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Research highlights disrupted NAD(H) homeostasis as a potential therapeutic target to combat tuberculosis (Nicotinamide reduces TB by 90%)
Medical Xpress / University of Alabama at Birmingham / Nature Communications ^ | Nov. 20, 2023 | Jeff Hansen / Hayden T. Pacl et al

Posted on 11/23/2023 10:39:44 AM PST by ConservativeMind

It has been uncertain how Mycobacterium tuberculosis deflects the immune response in humans, though evidence has pointed to host immunometabolism—the intrinsic link between metabolism in immune cells and their immune function.

Now a study shows how M. tuberculosis perturbs homeostasis of the high-energy molecule NADH and reprograms glycolysis in myeloid cells. This highlights glycolysis as a potential therapeutic target to combat the world's leading infectious disease killer.

Glycolysis is the pathway that converts glucose into pyruvate while forming the high-energy molecules ATP and NADH.

The reversible process of lactate fermentation is catalyzed by the enzyme lactate dehydrogenase, or LDH. LDH has four subunits, a mix of LDHA and LDHB subunits.

The LDHA-deficient mice, when infected with a low dose of M. tuberculosis, were more susceptible to infection and had a significantly reduced survival time.

"This suggests that LDHA is necessary for protection against tuberculosis and that glycolytic flux in myeloid cells is essential for the control of M. tuberculosis infection and disease," Steyn said.

Bioenergetics experiments showed mouse macrophages require LDHA and its LDH-mediated NAD+ regeneration for their metabolic response to interferon-gamma.

Since NAD+ depletion appeared to be central to the glycolytic inhibition caused by M. tuberculosis, the researchers asked whether the addition of an NAD+ precursor, nicotinamide, would alter the ability of macrophages to mount an immune response.

In a mouse model, feeding the mice nicotinamide for four weeks, beginning either three days or 28 days post-infection, showed a tenfold reduction of the M. tuberculosis burden in the lungs, and it also reduced inflammation in the lungs.

"We have provided further evidence of a host-dependent effect of nicotinamide, the metabolic requirements for its activity and a modern-day demonstration of its efficacy as a treatment for tuberculosis, using two treatment regimens in vivo," Steyn said.

(Excerpt) Read more at medicalxpress.com ...


TOPICS: Health/Medicine
KEYWORDS: nicotinamide; tb
Nicotinamide helped natural body processes clear 90% of TB in mice.

The amount was far greater than would ever be used with people, but this process was a proof of concept.

It’s possible it could have been just as successful with a smaller amount.

1 posted on 11/23/2023 10:39:44 AM PST by ConservativeMind
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To: ConservativeMind
From Health.com:

Unless prescribed by a medical provider, you should generally avoid taking high-dose nicotinamide supplements, such as those that provide more than 500 mg per day.

Is Nicotinamide Safe?

Nicotinamide is generally well-tolerated. It's known to be safe in doses of 35 mg or less, and possibly safe in doses of 900-1500 mg daily.

When taken in high doses over three grams (3,000 mg) per day, nicotinamide can cause serious side effects such as nausea, vomiting, and liver issues.

https://www.health.com/nicotinamide-benefits-7561633

2 posted on 11/23/2023 10:42:26 AM PST by ConservativeMind (Trump: Befuddling Democrats, Republicans, and the Media for the benefit of the US and all mankind.)
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To: Mazey; ckilmer; goodnesswins; Jane Long; BusterDog; jy8z; ProtectOurFreedom; matthew fuller; ...

The “Take Charge Of Your Health” Ping List

This high volume ping list is for health articles and studies which describe something you or your doctor, when informed, may be able to immediately implement for your benefit.

Email me to get on either the “Common/Top Issues” (20 - 25% fewer pings) or “Everything” list.

3 posted on 11/23/2023 10:50:01 AM PST by ConservativeMind (Trump: Befuddling Democrats, Republicans, and the Media for the benefit of the US and all mankind.)
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To: ConservativeMind

Wish I knew this when my TB erupted 5 years ago. TB itself is pretty rare in this country. I presumedly was exposed back in my 20’s when I worked construction in Miami and many of the other workers were Haitian or other illegals. It basically sat dormant until I turned 62 and then went fulminant. Just one more reason to keep illegals out of this country.


4 posted on 11/23/2023 11:08:12 AM PST by jimwatx
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To: ConservativeMind

I take about 2-3 grams each of niacinamide and extended release niacin daily plus roughly equal amounts of TMG. Half in the morning half in the evening.

I started doing that 4-5 months ago. I really like the way I feel when I do that.


5 posted on 11/24/2023 9:03:51 AM PST by ckilmer (ui)
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To: ckilmer; ConservativeMind; Tilted Irish Kilt; metmom; Qiviut; goodnesswins; SeekAndFind

Does anyone have information on the relative effectiveness and dosage of niacin, niacinamide, and nicotinamide when used for health improvement? Are amides of niacin and nicotine even in the same supplement family? Regarding feeling good using high niacin type supplements, decades ago I remember reading about using such high doses for mental health purposes and perhaps even schizophrenia (sp?).


6 posted on 11/24/2023 10:40:41 AM PST by gleeaikin ( Question authority)
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To: ckilmer

What is TMG?


7 posted on 11/24/2023 11:54:26 AM PST by goodnesswins ( We pretend to vote and they pretend to count the votes.)
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To: goodnesswins

TMG=trimethylglycine
google
why do you need to take TMG supplement with niacin supplement?

Answer

Trimethylglycine (TMG), also known as betaine, is sometimes taken in conjunction with niacin (vitamin B3) supplements for several reasons:

Methylation support: TMG is involved in the methylation process in the body, which is crucial for various biochemical reactions, including the conversion of homocysteine to methionine. Niacin also plays a role in these methylation pathways. By taking TMG and niacin together, some individuals believe they can support these processes more effectively.

Homocysteine management: Elevated levels of homocysteine in the blood are associated with an increased risk of cardiovascular disease. Both TMG and niacin can help lower homocysteine levels through different mechanisms. TMG donates methyl groups, while niacin is involved in the formation of compounds that can convert homocysteine to less harmful substances.

Synergistic effects: Some people believe that taking TMG and niacin together may have synergistic effects in promoting heart health and reducing the risk of certain health issues. However, scientific evidence supporting this specific combination is limited and inconclusive.

It’s important to note that the use of supplements should be discussed with a healthcare provider, as individual needs and responses to supplements can vary. Additionally, high doses of niacin can cause side effects, such as flushing and liver issues, so it’s essential to follow recommended dosages and consult a healthcare professional for guidance on supplementation. They can assess your specific health needs and help you determine whether TMG and niacin supplementation is appropriate for you.


8 posted on 11/24/2023 12:00:49 PM PST by ckilmer (ui)
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To: ckilmer

Thanks...we take Betaine with HCL


9 posted on 11/24/2023 5:59:24 PM PST by goodnesswins ( We pretend to vote and they pretend to count the votes.)
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