However obscure, it’s time manganese got on your radar!

Of the 15 nutritional elements that I focus on in a Hair Tissue Mineral Analysis, I’ve dabbled in supplementing most of them (with only very limited experiments with phosphorous, chromium, and iron). I try not to make suggestions for mineral balancing based on intellectual knowledge alone. I believe there’s more value in suggesting things I have personally tried and have a somatic experience of – not because my body will react or need that mineral in the same way as your body will, but because I feel like it’s important to get to know these elements in a personal, intimate way if I am to advocate them.

I like experimenting. And there is no mineral that has had such a profound somatic effect on my body than manganese. Manganese has so benefitted me that I now consider it to be part of a holy trinity of the minerals that I adore most – along with copper and zinc, of course. So in this post I want to share with you why copper, zinc and manganese work so well together to heal migraine , and how their synergy is nothing short of miraculous when it comes to reducing hypoxia (tissue oxygen deficiency), and hence migraine.

Recently I’ve had two coaching clients with very low manganese levels in their HTMA. One of them had a history of lyme disease, a pathogen known to deplete the body’s stores of manganese. The other client has a very short follicular phase, which could be caused in part by her low manganese status.

Manganese basics

Manganese is sufficiently overlooked in the treatment of migraine that if you Google “manganese + migraine” it will think you’re asking about magnesium and migraine and show you those links instead. This is unfortunate, because manganese is so important for a wide variety of functions, many of them related to migraine.

The highest concentrations of manganese are found in the liver, thyroid, pituitary, pancreas, kidneys, and bone.

I’ll be putting the benefits of manganese most related to migraine towards the top of the list.

  • Manganese helps to reduce hypoxia. One of the dominant theories of migraine causality is that migraine results from cortical spreading depression, but other researchers have found cortical spreading depression to be caused by and coinciding with tissue hypoxia. I consider hypoxia (reduced oxygen) to be one fo the root causes of migraine. Manganese helps to reduce hypoxia by increasing the antioxidant MnSOD, which in turn lowers Hypoxia-inducible factor-1 (HIF-1), a transcription factor that governs cellular responses to reduced O2 availability.
  • Manganese has been shown to increase zinc ion transport via a protein known as ZIP8 (source), although in rats. If you’ve read any of my other blog posts on the importance of zinc for migraine, you’ll understand why manganese’s ability to increase zinc will in turn help to decrease brain inflammation from glutamate overload. Conversely, an excess of zinc intake decreases liver stores of manganese, at least in rats (source).
  • Manganese also directly helps to reduce glutamate load (and not just by way of increasing zinc). It does so by converting glutamate to glutamine via the glutamine synthetase enzyme (source) – although too much manganese can also cause excitotoxicity. For more on the role of glutamate in migraine, see this blog post.
  • Manganese plays a role in hormonal regulation and reproductive function as manganese is involved in pituitary secretion of luteinizing hormone. Manganese deficiency is characterized by defective (often early) ovulation. Any woman who has hormonal migraine will want to look at her manganese status for this reason.
  • A deficiency of manganese may lead to an ammonium toxicity, since it is required for the conversion of ammonium ions to urea (source). Ammonium toxicity is directly implicated in brain swelling or encephalopathy, ie, migraine.
  • Adrenal hormones play a role in tissue distribution and metabolism of manganese (source). Adrenal health and regulation is essential for those with migraine, because the adrenal glands and their steroid hormones play such a huge role in the body’s ability to retain essential minerals and regulate sleep and the stress response. Therefore those with compromised adrenals may not be distributing and metabolizing manganese efficiently.
  • Manganese is involved in the formation of thyroxin (source). Because women with migraines generally tend to have thyroid imbalances as well, improved manganese status may also help to resolve migraines by way of its effect on thyroid function. Manganese is required by the body to produce superoxide, which in turn makes hydrogen peroxide to make thyroid hormone.
  • Manganese shows a synergistic relationship with choline. A deficiency of either or both may lead to abnormal mitochondrial and cell membrane integrity (source).
  • Manganese deficiencies play a role in cartilaginous and collagen disorders (hypermobility) as well as bone density. Many migraineurs suffer from connective tissue disorders.
  • Manganese plays a role in insulin secretion and glucose metabolism (source). With their tendency towards low blood sugar, migraineurs may benefit from the blood-sugar regulating effects of manganese.
  • Genes play a role in manganese deficiency. SLC39A8 deficiency is an inborn error of metabolism that is caused by impaired function of manganese metabolism in humans, including glycolisation. Hypoglycosylation disorders have been linked with migraine, and treated with both manganese and galactose administration.

Enter superoxide dismutase (SOD) and MnSOD

There’s a reason that I put manganese’s ability to reduce hypoxia at the top of the previous list of reasons for why it is such a powerful mineral to reduce migraine. Manganese decreases hypoxia and increases oxygen to the body’s tissues by way of its role in the antioxidant MnSOD. Superoxide dismutatses are enzymes that transforms the damaging superoxide (O2-) free radical into oxygen (O2 or hydrogen peroxide (H2O2). It is protective against oxidative damage, inflammatory cytokines, and ionizing radiation.

There are three types of SOD:

  • SOD1 is found in the cellular fluid and is copper and zinc-dependent
  • SOD2 is found in the mitochonria and is manganese-dependent
  • SOD3 is found outside the cell and is also copper and zinc-dependent

Are you starting to get the picture for why copper zinc and manganese are all needed for antioxidant health? MnSOD or SOD2 is considered one of the most important of the SOD family because it works on the level of the mitochonrion, or the powerhouse of the cells.

Manganese superoxide dismutase (MnSOD) is the principal antioxidant enzyme in the mitochondria. Because mitochondria consume over 90% of the oxygen used by cells, they are especially vulnerable to oxidative stress. The superoxide radical is one of the reactive oxygen species produced in mitochondria during ATP synthesis. MnSOD catalyzes the conversion of superoxide radicals to hydrogen peroxide, which can be reduced to water by other antioxidant enzymes. (Source)

SOD is only one of many important antioxidants in the body (others are NAD, glutathione, vitamin C and vitamin E). But it plays an absolutely crucial role in recovery for migraineurs. And without sufficient manganese, SOD just can’t work properly.

Manganese and diet

Although it is generally assumed that manganese deficiency is rare, in some individuals, genetic factors as well as the level of inflammation a person is experiencing in their body plays a role in whether what their diet is offering them is sufficient or not.

In his article on manganese, David Watts, PhD, of Trace Elements Laboratory’s states that:

  • Manganese is high in plant-based foods, especially nuts, beans, grains, and leafy vegetables.
  • While vegetarian food sources are high in manganese, it has been found that meat, which is a low source of manganese, enhances the bioavailability of this mineral in the diet. People who eat higher protein levels tend to have a more positive balance of manganese than those on a low protein diet.
  • Manganese is absorbed through the small intestine, but due to the nature of mineral dynamics, its absorption can be negatively affected by the presence of calcium, phosphorous, and soy protein.
  • Alcohol increases both absorption of manganese and the levels of manganese retained in the liver.

My experience with manganese and scoliosis

What’s truly elegant about mineral balancing is that each mineral is needed to spark hundreds of enzymatic processes, so inadvertently, when a mineral gets balanced, multiple areas of the body get healed. In my case, manganese has been hugely helpful in healing my pattern of scoliosis, which has been a nice accidental side-effect of using it to support my mitochondrial health.

As my tendons have become stronger, I have watched with wonder as the alignment of the bones my tendons are attached to have been readjusting themselves, from my ankles to my knees all the way up into my hips and even my wrists and cranial bones. To be able to observe the sequence of healing as it unfolds has given me much deeper insight into my pattern of scoliosis, which I believe in my case was a congenital case of midline instability that went back to my development in the womb (and which got exacerbated in my teen years).

After noticing these changes, I decided to see if researchers had found a link between manganese and scoliosis. They have:

An inability to properly use the essential mineral manganese could be to blame for some cases of severe scoliosis, according to a new study from Washington University School of Medicine in St. Louis.

Nobody knows why some children’s backs start to curve to one side just as they hit puberty. Most children diagnosed with scoliosis, or curvature of the spine, have no known risk factors.

A new study suggests that the body’s inability to fully utilize the essential dietary mineral manganese might be to blame for some cases of severe scoliosis. Researchers at Washington University School of Medicine in St. Louis have found that children with severe scoliosis are twice as likely as children without the disease to carry a gene variant that makes it hard for their cells to take in and use manganese. Manganese is required for growing bones and cartilage.

Our study links a common disease – scoliosis – to something that’s potentially modifiable in the diet,” said senior author Christina Gurnett, MD, PhD, a professor of neurology, of orthopedic surgery and of pediatrics. “But we don’t want people to go out right now and start manganese supplements, because we already know that too much manganese can be harmful. (Source)

In my case, supplementing with manganese has also been a good example of the limitations of an HTMA (or really, any lab test) to tell me I needed more of this vital mineral. This is because how well enzymes function doesn’t have only to do with your absolute values of a given nutrient, but rather how efficient your genetic SNPs are. In some cases, people can have inefficient enzyme function and need more of a mineral for their enzymes to function even when they are not deficient on an absolute level. (HTMA is still an excellent tool for detecting toxicities and absolute deficiencies).

In my case, my HTMA showed sufficient levels of manganese, but from what I have read about certain gene SNPs related to scoliosis, the issue again is inefficient enzyme function even in the presence of normal levels.

I haven’t had my genes tested, but I suspect I may have an SLC39A8 gene variant, or another unknown variant, leading me to benefit from supplemental manganese. A study published in Nature Communications states:

Researchers found a variant in the gene SLC39A8 in only 6 percent of the healthy children but 12 percent of the children with severe scoliosis. A second analysis in a separate group of 1,095 healthy children and 841 children with moderate to severe scoliosis also found that children with scoliosis were about twice as likely to carry the variant. When the researchers bred zebrafish with a disabled SLC39A8 gene, the fish developed movement and skeletal abnormalities, including curves in their spines.

I supplement very modestly with manganese (as I do with all minerals), but it is totally profound to watch the changes that have been occurring on the level of my connective-tissue health since taking manganese.

Cautions and considerations with manganese supplementation

In terms of eliminating migraines, the primary cautions to consider in taking manganese without causing worse problems due to the dynamic relationship that minerals have with each other, is to consider that manganese is a copper antagonist. That means that for people who are already low in copper, manganese supplementation could cause an exacerbation of histamine sensitivity and weakening of elastin if taken without copper.

Copper zinc and manganese all need to be taken in balance to each other. And because manganese optimizes zinc transport, it can reduce the need to supplement zinc at the levels many practitioners are suggesting.

Below are a few more considerations regarding manganese supplementation:

  • Manganese lowers lead and cadmium, as well as copper, calcium, D, E, and b12.
  • Nutrients synergistic with manganese include the minerals potassium, zinc, sodium, magnesium, iron, phosphorus, and the vitamins A, E, B1, B3, B5, and B6 (source).
  • Maganese can be toxic at elevated levels. Toxicity symptoms include asthenia, anorexia, muscular pains, mental excitement, hallucinations, unaccountable laughter, impaired memory, and compulsive actions, speech disorders, clumsy movements, abnormal gait, poor balance, hyperreflexia in the lower limbs, and fine tremors (source).
  • On an HTMA, excess manganese is also often seen alongside iron toxicity. In this situation, the manganese is a secondary elevation and probably adaptation due to excess iron retention (source).

To sum up . . .

Like all minerals, manganese is a powerful catalyst for very important enzymes that help us to regulate many important bodily functions like hormonal balance, blood sugar regulation, connective tissue integrity, and more. But it is manganese’s important role in reducing hypoxia and improving mitochondrial health that I find to be the most exciting features of manganese. (Or its ability to support tendon and bone health if you have scoliosis, which many migraineurs do).

Manganese works wonderfully in tandem with zinc and copper, too. So if you’d like to get these minerals balanced according to your own metabolism and in consideration of your own hormonal and mineral patterns, consider coaching and Hair Tissue Mineral Analysis. I offer a free 30 minute discovery call!