haidut

Member
Joined
Mar 18, 2013
Messages
17,943
Location
USA / Europe
The study used both rodent model but the scientists are confident the results fully apply to humans. The rodent model was used to test niacinaide as an actual treatment for pre-eclampsia, not as prevention. The next step is to conduct a human-only trial with niacinamide as a treatment of the entire pre-eclampsia cascade, covering both mother and baby.
The human equivalent doses of niacinamide, as the study itself says, was 2.5g daily. As the study also says, this is below the 3g daily limit beyond which liver side effects could occur with niacinamide intake. So, if the human trial also confirms this, niacinamide could join progesterone as the only other known chemical capable of treating this deadly condition (for both mother and baby).
Another interesting finding is that niacinamide reduced entothelial dysfunction and as such lowered the blood pressure of the ill mice. Since the mechanism in most cases of elevated blood pressure is very similar (if not the same) niacinamide could be a safe OTC treatment for blood pressure in general.
While the proposed mechanism of action for niacinamide again involves raising NAD (and opposing ADPR, sFLT1), I think niacinamide's other effects in opposing estrogen and cortisol (just like progesterone does) should not be ignored as possible reasons as estrogen and cortisol are quite detrimental for pregnancy.
Niacinamide Is Anti-estrogenic
Niacinamide Lowers Cortisol

Hopefully, next steps would be a clinical trial with a few active groups using niacinamide, progesterone, vitamin E, and a combination of these. Measuring estrogen and cortisol would help determine additional mechanisms of action for niacinamide as I don't think NAD is the whole story.

http://medicalxpress.com/news/2016-12-potential-treatment-pregnant-women-preeclampsia.html
"...Scientists in Japan and the US have found that vitamin B3 nicotinamide may help treat pregnant women who suffer from preeclampsia by preventing strokes and in some cases, even stimulating the growth of their fetus. Up to 8% of pregnant women suffer from preeclampsia, a deadly disease characterized by high blood pressure, blood vessel damage, high levels of protein in the urine and fluid retention that causes swelling in the legs and feet. In some cases, preeclampsia is also believed to restrict a fetus' growth. Blood pressure-lowering drugs do not improve blood vessel damage. In fact, they reduce blood supply to the babies, which could lead to fetal death. Until now, the only treatment for preeclampsia-affected pregnant women has been delivery of the baby. Now, researchers at Tohoku University, in collaboration with US scientists, have found that nicotinamide - also referred to as Vitamin B3 - relieves preeclampsia in mouse models. Moreover, they have also discovered that nicotinamide can even improve fetal growth in mothers with preeclampsia. "We had previously shown that endothelin, a strong vessel narrowing hormone, worsens preeclampsia. But inhibiting the hormone is harmful to the babies," says Associate Professor Nobuyuki Takahashi of Tohoku University's Graduate School of Pharmaceutical Sciences, who co-led the study. "In contrast, nicotinamide is generally safe to mothers and babies, corrects the blood vessel narrowing effect of endothelin, and reduces stress to the babies. Accordingly, we evaluated the effects of nicotinamide using two mouse models of preeclampsia caused by different mechanisms." The researchers concluded that nicotinamide is the first safe drug that lowers blood pressure, reduces urine protein and alleviates blood vessel damage in preeclampsia-affected mice. The researchers went on to show that in many cases, nicotinamide also prevents miscarriage, prolongs pregnancy period and improves the growth of the babies in mice with preeclampsia. "Nicotinamide merits evaluation for preventing and treating preeclampsia in humans," says Oliver Smithies, a Weatherspoon Eminent Distinguished Professor at the University of North Carolina at Chapel Hill. Smithies is a Nobel Laureate in Physiology or Medicine, and co-leader of this study. The research team hopes that if the treatment works in humans, nicotinamide could help treat preeclampsia and prevent fetal growth restriction associated with the disease in pregnant women."

Nicotinamide benefits both mothers and pups in two contrasting mouse models of preeclampsia. - PubMed - NCBI
"...To explore the potential of nicotinamide for treating PE, we first evaluated its effects on the PE-like condition induced in nonpregnant female inbred strain C57BL/6J mice by administrating 109 plaque forming units (pfu) of a recombinant adenovirus, rAdV Flt1(1-3), that infects the liver and causes production of Flt1(1-3) and increases its concentration in the plasma (7). [Flt(1-3) is a synthetic protein that includes a signal sequence, the first 328 amino acids of FLT1, and six copies of a His tag.] These experiments showed that 500 mg/kg per day of oral nicotinamide has significant beneficial effects on the hypertension, albuminuria, damage to the endothelium of the renal glomerular capillaries, and glomerular mesangial expansion caused by the Flt1(1-3) (Fig. S1). [The amount of nicotinamide used in these and all of our other experiments (500 mg/kg per day) is equivalent to 2.5 g/d in a 60-kg human, when corrected for body surface area (8), and consequently does not exceed doses (3–9 g daily) that are commonly used (9, 10).]

"...Fig. S6 presents diagrammatically an overview of the pathways via which nicotinamide may benefit both mothers and pups in our two contrasting mouse models of PE. Nicotinamide inhibits ADPR cyclase, relaxes blood vessels constricted by sFLT1 (2, 3), and improves the condition of the endothelium, thereby correcting the hypertension and the albuminuria caused in the mothers by PE. At the same time, acting through the NAD+ salvage pathway, it improves the metabolic state of hypoxic embryos, normalizes their production of ATP, and prevents FGR. Nicotinamide probably ameliorates the consequences of PE-associated ischemia in the same way that it protects the heart from ischemic reperfusion injury (25)."
 
Last edited:

haidut

Member
Thread starter
Joined
Mar 18, 2013
Messages
17,943
Location
USA / Europe

Wow, so endotoxin striked once again huh!? From the study you sent:
"...PE was classically referred to as endotoxemia or toxemia of pregnancy, and it is ironic that it seems that LPS and other microbial endotoxins really are involved. Overall, the recognition of an infectious component in the etiology of PE mirrors that for ulcers and other diseases that were previously considered to lack one."

No wonder niacinamide helps, it acts acts as a functional endotoxin antagonist. I guess this means more direct TLR4 antagonists like ketotifen, cyproheptadine, naltrezone, etc can probably treat it as well.
 

Koveras

Member
Joined
Dec 17, 2015
Messages
719
The study used both rodent model but the scientists are confident the results fully apply to humans. The rodent model was used to test niacinaide as an actual treatment for pre-eclampsia, not as prevention. The next step is to conduct a human-only trial with niacinamide as a treatment of the entire pre-eclampsia cascade, covering both mother and baby.
The human equivalent doses of niacinamide, as the study itself says, was 2.5g daily. As the study also says, this is below the 3g daily limit beyond which liver side effects could occur with niacinamide intake. So, if the human trial also confirms this, niacinamide could join progesterone as the only other known chemical capable of treating this deadly condition (for both mother and baby).
Another interesting finding is that niacinamide reduced entothelial dysfunction and as such lowered the blood pressure of the ill mice. Since the mechanism in most cases of elevated blood pressure is very similar (if not the same) niacinamide could be a safe OTC treatment for blood pressure in general.
While the proposed mechanism of action for niacinamide again involves raising NAD (and opposing ADPR, sFLT1), I think niacinamide's other effects in opposing estrogen and cortisol (just like progesterone does) should not be ignored as possible reasons as estrogen and cortisol are quite detrimental for pregnancy.
Niacinamide Is Anti-estrogenic
Niacinamide Lowers Cortisol

Hopefully, next steps would be a clinical trial with a few active groups using niacinamide, progesterone, vitamin E, and a combination of these. Measuring estrogen and cortisol would help determine additional mechanisms of action for niacinamide as I don't think NAD is the whole story.

http://medicalxpress.com/news/2016-12-potential-treatment-pregnant-women-preeclampsia.html
"...Scientists in Japan and the US have found that vitamin B3 nicotinamide may help treat pregnant women who suffer from preeclampsia by preventing strokes and in some cases, even stimulating the growth of their fetus. Up to 8% of pregnant women suffer from preeclampsia, a deadly disease characterized by high blood pressure, blood vessel damage, high levels of protein in the urine and fluid retention that causes swelling in the legs and feet. In some cases, preeclampsia is also believed to restrict a fetus' growth. Blood pressure-lowering drugs do not improve blood vessel damage. In fact, they reduce blood supply to the babies, which could lead to fetal death. Until now, the only treatment for preeclampsia-affected pregnant women has been delivery of the baby. Now, researchers at Tohoku University, in collaboration with US scientists, have found that nicotinamide - also referred to as Vitamin B3 - relieves preeclampsia in mouse models. Moreover, they have also discovered that nicotinamide can even improve fetal growth in mothers with preeclampsia. "We had previously shown that endothelin, a strong vessel narrowing hormone, worsens preeclampsia. But inhibiting the hormone is harmful to the babies," says Associate Professor Nobuyuki Takahashi of Tohoku University's Graduate School of Pharmaceutical Sciences, who co-led the study. "In contrast, nicotinamide is generally safe to mothers and babies, corrects the blood vessel narrowing effect of endothelin, and reduces stress to the babies. Accordingly, we evaluated the effects of nicotinamide using two mouse models of preeclampsia caused by different mechanisms." The researchers concluded that nicotinamide is the first safe drug that lowers blood pressure, reduces urine protein and alleviates blood vessel damage in preeclampsia-affected mice. The researchers went on to show that in many cases, nicotinamide also prevents miscarriage, prolongs pregnancy period and improves the growth of the babies in mice with preeclampsia. "Nicotinamide merits evaluation for preventing and treating preeclampsia in humans," says Oliver Smithies, a Weatherspoon Eminent Distinguished Professor at the University of North Carolina at Chapel Hill. Smithies is a Nobel Laureate in Physiology or Medicine, and co-leader of this study. The research team hopes that if the treatment works in humans, nicotinamide could help treat preeclampsia and prevent fetal growth restriction associated with the disease in pregnant women."

Nicotinamide benefits both mothers and pups in two contrasting mouse models of preeclampsia. - PubMed - NCBI
"...To explore the potential of nicotinamide for treating PE, we first evaluated its effects on the PE-like condition induced in nonpregnant female inbred strain C57BL/6J mice by administrating 109 plaque forming units (pfu) of a recombinant adenovirus, rAdV Flt1(1-3), that infects the liver and causes production of Flt1(1-3) and increases its concentration in the plasma (7). [Flt(1-3) is a synthetic protein that includes a signal sequence, the first 328 amino acids of FLT1, and six copies of a His tag.] These experiments showed that 500 mg/kg per day of oral nicotinamide has significant beneficial effects on the hypertension, albuminuria, damage to the endothelium of the renal glomerular capillaries, and glomerular mesangial expansion caused by the Flt1(1-3) (Fig. S1). [The amount of nicotinamide used in these and all of our other experiments (500 mg/kg per day) is equivalent to 2.5 g/d in a 60-kg human, when corrected for body surface area (8), and consequently does not exceed doses (3–9 g daily) that are commonly used (9, 10).]

"...Fig. S6 presents diagrammatically an overview of the pathways via which nicotinamide may benefit both mothers and pups in our two contrasting mouse models of PE. Nicotinamide inhibits ADPR cyclase, relaxes blood vessels constricted by sFLT1 (2, 3), and improves the condition of the endothelium, thereby correcting the hypertension and the albuminuria caused in the mothers by PE. At the same time, acting through the NAD+ salvage pathway, it improves the metabolic state of hypoxic embryos, normalizes their production of ATP, and prevents FGR. Nicotinamide probably ameliorates the consequences of PE-associated ischemia in the same way that it protects the heart from ischemic reperfusion injury (25)."

Following up on this and this

With these on the role of serotonin, other tryptophan metabolites, and free fatty acids in pre-eclampsia and preterm birth. Speaks further to the benefits of niacinamide and aspirin in attenuating the FFA/NEFA and stress responses here.

Can serum free fatty acids assessment predict severe preeclampsia?


Fasting serum triglycerides, free fatty acids, and malondialdehyde are increased in preeclampsia, are positively correlated, and decrease within 48 hours post partum.

Nonesterified fatty acids and spontaneous preterm birth: a factor analysis for identification of risk patterns.

[Study on serotonin metabolism in toxemia of pregnancy].

Maternal tryptophan and kynurenine pathway metabolites and risk of preeclampsia.

Nonesterified fatty acids and spontaneous preterm birth: a factor analysis for identification of risk patterns.
 

haidut

Member
Thread starter
Joined
Mar 18, 2013
Messages
17,943
Location
USA / Europe

Thanks.
Do you have anything on adequate protein or salt for eclampsia? Peat quotes this a few times as a well-known old medical remedy used in hospitals in the early 20th century but I have not been able to find much.
 

sugarbabe

Member
Joined
Sep 13, 2012
Messages
3,565
Location
USA
Dr. Tom Brewer treated this with adequate nutrition. He calls it a condition of malnutrition. Not meeting the demands for the added blood volume and stressing the kidneys to supply that volume.
 

Koveras

Member
Joined
Dec 17, 2015
Messages
719
Thanks.
Do you have anything on adequate protein or salt for eclampsia? Peat quotes this a few times as a well-known old medical remedy used in hospitals in the early 20th century but I have not been able to find much.

"Even a slight increase in protein intake can markedly increase calcium retention." -Adelle Davis

The effect of protein on calcium balance seems controversial, with some earlier studies showing increased calcium excretion in the urine with higher protein intakes. This increased urinary excretion seems to be counterbalanced by reduced fecal excretion and increased intestinal absorption.

There are some confounders but I think increased calcium retention with higher protein intake might have the effect of reducing serotonin, prolactin, PTHrP, and PTH. These are all part of the counter-regulatory response to stress/hypoglycaemia (along with the usual suspects adrenaline, noradrenaline, glucagon, cortisol, growth hormone, etc) and all have the effect of increasing lipolysis - which fits along with with the studies I posted above relating to FFAs. Closest to calcium balance, serotonin and prolactin especially have an effect on blood pressure probably relevant to preeclampsia.

Is there an effect of sodium in keeping calcium extracellular?

Endocrinology. 2010 Mar;151(3):1071-8. doi: 10.1210/en.2009-0744. Epub 2010 Feb 10.
The effect of dietary protein on intestinal calcium absorption in rats.
Gaffney-Stomberg E1, Sun BH, Cucchi CE, Simpson CA, Gundberg C, Kerstetter JE, Insogna KL.

Increasing dietary protein intake in humans acutely increases urinary calcium. Isotopic absorption studies have indicated that, at least in the short term, this is primarily due to increased intestinal Ca absorption. To explore the mechanisms underlying dietary protein's effect on intestinal Ca absorption, female Sprague Dawley rats were fed a control (20%), low (5%), or high (40%) protein diet for 7 d, and Ca balance was measured during d 4-7. On d 7, duodenal mucosa was harvested and brush border membrane vesicles (BBMVs) were prepared to evaluate Ca uptake. By d 7, urinary calcium was more than 2-fold higher in the 40% protein group compared with control (4.2 mg/d vs. 1.7 mg/d; P < 0.05). Rats consuming the 40% protein diet both absorbed and retained more Ca compared with the 5% protein group (absorption: 48.5% vs. 34.1% and retention: 45.8% vs. 33.7%, respectively; P < 0.01). Ca uptake was increased in BBMVs prepared from rats consuming the high-protein diet. Maximum velocity (V(max)) was higher in the BBMVs prepared from the high-protein group compared with those from the low-protein group (90 vs. 36 nmol Ca/mg protein x min, P < 0.001; 95% CI: 46-2486 and 14-55, respectively). The Michaelis Menten constant (K(m)) was unchanged (2.2 mm vs. 1.8 mm, respectively; P = 0.19). We conclude that in rats, as in humans, acute increases in protein intake result in hypercalciuria due to augmented intestinal Ca absorption. BBMV Ca uptake studies suggest that higher protein intake improves Ca absorption, at least in part, by increasing transcellular Ca uptake.​
 
Similar threads
Thread starter Title Forum Replies Date
haidut High-dose Vitamin C Or Niacinamide May Treat Advanced Colon Cancer Scientific Studies 12
haidut Rheumatoid Arthritis Is A Metabolic Disease; Vitamin K And Niacinamide May Treat It Scientific Studies 57
charlie Vitamin B3 (Niacinamide) Shows Promise For Glaucoma Patients In Clinical Trial Scientific Studies 2
haidut Niacinamide (vitamin B3) May Cure HIV (human Study) Scientific Studies 10
charlie Caffeine, vitamin E, and niacinamide are known to reduce.... Ray Peat Quotes 6
Hans Vitamin D3 and vit C resolved COVID-19 pneumonia in 3 days Scientific Studies 13
A COVID-19 and Vitamin A Ask For Help or Advice 1
Peatogenic Magnesium activates Vitamin D Testimonials 5
jpgio Vitamin E makes me feel alive Supplements, Pharmaceutical Drugs 10
E Vitamin D hypersensitivity Ask For Help or Advice 28
limitless77 Vitamin k2 mk4 vs mk7 and dosage? Supplements, Pharmaceutical Drugs 0
bzmazu The neuroprotective effect of vitamin E on chronic sleep deprivation-induced memory impairment E 0
bzmazu Excess vitamin intake: An unrecognized risk factor for obesity Vitamins 4
Mito Vitamin D and COVID-19 - Chris Masterjohn AHS 2021 D 8
miquelangeles Vitamin K and brain function K 3
haidut Vitamin D, reducing fat oxidation may treat lung fibrosis, COVID-19 Scientific Studies 5
haidut Human study - vitamin B1 safe & effective for preventing & treating Alzheimer Disease (AD) Scientific Studies 18
J Vitamin C I.V Intravenous Protocol Cancer 1
yerrag Good Vitamin E Resources From The Past Being Cancelled: Can We Have a Repository Here? E 86
Hans Should you quit coffee to fix a vitamin B1 deficiency? Articles & Scientific Studies 26
J Think I may have vitamin D toxicity Skin 15
K Quit Vitamin E Cold Turkey? Vitamins 6
Mito Vitamin K Intake and Atherosclerotic Cardiovascular Disease in the Danish Diet Cancer and Health Study K 4
ecstatichamster Report any side effects from vitamin K2 here Supplements, Pharmaceutical Drugs 27
GorillaHead Vitamin A! How does one mitigate the damage of too much ? Ask For Help or Advice 19
RenaissanceMan Vitamin K alleviates the reduction in testosterone production induced by Endotoxin (lipopolysaccharide) administration in rat testis K 0
L Vitamin D makes nipples hurt Vitamins 13
ecstatichamster Lost Story of Vitamin E: Shute family that Dr. Peat referred to and estrogen research Ray Peat Topics 1
jpgio Consistent Negative reaction to foods high in vitamin A or beta carotene Fat-Soluble Vitamins 5
RenaissanceMan Thorne's Vitamin E really upsets my stomach E 3
hazel Vitamin e for perimenopausal woman Vitamins 5
haidut Vitamin B1 can reverse heart damage/failure caused by alcoholism Scientific Studies 6
GorillaHead Is this study about vitamin A most likely a lie to protect the use of isotretinoin? Skin 1
G What vitamin deficiencies lead to acne? Ask For Help or Advice 4
haidut Vitamin D improves ovarian reserves in women with infertility Scientific Studies 1
haidut Vitamin E 100-fold more potent than remdesivir for SARS-CoV-2 / coronaviruses Scientific Studies 102
F Pasteurized squeezed orange juice mineral/vitamin content? Ask For Help or Advice 1
G How do animals make vitamin B12 Vitamins 1
Lenny Vitamin K and aspirin, how to proceed? Ask For Help or Advice 8
C Do you still get vitamin D on a fully cloudy sky? D 17
M Help me reduce my vitamin D levels Ask For Help or Advice 28
S Vitamin E dose for lowering estrogen and prolactin? Supplements 14
youngsinatra Vitamin A + Iron Supplementation As Effective As TRT In Puberty-Delayed Individuals Male Issues 1
md_a Vitamin D, Calcium and mineral metabolism with Dr Ray Peat and Kate Deering Interviews 6
haidut High PTH, low vitamin D implicated in bipolar disorder (BD) Scientific Studies 2
haidut Vitamin B6, lowering stress, may treat schizophrenia Scientific Studies 3
haidut Vitamin D (topical) safe and effective for removing scars Scientific Studies 2
haidut Vitamin D deficiency impairs muscles by lowering energy production Scientific Studies 2
Pistachio Vitamin D3 perpetual thread (for-and-against testmonials) Supplements 41
S Feeling worse with sun instead of vitamin D supp? Ask For Help or Advice 42

Similar threads

Top