English corner: High dose manganese

English corner: High dose manganese (Mn)
Manganese inhibits CoQ10 so that mitochondrial respiration fails
The singular mechanism of manganese (Mn) toxicity is that it inhibits the synthesis of Co-Q10. (1) The effects of excess Mn (2) can all easily be synthesized into a mechanism where manganese inhibits Co-Q7 enzyme, Co-Q10 levels fall, antioxidant defense fails, mitochondrial respiration fails, and ATP production stops, all because CoQ10 levels dropped. (3)
Co-Q10 as membrane stabiliziter
Coenzyme Q-10 (Co-Q10 or ubiquinol) is a quinone that functions as an electron transfer agent, in the cells, between cytochromes in the Krebs cycle (cellular energy). If you lack Co-Q10, your body's most important source of cellular energy is depleted, and many medical conditions are then aggravated. (4)
Too much of a good thing is bad: U-shape overload
We are not all equal in burning Co-Q10. In fact, there are many “matters” where Co-Q10 could be useful. Some people with Co-Q10 synthesis gene mutation could require doses as high as 3 000 mg per day. This gene mutation is much more common than homozygosity (30 – 60% with 2 or 1 gene modified).
Co-Q10 supplement, in 26 trials, shows that 100-200 milligrams per day lowers blood pressure, but that 400 milligrams per day raises blood pressure on average. (3)
Glycemic control shows a similar U-shaped curve, and antioxidant status is best optimized at a dose of only 100-150 milligrams.
By contrast, an analysis of 13 trials found that fatigue responds best when the dose is higher, even up to 500 milligrams a day.
These conflicting results emphasize how essential it is to figure out for each person what dose is needed, and whether Co-Q10 is needed at all. So, high dose Co-Q10 could overload numerous biochemical pathways in someone who doesn’t need it, creating all sorts of imbalances.
To make matters worse, supplementing mice with CoQ10 across the entire length of their adulthood worsens age-related hearing loss and impairs spatial learning and memory.
On the other hand, we synthesize CoQ10 ourselves. If we are making enough of our own, isn’t CoQ10 a waste of money?
Back to manganese
Case-report (Luc): Optimal Ferritin Levels May Surprise You
One of my previous blood test indicated I was high in iron. Ferritin 245 μg/L. Best between 40 – 80 ng/ml. Not the “healthy RDA range” (30 – 240 ng/ml).
I decided to donate blood. 5 years later, I’m 89.9.
Note:  About [Vous devez être inscrit et connecté pour voir ce lien] are at least heterozygous for a genetic impairment in iron handling.   
Unfortunately you can’t just donate blood and think everything will be all right. Why?
90% of your iron is stored in your blood, but most of your manganese is stored in your liver. When you donate blood, your iron status declines. Fine if overloaded but this makes you more vulnerable to manganese toxicity. I explain.
If you eat less red meat, your restrict iron in your food. But if you eat banana, nuts, legumes or oat on a regular base, if you drink tea or hibiscus tisane, you lift manganese sources. I repeat: If you eat less meat and more veggies to avoid heme iron, you will drown yourself in potentially toxic manganese situation ( > 8-11 mg ).
Manganese overload
If you donate blood to clear iron, you will not clear your manganese, and your absorption of manganese from food will increase. If you restrict dietary iron, your balance between iron / manganese from food will increase.
So, blood donation will make you more subject to unbalance. I’m not saying you need stopping blood donation. But you’d better diminish manganese food sources after blood donation, until you remake blood cells. That’s a question of proportion.
Normal levels of manganese will leave a healthy person's body through their feces after a few days. The liver removes excess manganese from the blood, and this manganese is then excreted into the bile and feces (80% in feces and 20% in urine). (5)
Absorption & Elimination
Of the manganese you consume in food, only 1 – 5% is absorbed into the blood. This level is tightly regulated based on the amount of Mn in your diet. You will absorb less if you’re eating a lot of manganese-rich food [[Vous devez être inscrit et connecté pour voir ce lien]].
The End-Point
No need to worry about unless you lack ferritin and you eat too many rich-foods in Mo. Except for people with an already low ferritin level, as UL for Mo is 8-11 mg, we have a margin to go forwards.
So then? I’m not shooting onto the crowd. I draw attention to the fact that some people could lack tone and / or poison themselves in certain circumstances. I wanted to take stock on the situation after reading an article by Chris Masterjohn, who tends to point out an extreme case in order to dismantle a deleterious mechanism. Better to be warned before, especially by people who eat little meat, have their period, and eat a lot of legumes, nuts and drink tea, mate or hibiscus herbal tea.
Sources and References on next post.

Sources and References
1) Excess manganese causes mitochondrial dysfunction by inhibiting CoQ10 synthesis.
Chris Masterjohn
2) 2 mg manganese is often mentioned as the safe upper limit of manganese consumption by the European Food Safety Authority. Rather a High RDA.
3) Scientific opinion on the tolerable upper intake level for manganese
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Dec 08 2023. EFSA Panel on Nutrition
When in excess, manganese has been reported to disrupt mitochondrial ATP production and induce oxidative stress (Gunter et al., 2012; Malecki, 2001; Zheng et al., 1998). Other proposed mechanisms include direct neuronal toxicity by the inhibition of mitochondrial respiration, leading to energy failure, impaired functions of glial cells (astrocytes and microglia), oxidative stress and excitotoxicity (Morcillo et al., 2021; Nyarko-Danquah et al., 2020).
& 3.3.1 Sources of dietary manganese.
Manganese is naturally present in a wide variety of plant-based products (Annex [Vous devez être inscrit et connecté pour voir ce lien]). High concentrations (up to 5000 μg/100 g) are found in nuts, tea leaves, legumes, grains and some fruits such as pineapples, banana and berries, while lower concentrations (< 400 μg/100 g) are found in most fruits and vegetables. Milk products, meat (except offals), fish and eggs have a relatively low content of manganese (< 100 μg/100 g). Whole grains contain more manganese than polished grains as most of it is in the bran. A cup of tea (200 mL) may contain 300–1000 μg manganese (Hope et al., [Vous devez être inscrit et connecté pour voir ce lien]). Other herbal infusions, such as maté and hibiscus infusions, also contain substantial amounts of manganese (> 500 μg/100 mL).
& 3.3.2.2 Main food contributors
The main food groups contributing to background manganese intake were grains and grain-based products (mainly bread and similar products and breakfast cereals), tea beverages and fruits (with highest contribution from banana) in all age groups, except for infants and toddlers, where instead of the tea beverages foods for the young populations (mostly cereal-based products) were important contributors (Annex [Vous devez être inscrit et connecté pour voir ce lien]).
In the one dietary survey on vegetarians from Romania, grain and grain-based products remain the main contributor to total manganese intake, followed by legumes (especially pulses) (Annex [Vous devez être inscrit et connecté pour voir ce lien]).
4) CoQ10 as membrane stabilizer
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5) Normal levels of Mo
DOI: [Vous devez être inscrit et connecté pour voir ce lien]  Association between urinary manganese and blood pressure. 2017
DOI: [Vous devez être inscrit et connecté pour voir ce lien]  Manganese-driven CoQ deficiency. 2022
*) RDA 1.3 mg; UL intake is 11 mg.
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*) Tolerable upper intake form minerals and vitamins. EFSA
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[Vous devez être inscrit et connecté pour voir ce lien]  (2022)
A safe level of intake of 8 mg/day was established for adults ≥ 18 years.
*) Nutrient interactions
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An individual's iron status can affect manganese bioavailability. Intestinal absorption of manganese is increased during iron deficiency and decreased when iron stores are elevated (i.e., high ferritin concentrations) [Vous devez être inscrit et connecté pour voir ce lien]. 
Supplemental magnesium (200 mg/day) has been shown to slightly decrease manganese bioavailability in healthy adults, either by decreasing manganese absorption or by increasing its excretion [Vous devez être inscrit et connecté pour voir ce lien].
*) Superoxide dismutase (SOD2), a mitochondrial enzyme, is also known as manganese-dependent superoxide dismutase (MnSOD),
MnSOD in Oxidative Stress Response-Potential Regulation via Mitochondrial Protein Influx doi: [Vous devez être inscrit et connecté pour voir ce lien] 2014.
The mitochondrial antioxidant manganese superoxide dismutase (MnSOD) is encoded by genomic DNA and its dismutase function is fully activated in the mitochondria to detoxify free radical O₂^•− generated by mitochondrial respiration. 
This antioxidant enzyme maintains cellular redox homeostasis. MnSOD is the key enzyme that protects the energy-generating mitochondria from oxidative damage. Levels of MnSOD are reduced in many diseases, including cancer, neurodegenerative diseases, and psoriasis.
*) Manganese Superoxide Dismutase: Guardian of the Powerhouse
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Factors that affect the expression and/or the activity of MnSOD, resulting in diminished antioxidant capacity of the cell, can have extraordinary consequences on the overall health of the cell by altering mitochondrial metabolic function, leading to the development and progression of numerous diseases.
*) Manganese toxicity
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*) Bacterial Infection
Invading microbes can use Mn to resist host immune responses. In fact, Mn uptake is essential for the virulence or harmfulness of many bacteria [[Vous devez être inscrit et connecté pour voir ce lien], [Vous devez être inscrit et connecté pour voir ce lien]].
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Excess manganese triggers the release of several inflammatory molecules (including TNF-α, IL-6, IL-1β, prostaglandins, and nitric oxide). It also activates the body’s key inflammatory signal, NF-κB. Altogether, this can cause inflammation in the brain and body [[Vous devez être inscrit et connecté pour voir ce lien], [Vous devez être inscrit et connecté pour voir ce lien], [Vous devez être inscrit et connecté pour voir ce lien]].
In a study of 633 people, those eating high-manganese diets had raised inflammatory markers (about 50% higher IL-1b and IL-6, 32% higher IL-8, and a more active NF-κB) [[Vous devez être inscrit et connecté pour voir ce lien]].

High dose manganese in food : Moderation with blue color:
chanvre / hemp. épinard / spinach. Tomato. ananas / pineapple. Tea 
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Comment: No problemo if you eat blue food once but don't cumulate 3 times high manganese > 1 in a day, several days, without taking CoQ10

Sulfite connection
CoQ10 is needed to clear hydrogen sulfide (H2S).
Sulfites (SO3) are found nearly everywhere as food additive. A 70 kg person can ingest 4 mg of sulfites maximum on daily base. Let’s suppose he / she eats 50 grams of dried fruit, followed by 100 grams of shrimp, then he drinks two glasses of white wine, it will quickly reach the fixed limit. (1-2)
Animal tests have revealed that sulfites cause thiamine deficiency (vitamin B1). (3) Their use is therefore not recommended because sulfites degrade thiamine, and could alter folic acid (B9) (4)
When Co-Q10 clears hydrogen sulfide, it takes electrons away. And in the process, glutathione is used up. If we lack Co-Q10, glutathione will be used up too. But we need glutathione to detox elsewhere.
            Health authorities have defined the tolerance threshold at 45 mg sulfite per day for a person of 60 kg. But some people will have to learn to manage their tolerance threshold from 1 to 10 mg per day ... (5)
Co-Q10 will be required to neutralize excess manganese
If we have manganese overload, Co-Q10 will be required too. Overexposure to manganese from foodstuff disrupts cellular energy metabolism. Excess cellular manganese selectively disrupts Co-Q10 biosynthesis, resulting in failure of mitochondrial bioenergetics. (6-7)
If you’re missing Co-Q10 because of manganese overload (8 – 12 mg), that means more hydrogen sulfide, sulfite, and S-sulfocysteine.
So, we shouldn’t lack C0-Q10 to avoid manganese toxicity (UL for Mo is 8 – 11 mg) and to manage sulfites. ( 7 - 8 )


Sources and References
1) Sulfites dans le vin
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2)  Fibromyalgie et la sulfite connexion
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2. [Vous devez être inscrit et connecté pour voir ce lien] (commentaires)
3. thiamine-and-food-additives (lien mort)
4. Dean D. Metcalfe, Ronald A. Simon, Food allergy: adverse reactions to food and food additives, Wiley-Blackwell 2003..
5. [Vous devez être inscrit et connecté pour voir ce lien]
6. Chris Masterjohn: “Iron Overload: Forget What You Thought You Knew”
Manganese overload causes headaches, irritability, insomnia, depression, and eventually loss of balance, problems walking normally, and Parkinson signs such as rigidity and tremor.
7. Chris Masterjohn: “Manganese inhibits CoQ10 so that mitochondrial respiration fails”
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8. Taurine could help
Taurine suppresses the trans-sulfuration pathway. This will prevent the overproduction of cysteine, and thus the overproduction of hydrogen sulfide and sulfite. In mice taurine reverses the mitochondrial damage with sulfites.
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