#72

If I remember properly, niacin was the go-to standard of care for treating arteriosclerosis before statins. However, they found that even though cholesterol levels were reduced with niacin, deaths due to heart disease did not go down.

Then statins were invented and everything changed.

It seems a bit backward going back to Niacin which looks great at first, but in the end doesn’t work to reduce mortality.

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#73

As I understand it, the consensus of experts no longer recommends niacin. Even if something lowers Lp(a), the side effects can still be greater —> does not reduce mortality. I have high Lp(a).

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#74

From the Atherosclerosis Journal. Published:January 31, 2024

https://www.atherosclerosis-journal.com/article/S0021-9150(24)00029-7/abstract?uuid=uuid%3A30707e9d-e11d-472e-9071-53625fb208e1

Methods

Participants of the Dallas Heart Study (DHS), a multi-ethnic cohort of ambulatory individuals at low-intermediate risk for future atherosclerotic cardiovascular disease (ASCVD), who had their blood tested for 31 biomarkers reflecting multiple pathophysiological pathways, underwent 2 serial non-contrast computed tomography assessments for CAC a median ∼7 years apart. The collected biomarkers were explored for association with CAC incidence or progression using univariate and multivariate analysis.

Results

A total of 1424 participants were included; mean age 43 years, 39 % male, and nearly half African-American. Over a 7-year interval between the two CAC measurements, 340 participants (23.9 %) had CAC incidence or progression, 105 (7.4 %) with incident CAC, and 309 (21.7 %) with CAC progression. Although several plasma biomarkers were associated with CAC incidence or progression in a univariate model, only soluble intercellular adhesion molecule-1 (sICAM-1), related to atherosclerosis by the inflammatory pathway, remained independently associated in a multivariate model adjusted for traditional risk factors.

Conclusions

Further studies are needed to characterize the role of sICAM-1 in CAC evolvement to establish whether it has a pivotal mechanistic contribution or is rather an innocent bystander. Alternate measures of coronary atherosclerosis may be needed to elucidate contributors to atherosclerosis incidence or progression.

The studies I reference, above and this one, involved human subjects, and CVD incidence. The first compared data between healthy men (14,916 healthy participants in the Physicians’ Health Study), and men who had an MI (474 men with confirmed MI during the nine-year follow-up period). This second study compared 31 biomarkers (sICAM, among the 31) among patients whose CAC scores did not progress, versus those whose CAC scores progressed.

The study that started this thread analyzed the vascular endothelium of mice.They connect that to niacin in a roundabout way. Niacin elevates 4PY among humans. 4PY elevates sVCAM among humans. So they treat mice with 4PY, not niacin, then analyze the vascular endothelium of the mice.

Lastly, treatment with physiological levels of 4PY, but not its structural isomer 2PY, induced expression of VCAM-1 and leukocyte adherence to vascular endothelium in mice.

As Dr Bart observes: “Yes it’s correlation study in humans but the proof of concept study on mice is convincing.”

In the absence of human data, I read mouse studies, because they may predict human outcomes. But when contrary human data is presented, mouse data (to me) becomes useless.

As both the human studies conclude, it is sICAM, not sVCAM that is associated with CVD risk.

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#75

I think the reason this thread was started is to discuss whether it makes sense in a high Lp(a) context.

For someone with high Lp(a) there are still basically zero options and Lp(a) is a massive and different, independent from Apo B / LDL risk factor.

Is your comment meant for the context of high Apo B/LDL (for that I100% agree with your comment) or are you (also) talking about the context of someone with high Lp(a) (I’m not sure how to weigh things as Lp(a) is such a bad risk factor and if you have such a clear view on that trade-off I’d love to hear more)?

deaths due to heart disease did not go down
Is that for LDL lowering or HDL increasing trials or for Lp(a) lowering trials?

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Is anyone having significant side effects from Bempedoic Acid?
#76

Thanks @JuanDaw very much appreciate your analysis

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#77

The impact of Niacin on Lp(a) might also differ depending on what type of apolipoprotein phenotype a person has and/or LPA genetics:

  1. This might help stratify the risk/reward decision for someone with high Lp(a) further.

  2. we recommend genetic testing for patients with elevated Lp(a) and to consider Niacin therapy in a patient-to-patient case based on genetic profile

Lowering of lipoprotein(a) level under niacin treatment is dependent on apolipoprotein(a) phenotype

Abstract

Background

Lipoprotein(a) [Lp(a)] is a cardiovascular risk factor; in addition to being a low-density lipoprotein (LDL)-like particle, it contains highly heterogeneous apolipoprotein(a) [apo(a)]. No prior studies have evaluated extended-release (ER) niacin effect on Lp(a) level depending on apo(a) phenotype.

Methods

For this 24-week, prospective, open-label clinical trial we recruited 30 men (mean age 46.2 ± 7.5 years) with Lp(a) levels >20 mg/dL. No participant had previously received lipid lowering therapy, and started ER niacin 500 mg with stepwise dose increasing up to 1.5–2.0 g. Subjects were evaluated for Lp(a), lipids, high-sensitivity C-reactive protein, lipoprotein-associated phospholipase A2 (Lp-PLA2), and fibrinolytic markers (plasminogen activator inhibitor-1, tissue plasminogen activator/plasminogen activator inhibitor-1 complex, plasmin–antiplasmin complex). Patients were divided into two groups with major low- (LMW) or high-molecular weight (HMW) apo(a) isoforms determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of plasma under reducing conditions followed by immunoblotting.

Results

At baseline, groups were comparable in age, lipid, inflammatory and fibrinolytic biomarkers levels. There was a significant difference in baseline Lp(a) concentrations: 92 ± 29 mg/dL versus 54 ± 46 mg/dL in LMW and HMW apo(a) groups, respectively, p < 0.01. During the course of niacin treatment Lp(a) decreased by 28% (p < 0.003), Lp-PLA2 by 22% (p < 0.001), C-reactive protein by 24% (p = 0.07)*** in LMW apo(a) group***, whereas no changes in Lp(a) and biomarkers levels were obtained in HMW apo(a) group.

Conclusion

High-dose ER niacin declines elevated Lp(a) level in male subjects with low- but not high-molecular weight apo(a) phenotype.

https://www.sciencedirect.com/science/article/abs/pii/S1567568815000094#:~:text=Niacin%20is%20effective%20not%20only,7]%2C%20[8].

Niacin decreases Lpa(a) by 20%. However, there has been cases reported in the literature with 60-80% reduction in Lp(a) levels by Niacin alone based on Lp(a) isoform. The following case presents a patient with reduction of Lp(a) levels by 68% with Niacin.

62-year-old male with past medical history of CAD with elevated calcium score 254 and elevated Lp(a). Patient presented to the cardiologist office to establish care and at that time Lp(a) was 325.7 nmol/L not on any lipid reducing agents. Patient was started on high dose Rosuvastatin and 6 months later, repeat Lp(a) level was persistently high 313 nmol/L (3.9% reduction). Patient was started on Niacin 500 mg daily and 5 months later Lp(a) levels significantly reduced to 115 nmol/L (63% reduction).

Recent studies have shown that reduction of Lp(a) by Niacin could be related to Apolipoprotein(a) isoform size, which normally confers rate of Lp(a) anabolism and catabolism as well as structural and functional properties of Lp(a). However, apart from apo(a) isoform size, Niacin also binds to the LPA gene promoter region. Our patient underwent genetic testing, he had rs3798220 variant in LPA gene.Research has shown that the presence of such sequence variants near the promoter region, can affect niacin regulation and furthermore can explain the difference of Niacin effectivity among patients.
Conclusion

Based on these findings, we recommend genetic testing for patients with elevated Lp(a) and to consider Niacin therapy in a patient-to-patient case based on genetic profile.

https://www.jacc.org/doi/10.1016/S0735-1097(23)03757-9

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CVD and high Lp(a) levels
#78

$40/ 30 pills. Has to come from Poland? Wonder if they’ll ship to US.

I’ve been worried about megadosing the Niacin, cut back to 250 morning and night a few months ago. Now pretty much counting on the magic crystals (if cyclodextrins are actually crystals) Lol.

Guns, Bible, and Magic crystals.

#79

Seems it is a Polish startup and they have patented it if I understood correctly some articles I skimmed.

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#80

Perspective on how the potential cautions for the paper might (or might not) matter (from the context of people taking NAD or NAD precursors):

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#81

So Dr Sinclair and the paper above* in the context of Niacin have now pointed us to two different genetic variants that we might want to weigh in context of Niacin and/or NAD precursor supplementation.

Does anyone know how to easily check our status of those two?

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Is anyone having significant side effects from Bempedoic Acid?
Whole Genome Sequencing
#82

Another perspective for those trying to understand this stuff

NMN Probably Won't Make You Live Forever?

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#83

NMN has some specific uses, but is not beneficial for all. Based on my research the following people may find NMN useful:

  1. Overweight
  2. Sleep deprived
  3. Jet lagged

So, IMHO, most people here should not be taking NMN. Unfortunately I am all 3 above, so I’m in the sweet spot. :stuck_out_tongue:

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#84

Interesting. NAD+ also seems like a good thing to test and then make decisions depending on where one’s levels are in relation to one’s age group and overall percentile.

#85

Establishment medicine has been anti niacin for decades. Same old message.

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#86

Just a thought that occurred to me, but could it be that Niacin’s beneficial effects on lipoproteins is countered by its detrimental breakdown products (2PY & 4PY) and that’s why you see no overall effect on cardiovascular events and deaths ?

Also interestingly, in humans 2PY (and I’m assuming the same is true for 4PY) increases with age 2.6 fold

Blockquote

The mean plasma 2PY concentration in young (5-16 years old) healthy subjects was 0.39 +/- 0.22 micromol/l while in old healthy subjects (50-90 years old) it was approximately 2.6-fold higher. No gender differences was found in plasma 2PY concentration.

Blockquote

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#87

As an aside, Niacin was tested by @ConquerAging and it provided the worst epigenetic age tests he has had this year by a longshot. So, Niacin doesn’t seem all that it’s cracked up to be for longevity.

Use Bempedoic Acid, Ezetemibe or a statin instead.

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#88

Hey @ConquerAging , what do you think of this product?

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#89

This was true for higher dose niacin (500mg?) as I recall. He has since decreased the dosage (50mg?) to still get a NAD boost. Did I recall correctly?

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#90

As mentioned - I 100% agree with you on this for Apo B optimization (and don’t think there has been hardly any disagreement about that on this thread).

But @DeStrider - how do we use those medicines instead for Lp(a)? What to do in the context of high Lp(a) is or at least was the genesis/purpose of this thread.

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#91

Indeed Neo, thanks for keeping the discussion focused on my initial question. The focus is not on LDL or APOB but rather the focus is on Niacin or alternatives for Lp(a).

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