NutritionAntidepressants may lead to a decrease in niacin and NAD in patients with poor dietary intake

Fred
Posts: 370
Joined: Tue Aug 13, 2019 3:17 pm
Location: Sweden

Antidepressants may lead to a decrease in niacin and NAD in patients with poor dietary intake

Post by Fred » Sat Dec 14, 2019 3:39 am

This was published in The Journal Of Medical Hypotheses so it is a speculative paper but interesting nonetheless.

"Patients who develop nutritional deficiencies as a result of poor dietary intake, especially inadequate intake of proteins and vitamins, could potentially suffer from niacin deficiency and NAD depletion.

However, de novo synthesis of niacin and NAD in the kynurenine pathway of tryptophan metabolism may compensate for impaired dietary intake. The rate of synthesis of NAD and niacin from tryptophan oxidation depends on the induction of the enzyme indoleamine 2,3-dioxygenase (IDO) by pro-inflammatory cytokines such as interferon-gamma. Niacin synthesis is not limited by a decrease in tryptophan and excessive IDO activity may therefore lead to a decline in tryptophan levels.

Antidepressants have an anti-inflammatory effect, including reduction of interferon-gamma and therefore inhibition of IDO, the rate-limiting enzyme of the kynurenine pathway.

In theory, this could account for increased serotonin as more tryptophan becomes available for serotonin
synthesis. However, the downside may be that less NAD and niacin are synthesised downstream, which
could exacerbate common psychiatric problems.

It is our hypothesis that patients with poor dietary intake, who are treated with antidepressants, are at risk of developing niacin/NAD deficiency with possible development of associated neuropsychiatric symptoms.

We therefore propose that niacin supplementation be considered in patients with inadequate diets who are treated with antidepressants. We believe that if this does not happen, a subclinical niacin deficiency may result, which would be difficult to detect as it would cause the same symptoms of the original illness (e.g. depression). Niacin deficiency should be considered and ruled out in all patients with treatment-resistant depression, who have a poor response to antidepressants. This is potentially a costeffective and easy intervention, which could be examined in a randomized controlled trial."

https://sci-hub.se/10.1016/j.mehy.2014.12.017


Fred
Registered dietitian, Sweden.
NewLifeScience
Posts: 144
Joined: Thu Aug 22, 2019 4:17 pm

Re: Antidepressants may lead to a decrease in niacin and NAD in patients with poor dietary intake

Post by NewLifeScience » Sat Dec 14, 2019 4:47 pm

Fred wrote:
Sat Dec 14, 2019 3:39 am
This was published in The Journal Of Medical Hypotheses so it is a speculative paper but interesting nonetheless.

"Patients who develop nutritional deficiencies as a result of poor dietary intake, especially inadequate intake of proteins and vitamins, could potentially suffer from niacin deficiency and NAD depletion.

However, de novo synthesis of niacin and NAD in the kynurenine pathway of tryptophan metabolism may compensate for impaired dietary intake. The rate of synthesis of NAD and niacin from tryptophan oxidation depends on the induction of the enzyme indoleamine 2,3-dioxygenase (IDO) by pro-inflammatory cytokines such as interferon-gamma. Niacin synthesis is not limited by a decrease in tryptophan and excessive IDO activity may therefore lead to a decline in tryptophan levels.

Antidepressants have an anti-inflammatory effect, including reduction of interferon-gamma and therefore inhibition of IDO, the rate-limiting enzyme of the kynurenine pathway.

In theory, this could account for increased serotonin as more tryptophan becomes available for serotonin
synthesis. However, the downside may be that less NAD and niacin are synthesised downstream, which
could exacerbate common psychiatric problems.

It is our hypothesis that patients with poor dietary intake, who are treated with antidepressants, are at risk of developing niacin/NAD deficiency with possible development of associated neuropsychiatric symptoms.

We therefore propose that niacin supplementation be considered in patients with inadequate diets who are treated with antidepressants. We believe that if this does not happen, a subclinical niacin deficiency may result, which would be difficult to detect as it would cause the same symptoms of the original illness (e.g. depression). Niacin deficiency should be considered and ruled out in all patients with treatment-resistant depression, who have a poor response to antidepressants. This is potentially a costeffective and easy intervention, which could be examined in a randomized controlled trial."

https://sci-hub.se/10.1016/j.mehy.2014.12.017

Such a difficult syndrome to track. Very hard to measure the hormone levels related to depression (dopamine, serotonin, norepinephrine) and their interactions.

very good to know the potential pitfalls of long term use...
Taking:
Resveratrol 400mg since June 2019; 600mg since October 1
NMN Sublingual 250mg since june 2019 500mg since September 2019; 600mg since Dec 1, 2019
NAD+ Nasal, appx 100mg per day since September 2019; 200mg per day beginning mid November
Fred
Posts: 370
Joined: Tue Aug 13, 2019 3:17 pm
Location: Sweden

Re: Antidepressants may lead to a decrease in niacin and NAD in patients with poor dietary intake

Post by Fred » Sun Dec 15, 2019 1:19 am

Yes, we don't have any biomarkers for depression. No blood tests or brain scanning.

But the patient and family usually can tell when a person is depressed.
Fred
Registered dietitian, Sweden.
NewLifeScience
Posts: 144
Joined: Thu Aug 22, 2019 4:17 pm

Re: Antidepressants may lead to a decrease in niacin and NAD in patients with poor dietary intake

Post by NewLifeScience » Mon Dec 16, 2019 7:11 pm

Also, I would bet that untreated depression carries far worse consequences.
Taking:
Resveratrol 400mg since June 2019; 600mg since October 1
NMN Sublingual 250mg since june 2019 500mg since September 2019; 600mg since Dec 1, 2019
NAD+ Nasal, appx 100mg per day since September 2019; 200mg per day beginning mid November
Fred
Posts: 370
Joined: Tue Aug 13, 2019 3:17 pm
Location: Sweden

Re: Antidepressants may lead to a decrease in niacin and NAD in patients with poor dietary intake

Post by Fred » Tue Dec 17, 2019 10:19 am

NewLifeScience wrote:
Mon Dec 16, 2019 7:11 pm
Also, I would bet that untreated depression carries far worse consequences.
Yes. Death by suicide is one common outcome of non treated or treatment resistant depression.
Fred
Registered dietitian, Sweden.
canadahealthy
Posts: 110
Joined: Tue Aug 20, 2019 5:31 pm

Re: Antidepressants may lead to a decrease in niacin and NAD in patients with poor dietary intake

Post by canadahealthy » Tue Dec 17, 2019 7:31 pm

NewLifeScience wrote:
Mon Dec 16, 2019 7:11 pm
Also, I would bet that untreated depression carries far worse consequences.
I am thinking you mean more than just suicide... I know 2 people who were so obviously clinically depressed and decided to go the self-medication route... this is only anecdotal, but both eventually (read: after over a decade in both cases) developed severe bi-polar or psychosis. And neither recovered.

I take SSRIs and have for 30 years. I wish i was better educated about how difficult it would be to get off years later, but on the other hand, i needed something to survive, and that is what was available back then.

Funny thing is, if i went off them, (u have tried) I wouldn't get dangerously depressed, but i WOULD get extremely unmotivated and dull-witted. (Even depression is something one can get used to after a while) No one who knows me would ever suspect i was clinically depressed, since it is a hormone thing, not a mood thing.
Drdavid
Posts: 478
Joined: Thu Aug 15, 2019 9:59 am

Re: Antidepressants may lead to a decrease in niacin and NAD in patients with poor dietary intake

Post by Drdavid » Mon Dec 23, 2019 7:07 am

NewLifeScience wrote:
Sat Dec 14, 2019 4:47 pm
Fred wrote:
Sat Dec 14, 2019 3:39 am
This was published in The Journal Of Medical Hypotheses so it is a speculative paper but interesting nonetheless.

"Patients who develop nutritional deficiencies as a result of poor dietary intake, especially inadequate intake of proteins and vitamins, could potentially suffer from niacin deficiency and NAD depletion.

However, de novo synthesis of niacin and NAD in the kynurenine pathway of tryptophan metabolism may compensate for impaired dietary intake. The rate of synthesis of NAD and niacin from tryptophan oxidation depends on the induction of the enzyme indoleamine 2,3-dioxygenase (IDO) by pro-inflammatory cytokines such as interferon-gamma. Niacin synthesis is not limited by a decrease in tryptophan and excessive IDO activity may therefore lead to a decline in tryptophan levels.

Antidepressants have an anti-inflammatory effect, including reduction of interferon-gamma and therefore inhibition of IDO, the rate-limiting enzyme of the kynurenine pathway.

In theory, this could account for increased serotonin as more tryptophan becomes available for serotonin
synthesis. However, the downside may be that less NAD and niacin are synthesised downstream, which
could exacerbate common psychiatric problems.

It is our hypothesis that patients with poor dietary intake, who are treated with antidepressants, are at risk of developing niacin/NAD deficiency with possible development of associated neuropsychiatric symptoms.

We therefore propose that niacin supplementation be considered in patients with inadequate diets who are treated with antidepressants. We believe that if this does not happen, a subclinical niacin deficiency may result, which would be difficult to detect as it would cause the same symptoms of the original illness (e.g. depression). Niacin deficiency should be considered and ruled out in all patients with treatment-resistant depression, who have a poor response to antidepressants. This is potentially a costeffective and easy intervention, which could be examined in a randomized controlled trial."

https://sci-hub.se/10.1016/j.mehy.2014.12.017

Such a difficult syndrome to track. Very hard to measure the hormone levels related to depression (dopamine, serotonin, norepinephrine) and their interactions.

very good to know the potential pitfalls of long term use...
Here is an article to follow up with the one Fred posted regarding depression and NAD+

Version 1. F1000Res. 2018; 7: 132.
Published online 2018 Feb 1. doi: 10.12688/f1000research.12120.1
PMCID: PMC5795269
PMID: 29744033
NAD + biosynthesis, aging, and disease
Sean Johnson, Conceptualization, Writing – Original Draft Preparation, Writing – Review & Editing1 and Shin–ichiro Imai, Conceptualization, Funding Acquisition, Project Administration, Supervision, Writing – Original Draft Preparation, Writing – Review & Editinga,1

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5795269/

"Depression is a complex psychiatric disorder associated with a number of pathologies, including inflammation, synaptic dysfunction, metabolic syndrome, and cognitive deficit. Sirtuins have been shown to have a role in the development of depression 78. In the dentate gyrus region of the hippocampus, it has been shown that SIRT1 is decreased under conditions of chronic stress, which has been associated with depressive-like behaviors 79. Additionally, inhibition of SIRT1 by genetic or pharmacological methods has reproduced depressive behaviors. Activation of SIRT1 is able to lead to anti-depressive behaviors 79. However, it has been observed that SIRT1 regulates expression of monoamine oxidase A (MAO-A), which lowers serotonin and drives anxiety-like behaviors 80, indicating that a balance in SIRT1 expression/activity is important for mood disorders.

SIRT2 has also been reported in mood disorders. Hippocampal SIRT2 expression is decreased in chronic stress conditions 81. Pharmacological inhibition of SIRT2 recapitulates depressive behaviors. Adenovirus-mediated overexpression of SIRT2 produces anti-depressive behaviors, which were abolished when hippocampal neurogenesis was disrupted by X-irradiation 81."
Fred
Posts: 370
Joined: Tue Aug 13, 2019 3:17 pm
Location: Sweden

Re: Antidepressants may lead to a decrease in niacin and NAD in patients with poor dietary intake

Post by Fred » Mon Dec 23, 2019 10:19 am

Thank you David. Since resveratrol is a SIRT1 activator and was able to enhance CBF (cerebral blood flow) perhaps the dual supplementation of a NAD precursor and a STAC (sirtuin activating compound) like resveratrol would be more beneficial than either one.

This has to be tested in a clinical trial against placebo since any intervention that gives a patient hope can lower depression scores temporarily.
Fred
Registered dietitian, Sweden.
Drdavid
Posts: 478
Joined: Thu Aug 15, 2019 9:59 am

Re: Antidepressants may lead to a decrease in niacin and NAD in patients with poor dietary intake

Post by Drdavid » Tue Dec 24, 2019 7:58 am

I agree I think this would be an interesting research trial to be part of in the future. Your comment about placebo effect is true and many times overlooked in supplement research.
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