Dandruff or scalp irritation? Try BLOO.
More from them:
Now a serious metal band with fine artists:
)Glycolysis can be reversed starting from different molecules, and PC-derived oxaloacetate is one of the ways. Reverse glycolysis doesn't have to end on glucose (or glycogen) either, reversal can be partial to get to the branching points, as an alternative means to yield products needed for biosynthesis.
The issue relates to the carefree thiamin supplementation. Enthusiasts treat it as if it could only serve to disinhibit pyruvate dehydrogenase as intended, but it's not the case.
B Vitamins and Their Role in Immune Regulation and Cancer
TKT and KGDH can be overactive, whereas PDH underactive in cancer. Additional thiamin would be in favor of the ongoing activity of TKT and KGDH, while going against the inhibition of PDH.
For thiamin to get to mitochondria, it must first pass through the cytosol, where it's activated to thiamin diphosphate. Depending on the exact site of activation, TKT is cytosolic and may have privileged access to extra thiamin.
Linking vitamin B1 with cancer cell metabolism
If thiamin reaches mitochondria in therapeutic amounts, PDH must compete with KGDH for it, and PDH is more susceptible to regulation and inhibition than KGDH. Even with proper amounts of active thiamin, PDH may remain inhibited as a consequence of other controlling factors. And the TCA cycle (with KDGH) can be running independently of PDH. For example, with acetyl groups from fatty acids and ketoglutarate from glutamate.
Consider this:
"The thiamine concentration in plasma is observed to be in the range of 10-20nM. We used 10nM thiamine concentration as a control group to simulate the physiological levels of thiamine observed in human plasma."
Below is a projection relying on maximum plasma concentrations after each oral dose (thiamin HCl).
Pharmacokinetics of high-dose oral thiamine hydrochloride in healthy subjects
It's an optimistic curve. Suppose that rate keeps increasing and we reach a maximum concentration of 1200 nmol/L (0.0012 mmol/L or mM) with 3 g of oral thiamin (although the dose can get much higher without risk of toxicity). If you think that 3000 nM was an exaggerated level, the following experiment with cultured cells is often mentioned to defend supplementation:
High Dose Vitamin B1 Reduces Proliferation in Cancer Cell Lines Analogous to Dichloroacetate
At about 2 mM (2,000,000 nM) of the tested concentrations is where they started to observe a decrease in proliferation. The half-inhibition concentrations were 4.9 and 5.4 mM.
Yet, we have this experiment that's more encouraging:
The effect of thiamine supplementation on tumour proliferation: a metabolic control analysis study
The highest dose led to a 10% reduction in proliferation. The extrapolated dose may be something like 250 mg/person, but administration was subcutaneous.
⠀(from here)
In any case, for the overflow of thiamin to target PDH and make the effect prevail, the dose has to be extreme.
Considering the multiple influences on PDH, it remains possible that a major benefit of thiamin comes instead from its impact on carbonic anhydrases. Ray pointed out that it can work as an inhibitor and Jorge posted this experiment on the Antitoxin Forum:
It's feasible:
Fingers crossed that it applies to other carbonic anhydrase forms as well.
The Expression of Carbonic Anhydrases II, IX and XII in Brain Tumors
Despite carbonic anhydrases 9 and 12 being exposed on the surface of cells, the cells might be clustered in poorly vascularized tissues. If it's not a blood cancer, we can expect a sharp decrease in the thiamin concentration as we get to the core of this mass, which strengthens the idea that it's worth being extreme in supplementing it in cancer.
I think that the intention was to recreate the appearance of old paper. In this case, observe that the interior tends to be spared of degradation and the borders seem closer to Firefox's sepia than the artificial color in use:
Not even book antiquaries adopt it:
I agree that these aspects are secondary to content quality, but content quality is somewhat irrelevant to the discussion, and the post composer works independently from the result. The appearance for reading can be improved without interfering with that of writing.
These topics sound superficial, but I find interesting how details of a website affect its visitors. Since it's a health forum, with members possibly not functioning optimally, any tweak must count. They would be final adjustments relative to the early format. I'm reposting them here for Bradley to gauge preferences.
Regarding fonts, it's telling that avid book readers favor seriffed fonts almost unanimously, just as the majority of websites oriented towards literature (an everyday example would be Substack).
To reinforce, the bright side of biotin is unlikely to be in diverting pyruvate away from lactate when its oxidation is inhibited, but in helping to process this lactate once it's taken up by normal cells.
For an idea of the extent of lactate production:
Lactate Metabolism in Patients with Metastatic Colorectal Cancer
"Using an isotope tracer technique, we found increased rates of lactate production in 20 patients with metastatic colorectal cancer [Ca] compared to 13 control subjects [C] of comparable age and sex (15.6 ± 1.3 μmol/kg/min versus 10.4 ± 0.6 μmol/kg/min; p < 0.01)."
Their most extreme case produced lactate at 34.5 μmol/kg/min (3.48 mol/70 kg/24 h).
2 lactates per 1 glucose:
Unit conversion:
They discount the typical production based on the control group, which was 10.4 μmol/kg/min (1.05 mol/70 kg/24 h):
Unit conversion again:
The difference:
However, lactate must not be a burden to normal tissues if it's widely distributed and metabolized oxidatively, because it's the catabolism of glucose continued elsewhere (glucose →→ pyruvate → lactate → pyruvate →→ carbon dioxide + water).
"When control subjects were compared to the cancer patients, no significant difference was observed in the percentage of CO2 derived from lactate oxidation (21 ± 1.6 versus 25.3 ± 1.7%)."
"The percentage of the lactate production which was immediately oxidized was not related to the rate of lactate production, the mean values in the control subjects and cancer patients being 68.3 ± 2.7 and 62.1 ± 2.4%, respectively.
"Lactate disposal by mechanisms other than immediate oxidation, i.e., the difference between the lactate production rate and the oxidation rate, was significantly increased (p < 0.001) in the cancer patients (227 ± 24 versus 128 ± 8 μmol/sq m/min or 6.0 ± 0.7 versus 3.2 ± 0.3 μmol/kg/min)."
"The rate of nonoxidative lactate disposal was directly related to the lactate production rate (Chart 4). At least in part, conversion of lactate to glucose may account for the greater difference observed in the nonoxidative disposal in cancer patients in whom the percentage of glucose derived from lactate was significantly increased, (23.1 versus 15.8 ± 1.7%; p < 0.01). The percentage of glucose derived from lactate was also directly related to the lactate production rate (Chart 5)."
The burden comes when lactate reforms glucose, which occurs concentrated in specific organs. Not only the synthesis of glucose from lactate consumes more energy (–6ATP) than is produced (+2ATP) in the partial breakdown of glucose, but the energy produced may be left behind where breakdown occurred, making the site of clearance an exclusive energy consumer. Yet, the body has the option to oxidize it at any time in place of glucose to avoid ATP shortage.
But an additional concern is that glycogen is found in cancer cells as well, giving them metabolic independence to maintain activity when nutrients are scarce.
Cells go through cycles of depletion and repletion, and with excess lactate around, it's possible that part of it is channeled to glycogen synthesis. Therefore, we have to wonder where glucose resynthesis (through pyruvate carboxylase) is desirable.
An assumption is that tumor lactate stems only from cancer cells, but it can be formed in surrounding cells (fibroblasts or macrophages, for example) and cancer cells may exploit it to their advantage, whether in oxidizing it or as speculated above. It's also possible to have neighboring cancer cells fermenting and respiring in cooperation.
This adds a layer of complication in trying to explain the benefit of nutrient supplementation with a focus on local metabolism.
If online media outlets are much invested in optimizing the experience of readers while trying to stand out in a competitive market, why is it so difficult to find one using a similar default pattern (orange tone with blue titles)?
The current color gives it a drowsing appearance and adjusting this attribute to normal would already be a good tweak. The examples also include changes in font size, line length and space, italicized parts, and titles darkness. All are modifications that make a difference in repeated use and take minimal effort.
It's nice of Brad to offer personalized themes, but it's not practical to have hundreds of variations for each individual preference. The preferences can be subjective, yet we can't go wrong resembling Kvothe's state before the reversal of his vasectomy: sterile.
I never had issues uploading images. You can search for tools that convert Excel to Markdown tables, or go through a short tutorial to solve it in minutes.
@Mossy said in Your top daily supplement? If you had to pick just 1:
@LucH said in Your top daily supplement? If you had to pick just 1:
@Mossy said in Your top daily supplement? If you had to pick just 1:
There is no time frame recommended on that post for K2 to be taken before the D3. I was taking calcium acetate an hour before the D3. Do you have any thoughts on that before time frame?
well, I use logics:
1° you've understood why K2 has to be taken before A D3 K1 and K2 supplement, since K2 activates the dependent lipoproteins.
2. We need fats to assimilate lipoproteins. 35 g is required for vit K. Assimilation is proportional to the amount of fat.
So the time required is given by the digestive process. Roughly said 3 hours for fats but it could take more time if you get digestive problems, like a lack of enzymes or a lack of acidity to digest proteins.
3° Conclusion:Most of the time, I take K2 at breakfast.
When there is no cheese or ham (e.g.) I add 6-8 macadamia nuts. Not enough but it's OK.
At midday, I take Vit D3 5.000 UI.
Note: Once a week I begin with retinol 10 000 UI at breakfast, and K2 at midday, and D3 at supper. I should have begun with K2.
When I use tocopherols (2x/wk) I take a softgel (400 UI mixed toco) with a snack (low level of fat needed) if there is a problem.
Note: to be perfect: I should take K2 MK4 twice a day (half-life of type MK4 is shorter than MK7).
Mind with the type MK7: very fragile (oxidation). 3 months delay if not well encapsulated and protected with e.g. rosmarinusThank you LucH, for all the detail. I do only take K2 MK4, MK7 gives me heart issues. Wow, that is quite a bit of fat — 35 grams. I do remember Haidut recommending at least 14g of fat with fat soluble vitamins.
I see you don't mention taking calcium. Is that the case, that you don't supplement calcium along with A, D, and K2?
You can try to compensate for the lower absorption with a higher dose or through repetition. It's fine to waste some of it because it's what happens when vitamin K is obtained from plants. You'll be taking it in purified form, not having to deal with the food matrix. In this case, little fat is enough to make a difference.
Effect of dietary fat content on oral bioavailability of menatetrenone in humans
Note how the response to vitamin K with the lowest amount of fat in the meal was far from null and close to that with the average amount.
You may also stimulate bile discharge or supplement it:
To rely on topical supplementation is an option as well.
A while ago I suggested changes to the standard theme of the forum, for a plainer appearance. Since some members keep manifesting interest in modifying it and Brad proposed the creation of a poll, I'm sharing variations of what was in mind back then.
Current:
Alternatives:
It's difficult for admins to please everyone, but these modifications lean towards convention.
Massacration is an adored band where I live. People embrace their humor and worship them as heavy metal masters.
The context and lyrics are from Letras. It's a shame that you won't be able to catch some subtleties.
Massacration - Metal Is the Law
The Anthem of Metal: A Satirical Ode to Heavy Metal Culture
Massacration's song "Metal Is The Law" is a humorous and exaggerated tribute to the heavy metal subculture. The band, known for their satirical take on metal music, uses this song to both celebrate and poke fun at the rigid stereotypes and rules often associated with being a true metalhead. The lyrics are filled with hyperbolic commands and declarations, emphasizing the importance of adhering to the 'laws' of metal, such as wearing black and attending metal concerts.
The song opens with a repetitive chant, creating a ritualistic atmosphere that sets the tone for the rest of the track. The lyrics then dive into a series of exaggerated rules that one must follow to be considered truly metal. These rules include avoiding certain types of music and fashion choices, such as reggae, electronic music, and wearing shorts (bermuda). The use of terms like "boiolation" and "frescuration" adds a layer of absurdity, highlighting the band's comedic approach.
Massacration also takes a jab at other music genres and their fans, using derogatory language to emphasize the supposed superiority of metal. This is clearly a satirical exaggeration, meant to mock the elitist attitudes sometimes found within the metal community. The repeated phrase "Metal is the law" serves as both a rallying cry and a parody of the genre's often self-serious nature. By blending humor with a genuine love for metal, Massacration creates a song that both entertains and critiques the culture it celebrates.
Ai
Ai, ai, ai
Ai, ai, ai, ai, ai, ai, ai
Em cima, embaixo, puxa e vaiAi, ai, ai
Ai, ai, ai, ai, ai, ai, ai
Em cima, embaixo, puxa e vaiIf you want to be metal
The laws you got obey
The laws of Gods of metal
And that's what I'll say
Wow!If you want to be metal
No avacalhation
Use black forever
Go to the show of MassacrationNo! Boiolation!
Frescuration!
Viadation!Die! Reggae idiota!
Mambo escroto!
Forró babaca!Metal is the law
The law is the metal
Metal the law is
Metal
Wow!Now that you are metal
Metal you are
Never, never, never, never, never
Use bermudaNo! Boiolation!
Frescuration!
Viadation!Die! Música eletrônica de bicha!
Pop de viados!
Dance, no!Metal is the law
The law is the metal
Metal the law is
Metal
Wow!
Massacration - Metal Is My Life
The Anthem of Metal Devotion
Massacration's song "Metal Is My Life" is a humorous and exaggerated ode to the genre of heavy metal. The lyrics are filled with hyperbolic comparisons, placing metal above various beloved and essential aspects of life, such as food, technology, and even sex. The song's playful tone and over-the-top declarations reflect the band's satirical approach to music, often poking fun at the stereotypes and clichés associated with heavy metal culture.
The repeated assertion that "metal is my life" serves as a mantra for the die-hard metal fan, emphasizing the genre's importance and centrality in their existence. By comparing metal to lasagna, sushi, and even Google, the song humorously elevates the genre to a status of utmost importance, suggesting that nothing else can compare to the power and satisfaction that metal provides. This exaggeration is a common trope in Massacration's music, which often blends comedy with a genuine love for metal.
The lyrics also touch on the communal and energetic aspects of metal culture. Phrases like "bang the head, abre a rodinha, put pro alto a mãozinha" highlight the physical and social activities associated with metal concerts, such as headbanging and moshing. The call to "no vacilation, vem com o Massacration" invites listeners to join in the fun and embrace the metal lifestyle without hesitation. This sense of community and shared passion is a key element of the metal scene, and the song captures this spirit with its lively and inclusive message.
Overall, "Metal Is My Life" is a celebration of heavy metal's unique culture and the unwavering dedication of its fans. Through its humorous and exaggerated lyrics, the song pays tribute to the genre's power, energy, and sense of community, making it an anthem for metal enthusiasts everywhere.
Metal is my life
Metal is my lifeMetal is better than lasanha
And look, I'm família italiana
Metal is important to me
'Cause metal is better than sushiMetal is my life
Metal is my lifeMetal is better than Xvideos
And look, I'm very punhetation
Metal is better than Google
Metal é melhor que essas coisa tudoMetal is my life
Metal is my lifeNo Guaraná, no chocolate
Eu quero é se divertir
Guitar no retorno, bota mais alto pra mim
Bang the head, abre a rodinha, put pro alto a mãozinha
No vacilation, vem com o MassacrationMetal is my life
'Cause metal is my life
Metal is my life
Metal is my lifeMetal is power and success
Metal is better than sex
The Mischievous Power of the 'Evil Papagali'
Massacration's song 'Evil Papagali' is a humorous and exaggerated tale of a demonic parrot that embodies the spirit of heavy metal. The lyrics introduce us to a small bird that has come from hell, bringing with it a rebellious and violent nature. This parrot, being unable to fly, is described as enjoying fighting and killing, which adds a layer of dark comedy to the song. The bird's demand for 'biscoito' (Portuguese for 'cracker') further emphasizes its quirky and absurd character.
The song's narrative is filled with playful contradictions and over-the-top imagery. The parrot, referred to as 'Evil Papagali,' is portrayed as a powerful and malevolent creature, yet it also has mundane desires like wanting a cookie. This juxtaposition creates a satirical tone, poking fun at the often serious and intense themes found in heavy metal music. The repeated chant of 'Loro quer biscoito' (Polly wants a cracker) serves as a catchy and humorous refrain that contrasts with the otherwise dark and aggressive imagery.
'Evil Papagali' also reflects Massacration's signature style, which blends heavy metal with comedic elements. The band is known for its parody of metal culture, and this song is a perfect example of their approach. By creating a character like the 'Evil Papagali,' Massacration not only entertains but also critiques the genre's sometimes self-serious nature. The song's energetic and chaotic structure, with its thrash and mosh elements, mirrors the wild and unpredictable behavior of the titular parrot, making it a memorable and engaging piece.
Thrash
MoshI met a bird that
Came from hell
He is little green
He is very wellHe likes to play
He likes the milk
He likes to fight
He likes to killI met a bird that
Came from hell
He is little green
He is very wellHe cannot fly
And he is revolt
He don't like me
And then he told
What?Loro, loro quer biscoito
Quer biscoitoEvil papagali
He wants to kill
He ordered me to
Puta que pariuEvil papagali
He is animal
He got the power
Of heavy metalHe's got the power
Of the furation
You feel the pain
It's the bicationHe's master of hell
We are Massacration
He wants to speak
To all the nation
ListenLoro, loro quer biscoito
Quer biscoitoCurupaco, feel the fire
Curupaco, feel
Curupaco, kill with power
Curupaco, kill theLoro (loro), loro quer biscoito
Come on
Loro (loro), loro quer biscoitoLoro, loro quer biscoito
Loro (loro), loro quer biscoito
Quer biscoitoThrash
Mosh
Thrash, mosh
We know from Ray and other authors that thiamin, niacin, and aspirin have therapeutic potential in cancer. It seems that biotin was included in the combination without much consideration, and Jorge had access to more promising options already in his store.
I know that the priority is to nourish the person, but it's most effective when we limit nourishment to cancer cells. Biotin is a vitamin whose anabolic functions prevail, making supplementation a questionable intervention.
The assumption might have been that if pyruvate dehydrogenase (PDH) is inhibited, the alternative means to metabolize pyruvate away from lactate would be with the biotin-dependent pyruvate carboxylase (PC) to oxaloacetate.
Mitochondria are not just energy-producing organelles, they're also biosynthetic sites, with pyruvate carboxylase having an important role in this anabolic picture.
Oxaloacetate can help to export excess mitochondrial acetyl-CoA (that reinforces PDH inhibition and stimulates PC). This acetyl-CoA can then be used to synthesize fats in the cytosol, a process that's started by acetyl-CoA carboxylase (ACC)--another biotin-dependent enzyme.
Roles of pyruvate carboxylase in human diseases: from diabetes to cancers and infection
Yes, PC-derived oxaloacetate can refill the TCA cycle, but so does ketoglutarate from glutamate or glutamine, and they can cooperate.
Two other biotin-dependent enzymes (MCC and PCC) are involved in amino acid metabolism and can also channel the products to refill the cycle. These products would enter the TCA cycle right where ATP is synthesized through substrate-level phosphorylation (Tommy), with higher chances of bypassing inhibitions.
Therefore, all 4 biotin enzymes can converge in anabolic processes that may be problematic in the context of cancer.
To compound the concerns, simple conversion of pyruvate to oxaloacetate is one step away from aspartate synthesis, needed for the upregulated nucleotide synthesis.
This aspartate can also participate in the malate-aspartate shuttle, that serves to import cytosolic NADH. Normally, oxalate is formed from malate, but if this is reversed with the help of pyruvate carboxylase, the shuttle could perhaps work in reverse, and it would contribute to the export of NADH, with higher cytosolic NADH/NAD⁺ promoting lactate synthesis. In addition, it can be an alternative way to regenerate NAD⁺ when respiratory complexes are compromised, to allow the TCA cycle to keep functioning.
In fairness, some of these processes concentrate in liver and kidneys, and biotin may also relieve the burden in supporting clearance of excess lactate from cancerous tissues (lactate → pyruvate –B7→ oxaloacetate → pyruvate enolphosphate →→ glucose), possibly more so than thiamin, as local pyruvate oxidation without redistribution as glucose could perhaps overwhelm such organs. However, thiamin could be of better service for other tissues, that clear lactate through complete oxidation.
Even in cases where biotin supplementation normalizes glucose metabolism, the anabolic component can't be discarded.
Some Aspects of Carbohydrates Metabolism in Biotin-Deficient Rats
"It is possible, therefore, that these changes in the fatty acid composition of the lipid might alter the structural integrity of mitochondria with the consequent effect on oxidative phosphorylation. This defect, as reflected by amino acid incorporation studies, was compensated during early stages of the deficiency when the animals received an oxidizable substrate such as succinate (see reference 1) or fructose or sorbitol in the basal diet. It is, therefore, possible that a moderate decrease in oxidative phosphorylation does not limit the efficiency of the biotin-deficient animal as long as adequate levels of oxidizable substrates are maintained. However, in advanced deficiency as observed after 8 weeks on the deficient diet, succinate, sorbitol, or fructose feeding did not help the animal. Only administration of biotin restwed fatty acid synthesis and the integrity of mitochondria for normal oxidative phosphorylation."
It's no wonder that symptoms of biotin deficiency point to anabolic defects, such as disturbed skin lipids.
I would be careful with its supplementation in advanced cancer and observe reactions. It's preferable to avoid B-vitamins formulas and have the vitamins separately for better control.
This is not to suggest that thiamin, niacin, and aspirin are entirely beneficial in cancer because they're not, but their positive outweigh negative effects. Biotin isn't invariably problematic, but seems riskier.
