Since higher vitamin C levels = lower gastric cancer risk, it makes sense that those people with the T allele will have higher levels of vitamin C.[ref]
  • rs33972313 (v. 5 only):  Those with a T allele have an average decrease in plasma vitamin C concentration of 24%.[ref] Another study found that those with the C allele have a reduced risk of heart disease (implied that it is due to increased vitamin C transport) [ref]
  • rs10063949 (v. 4 and v.5): The C allele is associated with decreased vitamin C transport, and also with an increased risk of Crohn disease [ref]
  • rs1776964 (v. 4 only): A study found a  higher risk of heart disease in homozygous AA women regardless of vitamin C intake. [ref]

SLC2A1 (also known as GLUT1) is the gene that codes for the enzyme that transports glucose across the cell wall.  This same enzyme also transports the oxidized form of vitamin c, dehydroascorbic acid, into cells where it is then reduced to ascorbic acid. [ref]  While there are studies linking GLUT1 polymorphisms to diabetes in some populations, I didn’t find any relating to vitamin C levels in the cell.

I did find one interesting study that I wanted to share about vitamin C, glucose, and cancer:  A study in 2015 looked at the levels of glucose and ascorbic acid in thyroid cancer cells.  “The results showed that in thyroid cancer cells high glucose inhibits both transport of AA [ascorbic acid] and DHAA [dehydroascorbic acid]. Inhibition of vitamin C transport by glucose had a cytotoxic effect on the cells. However, stabilization of vitamin C in one of 2 forms (i.e., AA or DHAA) abolished this effect. These results suggest that cytotoxic effect is rather associated with extracellular accumulation of vitamin C and changes of its oxidation state than with intracellular level of ascorbate.”

Boosting your vitamin C intake: 

The US RDA for vitamin C is 60mg per day, which is a little above what is needed to prevent scurvy (46mg/day).  The Vitamin C Foundation recommends 3000 mg/day,[ref] and the Linus Pauling Institute recommends 400mg/day.  Vitamin C is a water-soluble vitamin and non-toxic, but you (and your bathroom) will know it if you exceed your personal bowel tolerance.

Excellent food sources of vitamin C include oranges, grapefruit, kiwi, strawberries, tomato and red peppers.

There are lots of options for vitamin C supplements including liposomal vitamin C. *

More to read:
Oregon State University: Vitamin C


Your need for riboflavin (B2): MTHFR, and other genetic variants

Riboflavin (Vitamin B2) supplements help some people with certain genetic polymorphisms.

Riboflavin (Vitamin B2) is a water-soluble vitamin that is a cofactor for many enzymes in the body.  To put it in simpler terms: riboflavin is vitally important!

Riboflavin is a ribose sugar bound to a flavin molecule.  It is the precursor to FMN (flavin mononucleotide) and FAD (flavin adenine dinucleotide), which are coenzymes involved in numerous vital functions in our bodies.  FAD is part of the Kreb’s cycle, producing energy in the mitochondria.  FAD is also involved in detoxification as a cofactor for some CYP450 enzymes as well as for glutathione recycling.[ref]

Riboflavin is found in dairy products, eggs, liver, enriched flour, and in minor amounts in many foods.  The US RDA is 1.6mg for adults, and most populations are estimated to meet this with their daily food consumption.  Dietary insufficiency can cause angular cheilitis (cracks at the corners of the mouth), anemia, burning mouth, sore throat, and vision issues.  [ref]


There are several genetic variants that can cause an increased need for riboflavin.


rs1801133 (C677T)   This fairly common variant causes a change in the shape of the MTHFR (methylenetetrahydrofolate reductase) protein that decreases its ability to bind to FAD.  [ref]

  • Riboflavin supplement lowered homocysteine levels in those with the AA genotype.  [ref][ref]
  • For those with the AA genotype and high blood pressure, riboflavin (1.6 mg/day) lowered systolic blood pressure by 5 – 13 mmHg.  [ref]

Gene: FMO3
FMO3 (flavin-containing monooxygenase 3) variants can cause a decrease in the FMO3 enzyme, which breaks down certain nitrogen-containing amines and some sulfur-containing compounds. FMO3 is the primary way that the body breaks down trimethylamine. Decreased FMO3 activity can cause an increase in trimethylamine, which causes a fishy smelling body odor.[ref]  Some people with mild FMO3 variants are helped with riboflavin.[ref]

rs1736557 (A is the risk allele)

  • This is listed as possibly a contributor to trimethylaminuria. [ref]  It is listed in ClinVar as both benign and pathogenic, so it may not be a problem for most people unless coupled with other variants.

rs2266782 (A is the risk allele)

  • reduced enzyme activity [ref]

rs909530 (Tis the risk allele, N285N)

  • reduced enzyme activity [ref]

rs2266780 (G is the risk allele, E308G)

  • reduced enzyme activity [ref]

rs61753344 (T is the risk allele)

  • causes varying degrees of trimethylaminuria [ref]


Part of the electron transport chain, problems with the ETFDH gene can cause MADD (multiple acyl-CoA dehydrogenase deficiency).  These are fairly rare mutations.

Gene: SLC52A3 (Riboflavin transporter, also known as C20Orf54)

i5008314  (rs267606684, A)

  • Pathogenic for Brown-Vialetto-Van Laere, a rare neurological condition which is often normalized by high dose riboflavin.  [ref]

Gene: DLD (Dihydrolipoamide dehydrogenase) [ref]

i5003700 (T)

  • Dihydrolipoamide Dehydrogenase Deficiency

Gene: SLC25A32 (encodes the mitochondrial FAD transporter)

rs147014855 (T)

  • T allele is listed in ClinVar as pathogenic for exercise intolerance that is responsive to riboflavin. [ref] [ref]

Diet and Supplements:

Additional Reading:


Genetics of Biotin Deficiency

Biotin, also known as vitamin B7 or vitamin H, is a cofactor which aids in the metabolism of fats, carbohydrates, and proteins.  Biotin deficiency due to diet is pretty rare, but eating raw egg whites for an extended period of time can deplete the body of biotin.  Foods that are high in biotin include egg yolks, nuts, meat, and dairy.

The Linus Pauling Institute website has a great in-depth review of biotin that includes information on deficiency symptoms and the function of this vitamin in the body.

Biotinidase Deficiency

Biotinidase is the enzyme that is involved in the extraction of biotin from food and also in the recycling of free biotin that has been used in another reaction in the body.

Profound biotinidase deficiency is defined as having less than 10% of normal enzyme activity, and partial biotinidase deficiency is defined as having between 10% and 30% of normal enzyme activity.

Note that not everyone with a BTD variant is affected by biotinidase deficiency[ref], but for most, a homozygous polymorphism will result in biotinidase deficiency.

So what happens if you are heterozygous for one of these polymorphisms?  There isn’t a lot of concrete information about it, but it seems that you would produce less of the biotinidase enzyme and thus get less biotin from food sources.  Biotin is a water soluble vitamin and not thought to be toxic at higher levels, so trying a biotin supplement may be worthwhile.

Check your genetic data: 

rs13078881 (C is the minor allele, also known as D444H)

  • Polymorphism reduces enzyme activity to just less than half of normal [ref]  If combined with other heterozygous BTD polymorphisms, it can result in partial or profound biotinidase deficiency.

The following SNPs are considered pathogenic for biotinidase deficiency for those who are homozygous for the minor allele.  (This is not a complete list.)

rs28934601 (G is the minor allele)

rs13073139 (A is the minor allele)

rs34885143 (A is the minor allele)

i6008460 (G is the minor allele)

i6008458 (A is the minor allele)

i6008480 (C is the minor allele)

i6008436 (C is the minor allele)


What to do with this information:

If you are heterozygous for one of the BTD polymorphisms and have symptoms of biotin deficiency, biotin supplements are readily available.  It is a water soluble vitamin and not known to be toxic.  Good food sources of biotin include nutritional yeast, which has over 200 mcg per 100g, and chicken liver which has 170 mcg per 130g. [ref]

Finding Quality Supplements

Having spent hours online reading Amazon reviews of supplements, I was happy to find a new, more analytical way to look at supplements recently.  A website called Lab Door is testing supplements to determine their contents and posting the results for free.

Supplements in the US are not regulated by the FDA for their purity or potency, so it is always a bit of a leap of faith when buying a new brand of a vitamin or mineral.  Lab Door is taking the mystery out of the buying process for quite a few popular supplements.  They publish their results for free and then make money on Amazon associate sales.

Lab Door has reports for the popular brands of specific vitamins such Vitamin C and D, and it also covers broader categories such as BCAA and protein powders.  Their report on fish oils includes heavy metal testing and a freshness test based on oxidation of the oil.  They don’t cover every supplement and miss quite a few that I would love to see, but it looks like they have quite a few more reports in the pipeline.

I have no affiliation with the company, just an appreciation of the information they are providing!

MTHFR, Depression, and Homocysteine Levels


An interesting study came out this year in the Journal of Clinical Psychiatry.  The study, Correlation of Clinical Response With Homocysteine Reduction During Therapy With Reduced B Vitamins in Patients With MDD Who Are Positive for MTHFR C677T or A1298C Polymorphism: A Randomized, Double-Bind, Placebo-Controlled Study, is available in full on the journal’s website.

The study included 330 adults with major depressive disorder who had either MTHFR C667T or A1298C variants.  (Check your status on these SNPS)   While the study report focuses on the marked reduction in homocysteine levels in the vitamin-treated group, it also reports very impressive reduction in depression scores.

The vitamin treated group were taking high doses of three forms of folate (1mg folic acid, 2.5 mg folinic acid, and 7mg of l-methylfolate), magnesium,  zinc, phosphotidylserine, and iron, along with microgram doses of the active forms of thiamine, B6, adenosyl-B12, NADH, and TMG.  Please see the study for the specific types of each of these vitamins and minerals.

The results of the 8 week trial showed that the vitamin treated group had an average reduction in homocysteine levels from 9.6 at baseline to 7.2 umol/L while the placebo group had a slight increase.

The study included a MADRS (Montgomery-Asberg Depression Rating Scale) score at baseline and after 8 weeks.  The vitamin treated group saw a decrease from an average score of 27 at baseline to 15 after 8 weeks, while the placebo group only saw a 1.3 point drop.

Again, I encourage you all to read through the study for yourselves, but to me, it seems to show a significant improvement for those with MTHFR variants and major depressive disorder.


Other recent studies on MTHFR, methylfolate, homocysteine, and depression:

  • Effectiveness of add-on l-methylfolate therapy in a complex psychiatric illness with MTHFR C677T genetic polymorphism. [link]
  • Association between MTHFR C677T polymorphism and depression: a meta-analysis in the Chinese population.  [link]
  • Homocysteine excess: delineating the possible mechanism of neurotoxicity and depression [link]
  • MTHFR: Genetic variants, expression analysis and COMT interaction in major depressive disorder [link]