#21

Re NTFactor: I don’t usually jump this fast, and yes, many of the studies seem funded by NTFactor, but you’ve convinced me to give it a try. The risks seem low, and I could use some energy support. Thank you for bringing this to my attention. I’ll report back if my results are (to me) interesting.

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#22

Normalize hormones for life - which hormones? All of them? Are any more important than others? If you’re an older man, what is the optimal testosterone level?

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#23

Yeah, I hate that. To what degree are all those run of the mill vitamins and minerals necessary for the effectiveness of this supplement? I find it pretty odd that you need that specific mixture of so many bog standard vitamins and minerals for this to work. I can’t think of a reason why this would be so; ok, I can see, for example maybe some rare form of vitamin K2, maybe MK-9 being a key cofactor, so you include it, as that one unique addition. But why on earth do you need this gaggle of stuff you could get from a random multi - all of these are key for this to work? Very hard to make a case for that. Mostly it looks like padding to me. Maybe for someone who is deficient in all this on a horrible diet, ok, but then just get a multi.

This smells more like marketing, where the manufacturer throws in the kitchen sink, with the idea that you’ll find it harder to stop using the product - because if you have all these vitamins and minerals, you will no longer use your multi, or any dedicated single vitamin or mineral supplement, since you are already getting it in this one pill. And so you are now dependent on this pill for all your vitamins and minerals supplements, so you will find it harder to give up. Very underhanded.

And I hate this tactic, because I am very particular about how I supplement with vitamins and minerals. I want to control the forms of all these. I want to control the doses of all these. Some of these I don’t want, like vitamin E. For most I also want to control the timing and don’t want to take this particular vitamin with this other vitamin or mineral at the same time. And so on. All these jam packed higgedly piggedly into one compressed pill take away all control from me, and want to force me into some completely subpar supplementation. That is not why I carefully selected and curated my stack after years of research and optimization. No thanks.

This list of ingredients makes me very, very distrustful of this supplement. Maybe all this research they’ve done themselves and funded themselves is totally legit. But the way they are marketing this I find so unpalatable and underhanded, that I cannot get onboard with this. Pass. YMMV.

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#24

@DrFraser
Nice list, I agree with much of it, the rest I simply haven’t looked into.

Curious what evidence you’ve found that artificial sweeteners are a negative for dementia? Of course there are many types of artificial sweeteners and some I wouldn’t eat. I eat a lot of sucralose with the idea of it being relatively benign. I do worry about how it alters the microbiome but I haven’t found any data suggesting it increases risk of dementia. Frankly I’d cut them out if I had to and certainly if it were easy for me to but I rely on them for flavoring coffee and protein powder.

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#25

I think there is a role for exogenous melatonin.

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#26

Valacyclovir. Common side effects include headache and vomiting. Severe side effects may include kidney problems.

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#27

Why do you recommend Ezetimibe over Rosuvastatin?

#28

I think I agree with Vera-Health.ai on this one … probably messes up microbiome, which then worsens health in multiple domains.

The question of whether artificial sweeteners increase the risk of dementia is an area of ongoing research, and current evidence is not definitive. Some studies have suggested potential associations between the consumption of artificial sweeteners and cognitive decline, but these findings are not consistent across all research.

One hypothesis is that artificial sweeteners might affect the gut-brain axis, potentially influencing cognitive health. However, the mechanisms by which this could occur are not well understood, and more research is needed to establish any causal relationships.

It’s important to note that many studies on this topic are observational, which means they can identify associations but cannot prove causation. Factors such as overall diet, lifestyle, and genetic predispositions also play significant roles in the development of dementia, making it challenging to isolate the impact of artificial sweeteners alone.

In summary, while there is some evidence suggesting a possible link between artificial sweeteners and cognitive decline, the current body of research does not provide conclusive evidence that artificial sweeteners directly increase the risk of dementia. Further high-quality, longitudinal studies are needed to better understand this potential relationship.

#29

30 years in practice … yet haven’t seen a single patient in the ER due to side effects of valacyclovir. Certainly nothing, in general that is high enough grade to be more than an annoyance, except in rare circumstances.

@Rika_Qu If doing a statin, rosuvastatin is drug of choice, but it will low cholesterol in the brain to some degree (less than other statins). I prefer to use agents that don’t do this for people ApoE4’s, but if dong a statin, low dose rosuvastatin.

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#30

Hype? I don’t know, but a fair bit of published literature, and a fairly inexpensive product

My first impression is that it sounds like “hype” to me. I found no clinical trial data outside of some studies sponsored by NTFactor.

#31

You may want to consider Galantamine as well. My father uses it and it produces amazingly vivid dreams. It was originally approved by the FDA to treat dementia.

Galantamine alleviates the symptoms of dementia by improving cognition, global functioning, daily life activity, and behavior.

It is also thought to prevent Sarcopenia when paired with Metformin.

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#32

Btw. what is your opinion of the FINGER study/intervention? At this point there’s been quite a few years of follow up:

:top: https://fbhi.se/the-finger-study/

Meanwhile, on choline there’s this recent paper (caveat: Chinese), based on the UK Biobank data:

Association of dietary choline intake with incidence of dementia, Alzheimer disease, and mild cognitive impairment: a large population-based prospective cohort study

There’s a full text link within.

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#33

In regard to the finger study - it’s not dissimilar to the updated Lancet article I cite in my recommendations.
It’s interesting on Choline and Galantamine - I’m not convinced that this is disease modifying, but being on these likely delays the symptoms and makes things look better than they really are (drug free).
What I’m most interested in is identifying people at high risk 20 years before we’d expect them to get symptomatic AD - and have them on a number of items that are associated with decreased AD. Some of these will fall out and not prove to be useful once we have more data, but for most people, being on all these items and doing the investigations is without side effects (except the cost).
As I have an ApoE4 and both my parents have ApoE4’s and I have other family members homozygous ApoE4, this is a real area of interest that I’m refining in regard to treatment of myself, family and all my patients.
It’s also not just the ApoE4’s, folks with a strong family history of dementia probably should consider the same approach.
Please note, I’m not giving anyone medical advice, just discussing my protocol and will love to have this get updated as there is more literature.
@Jay I’ve looked through some of the research on NT Factor - I’m not overly sold on it, but there are many reasonable research pieces on this - Research – NTFactor
I think it is an item to consider.

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#34

“I (Nick Norwitz) have a personal reason to want to know a thing or two about Alzheimer’s disease, on account of the fact that I carry not one, but two copies of the major risk gene variant for Alzheimer’s disease, APOE4.”

:29.

B Ovatus, which makes lysophosphatidylcholine (LPC).

You can get LPC directly from krill oil, or fish roe. 6:41

Nick’s source paper is below.

https://www.cell.com/cell-metabolism/fulltext/S1550-4131(24)00402-9

Treatment with Bacteroides ovatus , or its associated metabolite lysophosphatidylcholine (LPC), significantly reduces Aβ load and ameliorates cognitive impairment. Mechanistically, LPC acts through the orphan receptor GPR119, inhibiting ACSL4 expression, thereby suppressing ferroptosis and ameliorating AD pathologies. Analysis of fecal and serum samples from individuals with AD also reveals diminished levels of Bacteroides and LPC. This study thus identifies a B.ovatus -triggered pathway regulating AD pathologies and indicates that the use of single gut microbiota, metabolite, or small molecule compound may complement current prevention and treatment approaches for AD.

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#35

Great list, actually very empowering. Question about artificial sweeteners, specifically xylitol. This is high on your list in this post. In a post below, you said that there are questions about this, needs more research.

Would like to have pointers to everything we know about xylitol / sugarless gum. How much is “OK?”

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#36

I used AI to pull the impact factors of the journals. Most do not have an impact factor, and the ones that do have a pretty low < 4. I also read through some of the studies starting from the most recent. After seeing that most of the articles are just reviews of other studies, and that those studies are frequently just case studies or in vitro studies (or worse, not even about NTFactor lipids), I gave up. The only compelling RCT didn’t even use NTFactor Lipids, but instead soy lecithin. NTFactor Lipids strikes me as a nothingburger, based on the huge page of studies here that really just serves to make you think they’ve got a lot of evidence, but I’ve gone through 13/64 and found absolutely nothing compelling. I can’t help but think this is just marketing to make it seem credible.

You’d probably be better off supplementing with soy lecithin or another lipids complex that actually states what is in the complex. Happy to change my mind if there’s specific studies in here, but so far this is definitely in the bucket of “not harmful, probably not helpful” for me.

Certainly, here’s the impact information for the journals associated with the listed papers:

  1. Applied Microbiology: This journal is an international, peer-reviewed, open access journal published quarterly by MDPI. As of January 2025, it is indexed within Scopus and EBSCO. The journal’s impact factor is not specified in the available sources.
  2. Functional Food Science: This peer-reviewed, open-access international journal serves as the journal of the Academic Society for Functional Foods and Bioactive Compounds. It has been indexed in Scopus since 2024, with a current CiteScore of 3.2 as of May 5, 2024.
  3. Townsend Letter: This publication is known for its focus on alternative and integrative medicine. It is not traditionally indexed in major scientific databases, and specific impact metrics are not readily available.
  4. International Journal of Translational Medicine: Specific impact metrics for this journal are not available in the provided sources.
  5. Bioactive Compounds in Health & Disease: This journal is peer-reviewed and open access, focusing on bioactive compounds and their impact on health and disease. Specific impact metrics are not provided in the available sources.
  6. Membranes: This is an international, peer-reviewed, open access journal published by MDPI. As of January 2025, it is indexed within Scopus and other databases. The journal’s impact factor is not specified in the available sources.
  7. Reproduction and Fertility: This journal focuses on reproductive biology and fertility research. Specific impact metrics are not provided in the available sources.
  8. International Journal of Clinical Medicine: This journal covers a broad range of clinical medicine topics. Specific impact metrics are not provided in the available sources.
  9. Journal of Orthomolecular Medicine: This journal focuses on nutritional and orthomolecular medicine. It is not traditionally indexed in major scientific databases, and specific impact metrics are not readily available.
  10. Functional Foods in Health and Disease: This journal is peer-reviewed and open access, focusing on functional foods and their role in health and disease. Specific impact metrics are not provided in the available sources.
  11. Biochimica et Biophysica Acta (BBA) - Biomembranes: This is a peer-reviewed scientific journal covering research on biomembranes. As of January 2025, it is indexed within major scientific databases. The journal’s impact factor is not specified in the available sources.
  12. Discoveries: This is a peer-reviewed, open access journal covering various scientific disciplines. Specific impact metrics are not provided in the available sources.
  13. Journal of the American Nutraceutical Association: This journal focuses on nutraceutical research. It is not traditionally indexed in major scientific databases, and specific impact metrics are not readily available.
  14. Integrative Medicine: A Clinician’s Journal: This journal focuses on integrative medicine practices. Specific impact metrics are not provided in the available sources.
  15. Alternative Therapies in Health and Medicine: This journal covers alternative and complementary medicine. Specific impact metrics are not provided in the available sources.
  16. Public Health Alert: This publication focuses on public health issues. It is not traditionally indexed in major scientific databases, and specific impact metrics are not readily available.
  17. Case Reports and Reviews: This journal publishes case reports and reviews across various medical disciplines. Specific impact metrics are not provided in the available sources.
  18. Journal of Healthcare & Prevention: This journal focuses on healthcare and preventive medicine. Specific impact metrics are not provided in the available sources.
  19. Journal of Pure and Applied Microbiology: This journal has achieved an Impact Factor of 0.7 as an Emerging Sources Citation Index (ESCI) journal.
  20. Journal of Functional Foods: This journal has an Impact Factor of 3.8 as of 2023.

Sfera A, Hazan S, Klein C, Zapata-Martin del Campo CM, Sasannia S, Anton JJ, Rahman L, Andronescu CV, Sfera DO, Kozakidis Z, Nicolson GL. Microbial translocation disorders: assigning an etiology to idiopathic illnesses. Applied Microbiology 2023; 3(1): 212-240

No reference to NTFactor lipids.

Nicolson, GL. Membrane Lipid Replacement—a functional approach to repairing cellular membranes, reducing symptoms, and restoring function. Functional Food Science 2022; 2(8): 198-204*

Review of membrane lipid replacement. Cites a study that uses soy lecithin and not NTFactor lipids. Interestingly, they claimed that they used NTFactor Lipids in the study, which is not mentioned anywhere in the study on menopausal women. Big red flag IMO.

Ash, M.E.; Settineri, R; Nicolson GL. Fatigue, Immunity and Inflammation: Their Resolution Using Natural Medicine. Townsend E Letter; June 4, 2022

Yet another review.

Nicolson GL, Settineri, R, Breeding PC. Recent Research on Membrane Lipid Replacement with NTFactor Lipids®: Enhancement of Nutrient Bioavailability and Reductions in Symptom Severities in Chemically Exposed Veterans Townsend Letter 2022

Another review, nothing new was really presented here.

Settineri R, Ji J, Shields ZP, Shirvani T, McLaren CE, Nicolson GL. The effects of Membrane Lipid Replacement with NTFactor® Lipids on increasing the bioavailability of three test nutrients. Bioactive Compounds in Health & Disease 2022, 5(5): 106-116.

In vitro study of combining NTFactor lipids with CoQ10, quercetin and curcumin in a Caco-2 epithelial cell permeability model. Not particularly interesting.

Nicolson, G.L.; Ferreira deMattos, G.; Ash, M.; Settineri, R.; Escribá, P.V. Fundamentals of Membrane Lipid Replacement: A Natural Medicine Approach to Repairing Cellular Membranes and Reducing Fatigue, Pain, and Other Symptoms While Restoring Function in Chronic Illnesses and Aging. Membranes 2021, 11, 944.

Yet another review.

Medica, A, Aitken,R, Nicolson, GL, Sheridan, AR, Swegen,A, De Luliis,G, Gibb,Z.Ferreira de Mattos G, Ash, ME, Settineri R. , Escriba, P. Glycerophospholipids protect stallion spermatozoa from oxidative damage in vitro. Reproductive and Fertility (2021) 2 199-209.

Yet another in vitro study.

Nicolson GL, Breeding PC. Membrane Lipid Replacement with NTFactor Lipids® reduces pain, fatigue, gastrointestinal and other symptoms in patients with peripheral pain. Townsend Letter2020; 449: 17-20.

Case study, weak evidence.

Nicolson GL, Settineri R. No Evidence of allergenic reactions to soy lecithin phospholipids used in Membrane Lipid Replacement Studies. Bioactive Compounds in Health and Disease 2021; 4(1): 9 – 13

Great, no allergic reactions.

Nicolson GL, Breeding PC. Settineri R, Ferreira de Mattos G. Aging and chronic illnesses: Membrane Lipid Replacement for restoring mitochondrial function and reducing fatigue, pain, and other symptoms in aged individuals. Bioactive Comp. Health Dis. 2020; 3(10): 194-203.

More case studies.

Hiroshi, A., Terauchi, M., Osaka, Y., Akiyoshi, M., Kato, and Miyasaka, N. Effect of soy lecithin on fatigue and menopausal symptoms in middle-aged woman: a randomized, double-blind, placebo-controlled study. Nutrition Journal (2018) 17:4. 00

This one is about soy lecithin, not NTFactor lipids.

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Menaquinone-7 - an interesting molecule to power up the mitochondria
#37

I’ve read and reread your list which is excellent.

As you know, I’ve ordered two Vibrant tests. I see you are also suggesting that one might consider testing for heavy metals/mold/PFAS. Do those results merely help motivate someone who is not making efforts to minimize those things, or are there potential treatments available that could make testing valuable for those who already take steps to avoid those toxins?

Also, you mentioned if one has apoe4, that starting late estrodial might be a ? As someone who started at aprox 56, I’m curious what late is?

And ooops, I took a Valium in order to do my whole body MRI the other day… figures I would hurt my health in hopes of helping my health :slight_smile:
(I had to do a head first MRI in the past and we almost had to call it off before it began!)

I’ll ask you some more detailed questions offline, but I thought these might be of more general interest to others.

TY!

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#38

Virtually all of them impact gut microbiome in a negative way.
Per AI review:
Xylitol, a sugar alcohol commonly used as a sweetener, has been studied for its potential effects on the gut microbiome. While xylitol is generally considered safe and is known for its dental health benefits, its impact on gut health is an area of ongoing research.

A recent review highlights the importance of understanding how non-nutritious dietary compounds, such as certain food additives, can affect the gut microbiota and potentially lead to adverse health effects1 . Although xylitol is not specifically mentioned in this review, the general concern about food additives suggests that xylitol could potentially influence gut microbiota composition.

The gut microbiome plays a crucial role in various aspects of human health, including immune function and metabolism2. Changes in the gut microbiota composition can affect health outcomes, such as the risk of developing allergies, weight management, and even the risk of colorectal cancer2
. Therefore, any substance that alters the gut microbiome, including xylitol, could potentially have health implications.

While specific studies on xylitol’s impact on the gut microbiome are limited, it is known that sugar alcohols can cause gastrointestinal symptoms like bloating and diarrhea in some individuals, which may be due to their fermentation by gut bacteria. This suggests that xylitol could alter the gut microbiota balance, although more research is needed to fully understand these effects.

In summary, while xylitol is generally safe and beneficial for dental health, its impact on the gut microbiome is not fully understood. Given the importance of the gut microbiome in overall health, further research is needed to determine the potential health risks associated with xylitol consumption.

@dicarlo2 I’m not convinced either way.

@DrRoss is a proponent - I’d love to have him put forth an argument for or against this product.

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#39

Great thread. I wish more doctors would think so holistically.

For this group I am wondering if you measure the plasma total β-amyloid (Aβ) Aβ42/Aβ40 ratio and if so how often? If so are you seeing any improvement of the Aβ42/Aβ40 ratio among ApoE4 patients taking rapamycin compared to APoE$ patients that are not taking rapamycin?

Total Aβ42/Aβ40 ratio in plasma predicts amyloid-PET status, independent of clinical AD diagnosis

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#40

Good question, yes, levels of p-tau and AB42/40 ratio are reasonable, and predictive in mid life on risk of dementia. I’m going to get mine and my wife’s done with our next blood draw.

They are expensive at Quest - think it was near $1K just for the AB42/40 ratio.

I just ordered these in Evexia with blood draw at LabCorp, each of these tests is $225, so $450 for both.

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