No Researcher Knows So Much About Iodine And Human Evolution As The Italian Dr Sebastiano Venturi

[LeeLemonoil]

https://www.researchgate.net/public...tion_by_Sebastiano_Venturi_and_Michel_E_Begin

ntroduction Evolution of the hominin lineage is marked by progressive brain expansion and complexity concomitant with coordinated changes in other morphological and behavioral traits that characterize speciation events. In addition to gene variation, changes in climate, habitat, and diet are well-recognized environmental stimuli for evolutionary change. Iodine is an environmental stimulus to which living organisms react, a point particularly evident in amphibian metamorphosis and potentially also in hominin evolution. In toto, selection pressures effecting evolutionary change involve biological mechanisms permitting adaptation and evolution under changing environmental conditions. A common biological control mechanism could potentially coordinate a suite of physiological, morphological, and behavioral changes as important as brain evolution. We contend here that such a mechanism was hormonal and that thyroid hormone and iodine were pivotal components of such a mechanism. The principal fossil sites of hominins correlated in space and time with volcanic and fissural local or nearby iodine sources (Borensztejn, 2005). In vertebrates, iodine is incorporated into thyroid hormone in the thyroid gland. Crockford (2003, 2008) provided solid evidence that changing thyroid function, specifically rhythms of thyroid hormone secretion, is crucial for speciation events taking place over decades. The same thyroid hormone mechanism can be applied to the process of humanizing australopithecines. Here, we postulate a link between thyroid function, iodine, and evolutionary changes as they apply to the evolution of hominins and, more specifically, the large brain of Homo sapiens. We emphasize changes in habitat and the connection between enhanced dietary availability of iodine, selenium, and polyunsaturated fatty acids as brain-selective nutrients necessary for thyroid function and hominin brain expansion.

https://www.researchgate.net/public...205_2014_Part_2_S_Venturi_M_Venturi_2014_LINK

The structural, metabolic and synergic actions of iodine and polyunsaturated fatty acids (PUFAs) in life evolution and in the ‘membrane lipid language’ of cells are reviewed. Iodine is one of the most electron-rich atoms in the diet of marine and terrestrial organisms and, as iodide (I-), acts as an ancestral electron-donor through peroxidase enzymes. It is the most primitive inorganic antioxidant in all iodide-concentrating cells, from primitive marine algae to more recent vertebrates. About 500 million years ago, the thyroid cells originated from the primitive gut of vertebrates, then migrated and specialized in the uptake and storage of iodocompounds in the thyroid, a new follicular organ. In parallel, ectodermic cells, differentiated into neuronal cells, became the primitive nervous system and brain. Both these cells synthesized iodolipids, as novel ‘words’ of the chemical ‘lipid language’ devoloped among cell membranes during the evolution of life, for better adaptation to terrestrial environments. The study of iodolipids is a new area of investigation, which might be useful for research on apoptosis, carcinogenesis and degenerative diseases, as well as for trying to understand some problems discussed regarding human evolution.

 

[LeeLemonoil]

Evolutionary roots of iodine and thyroid hormones in cell–cell signaling

In vertebrates, thyroid hormones (THs, thyroxine, and triiodothyronine) are critical cell signaling molecules. THs regulate and coordinate physiology within and between cells, tissues, and whole organisms, in addition to controlling embryonic growth and development, via dose-dependent regulatory effects on essential genes. While invertebrates and plants do not have thyroid glands, many utilize THs for development, while others store iodine as TH derivatives or TH precursor molecules (iodotyrosines)—or produce similar hormones that act in analogous ways. Such common developmental roles for iodotyrosines across kingdoms suggest that a common endocrine signaling mechanism may account for coordinated evolutionary change in all multi-cellular organisms. Here, I expand my earlier hypothesis for the role of THs in vertebrate evolution by proposing a critical evolutionary role for iodine, the essential ingredient in all iodotyrosines and THs. Iodine is known to be crucial for life in many unicellular organisms (including evolutionarily ancient cyanobacteria), in part, because it acts as a powerful antioxidant. I propose that during the last 3–4 billion years, the ease with which various iodine species become volatile, react with simple organic compounds, and catalyze biochemical reactions explains why iodine became an essential constituent of life and the Earth's atmosphere—and a potential marker for the origins of life. From an initial role as membrane antioxidant and biochemical catalyst, spontaneous coupling of iodine with tyrosine appears to have created a versatile, highly reactive and mobile molecule, which over time became integrated into the machinery of energy production, gene function, and DNA replication in mitochondria. Iodotyrosines later coupled together to form THs, the ubiquitous cell-signaling molecules used by all vertebrates. Thus, due to their evolutionary history, THs, and their derivative and precursors molecules not only became essential for communicating within and between cells, tissues and organs, and for coordinating development and whole-body physiology in vertebrates, but they can also be shared between organisms from different kingdoms.

 

[LeeLemonoil]

https://www.researchgate.net/public...ent_and_action_of_human_extrathyroidal_iodine

3CONTROVERSY IN THE CONTENT AND ACTION OF HUMAN EXTRATHYROIDAL IODINE
1
FIGURES
Fig. 1.
Iodine in Evolution
Over three billion years ago in the primitive sea, blue-green algae were the first living Prokaryota to
produce oxygen and halocarbons (such as CH3I) in the atmosphere, and also PUFAs in lipid membranes of
marine organisms. About 500 million years ago (Mya), when the primitive brain also evolved in marine
animals, thyroid cells originated from the primitive fore-gut in vertebrates, migrated and specialized in
uptake and storage of iodocompounds in a novel follicular “thyroidal” structure, as a reservoir for
iodine. 350 Mya, some vertebrates evolved into amphibians and reptiles when they colonized the
iodine deficient land. The new hormonal action of T3 was made possible by the formation of nuclear T3-
receptors in the cells of vertebrates. Firstly, about 500 Mya, in primitive Chordata appeared alfa-T3-
receptors with a metamorphosing action, and then, about 200 Mya, in t he birds and mammals appeared
beta-T3-receptors with metabolic and thermogenetic actions. (Venturi, 2000)
Fig. 1.
Iodine in Evolution.
Over three billion years ago in the primitive sea, blue-green algae were the rst living Pro-
karyota to produce oxygen and halocarbons (such as CH3I) in the atmosphere, and also PU-
FAs in lipid membranes of marine organisms. About 500 million years ago (Mya), when the
primitive brain also evolved in marine animals, thyroid cells originated from the primitive
fore-gut in vertebrates, migrated and specialized in uptake and storage of iodocompounds in
a novel follicular “thyroidal” structure, as a reservoir for iodine. 350 Mya, some vertebrates
evolved into amphibians and reptiles when they colonized the iodine decient land. The new
hormonal action of T3 was made possible by the formation of nuclear T3-receptors in the
cells of vertebrates. Firstly, about 500 Mya, in primitive Chordata appeared alfa-T3-receptors
with a metamorphosing action, and then, about 200 Mya, in t he birds and mammals appeared
beta-T3-receptors with metabolic and thermogenetic actions



n the cells, iodide acts as an electron donor in the presence of H2O2 and per-
oxidases. The remaining iodine atom readily iodinates tyrosine, histidine and unsatu-
rated lipids, and thus neutralizes its own oxidant power (Table A & Table B). The
membrane metabolites of PUFAs have an essential role in intercellular biochemical
communications. Venturi has suggested that iodine (and selenium) played an impor-
tant role in protecting fragile, polyunsaturated membrane lipids, proteins and DNA
from oxidation, and for this reason, these elements are important in animal develop-
ment and in human brain evolution [ 17-19, 29, 30 ] . In fact, iodide is a mild reduc-
ing agent, which is a chemical term for an antioxidant. Its antioxidant properties can
be expressed quantitatively as a redox potential

1
Table. A. Proposed antioxidant biochemical mechanism of iodides.
2I- + Peroxidase + H2O2 + 2 Tyrosine → 2 Iodo-Tyrosine + H2O+ 2 e- (antioxi-
dants); 2 e- + H2O2 + 2 H+
(of intracellular water-solution) → 2 H2O
Table. B. Proposed antioxidant biochemical mechanism of iodides, probably the most an-
cient mechanisms of defence from poisonous reactive oxygen species.
2 I- + Peroxidase + H2O2 + Tyrosine, Histidine, Lipids, Carbons → → Iodo-Com-
pounds + H2O + 2 e- (antioxidants) Iodocompounds: Iodo-Tyrosine, Iodo-Histidine,
Iodo-Lipids, Iodo-Carbons
Cunnane [31, 32] and Crawford (2010) [33, 34] in the chapter “Long-chain pol-
yunsaturated fatty acids (PUFAs) in human brain evolution” reported, with regard
to the ‘language of lipids,’ that the importance of the increased complexity of these
lipids was brought about by aerobic metabolism: whereby the simple language of
prokaryotes, with only a few words, was developed into a vocabulary of over 1,000
words, in eukaryote cells. Thomasz et al., [35, 36], Dugrillon [37], Aceves et al., [38,
39] and Venturi [40, 41] recently reported that not only thyroid but also nervous and
breast cells synthesized iodolipids, as novel ‘words’ of this biochemical language
developed among cell membranes during the evolution of life. I-concentrating ecto-
dermic cells, differentiated into neuronal cells, became the primitive nervous system
capable, as thyroid cells, of synthesizing iodolipids.
In the sea, algal phytoplankton, the basis of the marine food chain, acts as a bio-
logical accumulator of iodides, selenium and polyunsaturated fatty acids (PUFAs).
Iodine protects the fragile PUFAs of cellular membranes in primitive algae from
lipid peroxidation, and for the same reason, it is important in human brain evolution.
In fact, in chemical terms, is called ‘iodine value’ or ‘iodine number’ the determina-
tion the amount of unsaturation in PUFAs by iodine reaction [42] . This unsaturation
is in the form of double bonds react with I-compounds [17]. Some iodolipids have
been shown to regulate cellular metabolism and several authors have also reported
their effects on growth inhibition and apoptosis in some tumoral cells In PUFAs the
presence of a double bond between two carbons provides them with the possibility
of changing their molecular structure through enzymes such as phospholipases, cy-
clooxygenases and lipoxygenases [

 

[LeeLemonoil]

Venturi is an enthusiast researcher with his own hypothesises and on his own too.

Since his stuff touches so many of our fundamental topics here ... T3, PUFA and Evolution and he has that rouge charme, it would be nice to have Dr. Peat have a glance at these publications

 

[LLight]

The LXR transcription factor activation seems to be able to upregulate the NIS (sodium/iodide symporter):
The cholesterol-derived metabolite dendrogenin A functionally reprograms breast adenocarcinoma and undifferentiated thyroid cancer cells - PubMed
"131-I incorporation in the 8505c cells was stimulated by DDA as well as by the synthetic LXR ligand, GW3965. Together these data show that the re-differentiation of breast and thyroid cancer cells by DDA, is associated with the recovery of functional NIS expression and involves an LXR-dependent mechanism."

Moreover, the LXR and thyroid hormone receptors could features some interactions:
Regulation of thyroid hormone activation via the liver X-receptor/retinoid X-receptor pathway

"Our data indicate that hDIO2 transcription is negatively regulated by both 22(R)-OH-cholesterol and 9-cis RA, which is consistent with LXR/RXR involvement. In vivo, the inhibition of D2-mediated tri-iodothyronine (T3) production by cholesterol/9-cis RA could function as a feedback loop, given that T3 decreases hepatic cholesterol levels."​

Is iodine the important part of thyroid hormone? Is T3 decrease because of LXR activation "unimportant"?

 

[LLight]

Lugol Increases Lipolysis through Upregulation of PPAR-Gamma and Downregulation of C/EBP-Alpha in Mature 3T3-L1 Adipocytes

Abstract
"Overweight and obesity are defined as excessive and abnormal fat accumulation that is harmful to health. This study analyzes the effect of different concentrations of the lugol solution (molecular iodine dissolved in potassium iodide) on lipolysis in cultured 3T3-L1-differentiated adipocytes. The mature adipocytes were treated with doses from 1 to 100 µm of lugol for 0.5, 6, and 24 h. The results showed that mature adipocytes exposed to lugol decrease their viability and increase caspase-3 activity with a lethal dose (LD50) of 473 µm. In mature adipocytes, lugol decreased the total intracellular lipid content, being significant at doses of 10 and 100 µm after 6 and 24 h of treatment (P < 0.01), and the accumulation of intracellular triglycerides decreased after 24 h of exposure to lugol (P < 0.05). Lugol treatment significantly increases the release of glycerol to the culture medium (P < 0.05). The levels of adipocyte-specific transcription factors C/EBP-α were downregulated and PPAR-γ upregulated after 30 min with lugol. These results indicate a lipolytic effect of lugol dependent on PPAR-γ and C/EBP-α expression in mature 3T3-L1 adipocytes."

Discussion
"This study evaluated the ability of iodine to directly induce lipolysis in mature 3T31-L1 adipocytes. It has been previously reported that iodine uptake requires NIS and PEN transporters [28]. In this regard, previous studies have reported that adipose tissue expresses the iodine transporter NIS [23], which is in agreement with our results where we show that only mature adipocytes express the two mRNA of NIS and PEN transporters. This study shows that expression of NIS and PEN is regulated by transcription factors involved in adipocyte differentiation, such as the SREBP transcription factor [29, 30]. Transcriptional upregulation of the NIS gene by SREBP could be mediated by a functional binding site located in the NIS 5′-flanking region, which is not necessary for TSH-dependent NIS gene regulation. This indicates that regulation of the NIS gene by SREBP is important in extra thyroidal tissues that accumulate iodine and are not regulated by TSH [6]."

"Thus, iodine nutrition alterations may be involved in the pathogenesis of obesity, suggesting that iodine is important on the maintenance of proliferation/lipolysis balance in adipose tissue. However, more research is required in order to know the exact mechanism of action of iodine in adipocytes."​

SREBP increases the expression of the sodium/iodide symporter NIS. The LXR is known to activate SREBP.
Adipocytes need iodine too.

 

[LLight]

Iodine, a preventive and curative agent in the COVID-19 pandemic?

"It has been known for a long time that iodine has unique germicide properties [1]. During the Asian flu in 1957 it was reported that the use of Mandl’s paint seemed to prevent the development of influenza. In the untreated group 14% developed influenza, this against 2.8% in the treated group. Furthermore, in already developed influenza, starting iodine after three days of illness reduced the number of cases significantly compared to the control group, the effect being clear after only two days of treatment [2].

Pathophysiological research shows that iodine could support the innate immune system in fighting both bacterial and viral infections [3], [4], [5]. In 2013 it was shown in newborn lambs inoculated with respiratory syncytial virus (RSV) that iodine treatment resulted in less lung lesions and less pulmonary expression of RSV antigen. Also, in 3-week-old lambs it was demonstrated that iodine supplementation reduced the severity of RSV-infection [3]. Finally, epidemiological data show that in the current COVID-19 pandemic the Japanese, known for their high iodine intake, have a very low number of COVID-19 deaths compared to other countries, despite the fact that Japan has the eldest population of the world and the national lockdown has thus far been one of mild measures [6], [7].

Taken into account the above mentioned pathophysiological, clinical and epidemiological data, we hypothesize that iodine is a crucial element in the optimal functioning of the innate immune system and could be the magic bullet for fighting the COVID-19 pandemic, in both a curative and preventive way. Prevention might be reached easily because of very limited side effects and fast uptake by oral supplementation. Besides it should be borne in mind that iodine deficiency is estimated to affect one third of the world population at the moment."​

 

[LLight]

Sterol regulatory element-binding proteins are regulators of the NIS gene in thyroid cells - PubMed

"In conclusion, the present study shows, for the first time, that the sterol-sensitive SREBPs are not only functional in tissues with pronounced lipid biosynthesis activity, such as liver or adipose tissue, but also in thyroid epithelial cells. The observation from this study that SREBP-1c and SREBP-2 are novel transcriptional regulators of NIS, which is essential for thyroid hormone synthesis, indicates that SREBPs are possible novel targets for pharmacologic modulation of thyroid hormone synthesis and for induction of NIS for effective radioiodine therapy."
​

The LXR activates SREBP-1C which itself upregulates NIS in the thyroid. Maybe the LXR is not as opposed to the thyroid hormone effect after all.

Another "fun fact": the LXR could be involved somehow in Lupus, which is associated often with thyroiditis/Hashimoto.

 

[LeeLemonoil]

Shows again how efficient physiology is. Banal epithelial cell? Pfffhh. And bang. Involved in hormone synthesis too. It’s the freaking evolution. Only stuff that get things done efficiently went through.

LiverX, RetinoidX, FarnrsolX ... all intertwined, all crosscommunicating and interdependent. Their respective ligands thus modulating actions on all of them. The names, given when not much was known about them, are misleading in a way at this point

 

[LLight]

Shows again how efficient physiology is. Banal epithelial cell? Pfffhh. And bang. Involved in hormone synthesis too. It’s the freaking evolution. Only stuff that get things done efficiently went through.

LiverX, RetinoidX, FarnrsolX ... all intertwined, all crosscommunicating and interdependent. Their respective ligands thus modulating actions on all of them. The names, given when not much was known about them, are misleading in a way at this point

Thanks for your input, it was helpful to me.

Indeed, they are interdependent and even feature redundancy in their ligands & functions.

I think that this fact could help me resolve the contradiction I think I'm observing between the supposed almost always bad effect of the NFAT5/TonEBP (except the increased efficiency of the immune system and the osmolyte uptake) described in the scientific literature, and the benefits (some) people can get when they restrict their fluid consumption or when they dry fast (which supposedly activate NFAT5).

I think it's possible NFAT5 is not the only transcription factor able to sense osmolarity, directly or indirectly, and that the other supposed ones (LXR/FXR/TGR5) tend to carry more of the "good effects" (improved metabolism of bile acids and cholesterol, detoxification, lowered inflammation but improved immune response).

By analysing their effect independently, we can't have the full picture and possibly miss their combined impact:

1. Analysing NFAT5 function by subjecting a single cell to osmotic stress, while in vivo, the liver may have be producing oxysterols because of the dehydration stress, activating the inflammation-reducing effect of the LXR systemically, would be missing the whole effect.
2. Analysing the impact of NFAT5 on blood clotting (via vWF production) while not taking into account the inverse effect of the LXR on lowering blood coagulation may be misleading.

 

[Steven Bussinger]

Is iodine the important part of thyroid hormone?

Thyroid – Violien

Cells in the body convert T4 to T3 as needed. Selenium is needed for this conversion.
The thyroid makes mainly T4. T4 is a storage hormone. The body can tolerate relatively large fluctuations in T4 production and levels without you being aware of this. This way, if the thyroid gets sick temporarily (because of a bad flu for instance), your body can still get enough T3 and you’d be none the wiser.
Having a store of T4 floating around makes the system really stable. The store of T4 can be low or high, as long as there is enough to make enough T3, you as a person feel well and healthy. Only when stores get really low or really high do you start to feel off.
T3 on the other hand is regulated within a much tighter range. Low T3 makes you feel hypothyroid, cold and slow. High T3 makes you feel jittery with a rapid heart beat.

Really, really low iodine will trigger the body to lower the TSH. This results in favouring T3 production over T4 production (regardless of the amount of selenium you have, because this is a crisis situation). It is the low TSH that stimulates this switch from mainly T4 to mainly T3 production. The math behind this is simple: T3 takes one less iodine atom than T4 does, so in an way it’s cheaper. This way, a little iodine goes a long way.

 

[LLight]

Thyroid – Violien

Thanks.

Yes, it is rather obvious that iodine is the important part of thyroid hormones, otherwise these hormones (which could be any other molecule) wouldn't contain 4 or 3 atoms of iodine.

According to Sebastiano Venturi, iodide could be a powerful antioxidant.

If T4 is reduced to T3 directly in the cell (if I remember correctly, I think I read that it was a significant source of T3), it both brings an antioxidant (an iodide ion) and allows the oxidative metabolism to happen.

But what if iodine is brought into the cell not by T4 but by free iodine and symporter upregulation (while deiodinase is downregulated)? You would have iodide in the cell, but no signal to increase the metabolism? Maybe having an alternative source of iodine for the cell increases the T3 receptor sensitivity? That would explain the observations of Brownstein with his thyroid hormones-supplemented hypothyroids patients doing better with inorganic iodine. Is the LXR an important piece of the puzzle?

Maybe my understanding is too simple, or obvious, or blatantly wrong

 

[MitchMitchell]

I’ve been listening to Dr Rouzier who is fond of getting t3 above the “normal” range [2.0-4.5] because he says 20yo’s free t3 is ~7.0. So he prescribes at least 25mcg t3 to his patients and more if required. Wants to suppress the tsh.

I’m wondering if something like kelp or whatever supplement that’s safe and high in iodine would do the job: suppress tsh, keep free t3 (and t4) nice and high.

 

[LLight]

An ovni:

Etheric biology

Several observations made during the course of studies on stealth-adapted viruses are explainable by a pervasive, energy-rich, ether environment. Acti…

www.sciencedirect.com

Capturing etheric energy
The working model for how iodine is working is that it is facilitating the absorption of an external (etheric) energy.

 

[boris]

I’ve been listening to Dr Rouzier who is fond of getting t3 above the “normal” range [2.0-4.5] because he says 20yo’s free t3 is ~7.0. So he prescribes at least 25mcg t3 to his patients and more if required. Wants to suppress the tsh.

I’m wondering if something like kelp or whatever supplement that’s safe and high in iodine would do the job: suppress tsh, keep free t3 (and t4) nice and high.

Under 1mg of iodine should be safe to boost thyroid (I think it was said in a recent interview with Peat). High amounts will supress the thyroid.

 

[LeeLemonoil]

An ovni:

Etheric biology

Several observations made during the course of studies on stealth-adapted viruses are explainable by a pervasive, energy-rich, ether environment. Acti…

www.sciencedirect.com

Highly interesting. Maybe that’s why seaweed is high in iodine and why the ancestors of Mitos were iodine dependent

 

[Sitaruîm]

I'm fairly young, mid 20s, and my backyard was full of frogs in the summer. I had fun collecting as many as I could in a bucket, they were huge!

 

[MyUsernameHere]

Iodine sounds good to me on paper. It improves my sleep and skin quality, but by every other marker (TSH increasing, hair thinning, nail skin disconnecting and receding) I become more hypothyroid when I take Lugol's doses. Perplexing.

 

[Sitaruîm]

Iodine sounds good to me on paper. It improves my sleep and skin quality, but by every other marker (TSH increasing, hair thinning, nail skin disconnecting and receding) I become more hypothyroid when I take Lugol's doses. Perplexing.

How do you use iodine? I was thinking of using a tiny bit of Lugol's to brush my teeth as it is supposed to help with bleeding gums. Would you say that my body will assimilate non negligible amounts of it this way?

 

[TheSir]

Iodine sounds good to me on paper. It improves my sleep and skin quality, but by every other marker (TSH increasing, hair thinning, nail skin disconnecting and receding) I become more hypothyroid when I take Lugol's doses. Perplexing.

Perhaps it is revealing a pre-existing deficiency of one nutrient or another?