Supplemental free antioxidants are worse than useless

Many illnesses, such as schizophrenia, Alzheimer’s disease, Parkinson’s disease and bipolar disorder are associated with oxidant stress. Yet, increasing levels of free antioxidants by supplementing with more than RDA amounts of vitamin E, beta-carotene and vitamin C does not treat these illnesses.

Increasing levels of free antioxidants via supplmentation could be mucb worse than useless. Before iron can be absorbed iron must be reduced from Fe3+ to Fe2+. Antioxidants like vitamin C, vitamin E , beta-carotene and quercetin could one way or other promote the reduction of Fe3+ to Fe2+ in the gastrointestinal tract which would increase absorption. The goal, however, is to delay iron absorption as long as feasible.

An oxidant environment in the gastrointestinal tract is called for. Rather than taking iron with antioxidants iron would be taken with as much as feasible polypenol free fatty acids such as lignan free flax seed oil which would generate free radicals in the gastrointestinal tract. Supplementing with free antioxidants could be associated with very subtle but serious mineral dysregulations which would bascially be undiagnosable.

There is oxidant stress in lots of illnesses but this could be due to dysregulation of selenoproteins and dysregulation of iron metabolism which are not fixed by increasing levels of free antioxidants with supplemental vitamin C, vitamin E , beta-carotene and quercetin.

Iron defciency and negative sypmtoms in schizophrenia

Latent Iron Deficiency as a Marker of Negative Symptoms in Patients with First-Episode Schizophrenia Spectrum Disorder

by Sung-Wan Kim 1,2,*, Robert Stewart 3,4, Woo-Young Park 2, Min Jhon 1,2, Ju-Yeon Lee 1,2, Seon-Young Kim 1, Jae-Min Kim 1, Paul Amminger 5, Young-Chul Chung 6 and Jin-Sang Yoon 1,*


Iron deficiency may alter dopaminergic transmission in the brain. This study investigated whether iron metabolism is associated with negative symptoms in patients with first-episode psychosis. The study enrolled 121 patients with first-episode schizophrenia spectrum disorder, whose duration of treatment was 2 months or less. Negative symptoms were measured using the Positive and Negative Syndrome Scale (PANSS) and Clinician-Rated Dimensions of Psychosis Symptom Severity (Dimensional) scale of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). Prominent negative symptoms were defined as moderate or severe negative symptoms on the Dimensional scale of the DSM-5. Iron deficiency was defined as a serum ferritin ≤ 20 ng/mL. Patients with iron deficiency were significantly more likely to have prominent negative symptoms (45.2 vs. 22.2%; p = 0.014) and a higher PANSS negative symptoms score (p = 0.046) than those with normal ferritin levels. Patients with prominent negative symptoms had significantly lower ferritin levels (p = 0.025). The significance of these results remained after controlling for the duration of illness and other confounding variables. Our finding of an independent association between iron deficiency and negative symptoms in patients at the very early stage of illness implies that iron dysregulation has an effect on negative symptoms in patients with schizophrenia. The possibility of therapeutic intervention with iron should be further investigated.

I have been argunig in this blog that there are high IRP1 levels in schizophrenia due to difficulties in iron-sulfur cluster formation whereby cytosolic aconitase switches to IRP1. As ferritin mRNA has an iron response in the 5′ untranslated region high levels of IRP1 will decrease ferritin levels.

The most attractive supplements can be the most dangerous supplements

In terms of alternative and complimentary medicine 5-MTHF, alpha lipoic acid, folate and N acetyl cysteine are mainline treatments for depression.

There are lots of grounds to think these supplements could be very unsafe. Lipoic acid shares the same transporter with biotin and pantothentic acid. Lipoate inhibits the transport of pantothenic acid and biotin. The body uses miniscule quantities of biotin. 300 milligrams of lipoic acid twice a day could have a large negative affect on biotin transport. Lipoic acid does not work in bipolar depression which is not suprising, See the page on Bipolar Depression.

N-acetyl cysteine is associated with musculoskeletal adverse side effects. These musculoskeletal adverse side effects are almost totally impossible to get rid of and can be horrendous. Clincal trials are usually about 6 weeks long but musculoskeletal effects accumulate over time and can persist long after N-acetyl cysteine is stopped.

There are no grounds whatsover to hold than S-adenosyl methionine taken long term would not affect DNA methylation and histone methylation. Abberrant DNA methylation is associated with cancer, aging and mental illnesses. Minimally an explantion as to why greatly increasing S-adenosyl-l-methionine levels does not affect DNA and histone methylation long term has to be given but no explanatiton is provided.

5-methyltetrahydrofolate inhibts glycine-N-methyltransferase which degrades S-adenosyl methionine. With 5-methyltetrahydrofolate supplementation S-adenosyl methionine levels would again be expected to greatly increase with again unknown consequences to DNA methylation and histone methylation. No consequences would be very surprising. Despite great early enthusiasm folic acid supplementation has been a bust in the prevention of a range of illnesses associated with high homocysteine levels.

What is it about these supplements that makes them so attractive? One very definitely notices these supplements when one takes them.

Why are supplements frequently effective placebos?

First of all I clearly do not think all supplements are placebos but frequently responses to supplements are placebo responses. A fact about supplements is that when supplements are taken there are very frequently noticable effects. When ill, change is viewed as a positive and the perception, which can be an illusion, is that one is moving away from being ill hence a placebo response.

The difficulty with supplements as placebos is that frequently change is not for the better or even biologically neutral and can even be for the worse which I think is all too frequently the case with supplements. Supplements are a minefield.

Individuals are biolgcially programmed to try to improve their health. Most people have a strategy for staying healthy. A non fad diet, excercise, and a continous learning program are right now by far the safest way to go. The best way to get a placebo response now from supplements is to take only one or two supplements and take only dosages suggested on bottles. This sounds facetious but is not taking a supplement at the suggested dosage that is ‘good for the immune system’ or ‘good for cardiovascular health’ is the safest way to get a placebo response though herbs must be avoided. All sorts of junk is put into herb formulations. I think one day supplements can be a key part of a healthy way of living.

That Silicon Valley is full of individuals who take lots of nootropics and lots of supplements does not bode well for Silicon Valley’s future.

Selenium and osteoporosis

Selenium intake in a dose-response manner is negatively correlated with osteoporosis. Compared with the lowest quartile tho odds ratios of osteoporosis were 0.72, 0.72 and 0.47 for the second, third and fourth quartiles of dietary Se intake, respectively. See also this paper.

In my paper on osteoporosis on the Osteoporsis page I argue that the transsulfuration pathway is dysregulated in osteoporosis. Dysregulation of the transsulfuration pathway would dysregulate selenium metabolsim as the food form of selenium, selenomethionine is metabolized via the transsulfuration pathway. Se-methylselenocysteine can be metabolized by kynurenine aminotransferase whereby Se-Methyl-L-selenocysteine + H2O <=> Pyruvate + Ammonia + Methaneselenol.Kynurenine aminotransferase is an enzyme that is not in the transsuluration pathway whereby Se-methylselenocysteine is the prefecred form of supplemental selenium as selenium from Se-methylselenocysteine is biovailable. Dosages of Se-methylselenocysteine should not exceed 200 micrograms a day. More is not better.

Schizophrenia and n-6 and n-3 fatty acids

In patients with schizophrenia, there are substantial depletions of both n-6 and n-3 fatty acids in red cell membranes . Alpha-linolenic acid (an n-3 fatty acid) and linoleic acid (a n-6 fatty acid) are essential fatty acids that must be obtained from the diet. Taurine is required for formation of various bile acids. Bile acids are needed for fat absorption. Decreased levels of taurine could lead to decreased absorption of both alpha-linolenic acid and linoleic acid from which many other n-6 and n-3 fatty acids are synthesized. Low levels of taurine in schizophrenia could explain both decreases in n-6 and n-3 fatty acids seen in schizophrenia. In schizophrenia supplmenting with some combination of alpha-linolenic acid and linoleic acid could be better than supplmenting with either alone.

Taurine chloramine downregulates the production of proinflammatory mediators

Taurine chloramine produced from taurine under inflammation provides anti-inflamnatory and cytoprotective effects

Chaekyun Kim  1 Young-Nam Cha


Taurine is one of the most abundant non-essential amino acid in mammals and has many physiological functions in the nervous, cardiovascular, renal, endocrine, and immune systems. Upon inflammation, taurine undergoes halogenation in phagocytes and is converted to taurine chloramine (TauCl) and taurine bromamine. In the activated neutrophils, TauCl is produced by reaction with hypochlorite (HOCl) generated by the halide-dependent myeloperoxidase system. TauCl is released from activated neutrophils following their apoptosis and inhibits the production of inflammatory mediators such as, superoxide anion, nitric oxide, tumor necrosis factor-α, interleukins, and prostaglandins in inflammatory cells at inflammatory tissues. Furthermore, TauCl increases the expressions of antioxidant proteins, such as heme oxygenase 1, peroxiredoxin, thioredoxin, glutathione peroxidase, and catalase in macrophages. Thus, a central role of TauCl produced by activated neutrophils is to trigger the resolution of inflammation and protect macrophages and surrounding tissues from being damaged by cytotoxic reactive oxygen metabolites overproduced during inflammation. This is achieved by attenuating further production of proinflammatory cytokines and reactive oxygen metabolites and also by increasing the levels of antioxidant proteins that are able to scavenge and diminish the production of cytotoxic oxygen metabolites. These findings suggest that TauCl released from activated neutrophils may be involved in the recovery processes of cells affected by inflammatory oxidative stresses and thus TauCl could be used as a potential physiological agent to control pathogenic symptoms of chronic inflammatory diseases.

Taking supplemental taurine lowers blood pressure in humans

Taurine lowers blood pressure in humans by increasing synthesis of hydrogen sulfide, which is a vasodilator, through increasing activities of cystathionine beta-synthase and cystathionine gamma-lyase, the two enzymes in the transsulfuration pathway. Cystathionine beta-synthase and cystathionine gamma-lyase synthesize hydrogen sulfide. A meta-analysis indicates that taurine lowers blood pressure in clinically relevant amounts. Taurine also decreases homocysteine levels in humans. There is also lots of evidence from animals than taurine lowers total cholesterol. Research points to taurine as being the factor for Japanese longevity which could be due to taurine lowering various cardiovascular risk factors. The actions of taurine are more pronounced when taurine is taken on an empty stomach.

For the experimentally inclined

Calcium citrate contains a whole lot of citrate. The formula of calcium citrate is Ca3(C6H5O7)2. Calcium citrate is about 85% citrate. Citric acid can be purchased on Amazon. 4 ounces of food grade citric acid can be purchased on Amazon for $4.99. 4 ounces should be more than enough for the experiment. 600 millgrams of calcium from calcium citrate would have 4000 milligrams of citrate.

A citric acid drink with say 4000 milligrams of citric acid could be drunk 3 or 4 times a day for 3 or 4 days. The drink would only contain water and citric acid. The hypothesis being tested is whether citric acid can befuddle thinking. I am not actually recommending anyone do this experiment but as I stated for the experimentally inclined.

Citric acid should increase iron absorption still I think the adverse effects of citric acid are due to an iron interaction with citric acid in the gut which makes iron unavailable in the gut with very significant negative effects. Iron chelated to citric acid in the gut is not bioavailable in the gut. Iron must be available in the gut as well as systematically. Enhancers of iron absorption can have negative effects on iron metabolism in the gut.

In defense of a calcium citrate calcium supplement but not Mountain Dew the citrate in calcium citrate could largely be be chelated to calcium rather than to iron.

How are Mountain Dew focus groups actually run? Do individuals running the focus groups give indivduals in the focus groups Mountain Dew to drink then riff in ads on postive reactions to Mountain Dew and the individuals who gave those postive reactions?

Calcium homeostasis in osteoblasts and osteoclasts and bone formation and bone resorption

Osteoblasts are involved in bone formation. Osteoclasts break down bone. Dysregulation of calcium homeostasis in osteoblasts and osteoclasts could lead to bone abnormalities. In the forward mode of the Na/calium exchanger calcium is effluxed from cells while in reverse mode there is an influx of calcium into cells via the Na/calcium exchanger.

Taurine inhibits the reverse mode of the Na/calcium exchanger. The Na/calcium exchanger (NCX) is expressed in osteoblasts. The taurine transporter is expressed in osteoblasts. In osteoblasts inhibting the reverse mode of the Na/calcium exchanger would increase calcium net efflux from osteoblasts which would increase bone formation. Taurine inhibits osteoclastogenesis through the taurine transporter. In osteoclasts inhibiting the reveres mode of the Na/calicum exchanger would inhibit the influx of calcium into osteoclasts from bone which would inhibit bone resorption.

Extracellular calcium levels are very tightly controlled and are very, very frequently tested. However intracellular homeostasis of calcium in osteoblasts and osteoclasts could be very imporant as to whethere there is bone bone growth or bone resorption. Taurine is involved in calcium homeostasis in cells. Taurine both increases bone growth and inhibits bone resorption. The positive effects of taurine on bone fomation could be via the inhibition of the reverse mode of the Na/calcium exchanger in osteoblasts and osteoclasts.