A Compromised Gut and Aging
Suppose we throw out the acetaldehyde-in-the-blood-and-brain hypothesis. Even if the liver can keep up with the load, the process of breaking down acetaldehyde into a harmless acetate itself will upset the NADH/NAD balance.
NAD (nicotinamide adenoid dinucleotide) is the most important co-enzyme in the body. Aldehyde dehydrogenase depends on it to break down toxic aldehydes. SIRT1 depends on it to keep cells from committing suicide. It is the key to glucose metabolism. Etc.
A shortage of NAD is a normal part of aging:
Once pancreatic β cells and neurons start having functional problems due to inadequate NAD biosynthesis, other peripheral tissues/organs would also be affected through insulin secretion and central metabolic regulation so that the metabolic robustness would gradually deteriorate over age at a systemic level. This cascade of robustness breakdown triggered by a decrease in systemic NAD biosynthesis might be the central process of aging. In this regard, aging is not a plethora of random events, but the process that occurs according to a functional hierarchy determined by the susceptibility (frailty) to systemic NAD biosynthesis.(24)
What’s the connection?
In a 1984 paper on the effects of systemic Candida overgrowth, Dr. Truss hypothesized that Candida could conceivably produce enough acetaldehyde to sneak through the normal deacetylation in the liver and cause the neurological damage that anecdotal evidence suggested it did. He showed the precise way acetaldehyde production caused a relative shortage of NAD—relative because NADH and NAD are converted from and to each other in the body, and acetaldehyde prevents NADH from converting back to NAD, thus causing a shortage of NAD. Dr. Truss still believed that any acetaldehyde that passed into the liver would be turned into a harmless acid. What he proposed was that some acetaldehyde latched onto proteins that didn’t go into the liver, thus escaping deacetylation and wreaking havoc elsewhere in the body.(25)
My question is: if acetaldehyde causes a shortage of NAD, and ALDH2 in the liver requires NAD to disarm acetaldehyde, wouldn’t a shortage of NAD lead to a decreased functionality of liver (and other) aldehyde dehydrogenases? My own experience with Candida symptoms and sudden alcohol intolerance, as well as anecdotal evidence elsewhere, is convincing enough evidence for me. (And now there’s evidence that the beta amyloid plaques in the brain originate in the liver (26). Is there a connection with acetaldehyde & NAD shortage there?)
It is well known that that list of factors that contribute to Alzheimer’s includes:
- Insulin resistance
- Heart disease
- Hypoxia (lack of oxygen to cells)
- Poor diet
- Cigarette smoke
- Environmental pollution
- Chronic inflammation
- Acetalcholine shortage
- Beta amyloid accumulation
- Tau microtubule breakdown
These are also related to Candida and acetaldehyde overload. The only factors that are not in the Alzheimer’s list that are on the Candida-exacertabing list are antibiotics and hormone overuse and any sugar/alcohol consumption (except for those last two items, the Mediterranean diet is also an anti-Candida diet).
If the Candida/Acetaldehyde/Alzheimer’s connection holds any water, it’s no wonder Alzheimer’s is more prevalent in developed countries. We’ve eliminated diseases connected with harmful bacteria—we pasteurize milk, inject meat with antibiotics (even before disease is present), add chlorine to our drinking water, take antibiotics at the slightest sneeze, and never replace the good bacteria that are killed off in the process. Our digestive tracts—our first line of defense against pathogens and our main metabolic organ—get depleted of the very diversity of flora that makes us develop and function normally.
Perhaps Alzheimer’s is the prize won at the end of a successful battle against all other diseases.
Can Moms Pass on Alzheimer’s in Birth/Infancy?
Studies show that people who have a mother with Alzheimer’s are more likely to “develop” Alzheimer’s than people who have a father with Alzheimer’s (27). And it’s the mother’s inherited phenotype that counts—the interaction of genes and environment; the whole immunity/metabolism package.
There is strong evidence that schizophrenia—another neurological disorder—is passed on by a mother with an infection at time of birth (28). The transfer of a mother’s adaptive immunity and metabolism (via gut population) happens at birth and during breast-feeding. If passing on a compromised system leads to schizophrenia, could it not also lead to Alzheimer’s (given a different gut imbalance)?
The thing that got me studying Candida as a possible culprit in my “brain fog” was the fact that, when I was under a lot of stress, my throat seemed constantly coated in gunk and I had to constantly clear my throat. Before finding similar complaints from people who purportedly suffered from Candida overgrowth, I chalked it off to a bad habit—a habit that I got from Mom who also constantly had to clear her throat—for as long as I could remember.
If Mom—who suffered from constant UTIs, yeast infections, allergies, constipation, and stress, and who bombarded her system with antibiotics to the degree that now nothing works for her UTIs—if by doing so she destroyed her adaptive immune system early enough to have passed the damage on to some of her children—could that account for my responses to stress and allergens?
Now I wonder—though I have no medical evidence—if I inherited my mother’s genetic response to certain environmental factors (diet, stress, allergens) that has resulted in a constant fight against an imbalance in gut flora, and consequently (if the NAD hypothesis is right), a steeper “aging” curve than others.
The hope I have in this is that if gut imbalance plays such a dominant role in brain aging, then there should be ways to correct the imbalance and, if not cure, at least slow the progression of mental malfunction.
The Niacinamide Experiment
Mom and I have been taking vitamin B3 supplements (in niacinamide form–which is the precursor to NAD) for four months now. One week into this regimen, Mom’s stool became normal. She who had suffered from terrible constipation all her life (as far as I can remember) now had (and continues to have) normal bowels.
Why? No other change was made in her diet.
One of the supposed benefits of niacinamide is that it is a potent antifungal against Candida. It is promoted in part for its ability to bring gut flora into balance.
If gut flora imbalance was the cause of Mom’s constipation, then perhaps the first effect of the vitamin was to bring balance to Mom’s intestines. That would explain the sudden normalization of her bowels.
Two weeks into this dietary change, Mom became so mellow that we started cutting back on her Seroquel (an antipsychotic used in neurodegenerative diseases like schizophrenia and Alzheimer’s). In two month’s time, Mom went from 150mg/day of Seroquel to 25mg. She has had tremendous cognitive improvement, but pending evidence of niacinamide’s effect on the brain, I would attribute that to the decrease in Seroquel.
We’ll see if Mom continues to improve over the next few months. That should lend credence to the effect of niacinamide on brain function, either directly or indirectly via the gut.
As for me, the main effect I see post-niacinamide is that I feel awake. I used to wonder if I was the only person who always felt never-quite-awake and consequently had trouble concentrating and remembering things. I went to a doctor with this complaint. The response was “everyone over 40 is tired.” Niacinamide gives me a caffeine high without the jitters, so I’m happy with it.
Did I have any intestinal/metabolic effects from niacinamide? One thing that happened was that I could tolerate alcohol with niacinamide. So I started enjoying “a moderate amount” again. Big mistake—you can’t feed and fight the monster at the same time. After a couple weeks of this, my gut and throat returned to their pre-niacinamide state of bloating and coating.
All this brings me to the conclusion that if niacinamide is effective for gut and brain function, other factors should not be ignored. Diet, not supplements, should be the main way to achieve balance in metabolism and immunity; the main way to stop the downstream effect of gut dysfunction on all other organs.
And that’s my speculation for 2011. Candida may end up being the red herring in the gut-brain axis, but it sure would be interesting to take a closer look at the gut’s function in Alzheimer’s.
What are your thoughts? Do you have an “outside the box” hypothesis of Alzheimer’s?
Your comments are welcome.
24. The NAD World: A New Systemic Regulatory Network for Metabolism and Aging – Sirt1, systemic NAD biosynthesis, and their importance. Shin-ichiro Imai, Cell Biochem Biophys, 2009 (53)2.
25. Metabolic Abnormalities in Patients with Chronic Candidiasis — The Acetaldehyde Hypothesis. Orian Truss M.D., Orthomolecular.org.
26. For Alzheimer’s, Amyloid Plaques Start in Liver, Not the Brain. Matt Krasucki, M.D., Dr. Chrono, March 2011.
27. Researchers ID Phenotype Tied to Maternal Alzheimer’s History. Doctor’s Lounge, November 22, 2010.
28. Maternal infection and schizophrenia: implications for prevention. Brown AS, Patterson PH., Schizophr Bull. 2011 Mar;37(2).
29. ALDH Activity Indicates Increased Tumorigenic Cells, But Not Cancer Stem Cells, in Prostate Cancer Cell Lines. CHUNYAN YU, ZHI YAO, JINLU DAI, et al, In Vivo, vol. 25, 2011.
30. High ALDH Activity Identifies Chemotherapy-Resistant Ewing’s Sarcoma Stem Cells That Retain Sensitivity to EWS-FLI1 Inhibition. Ola Awad, Jason T. Yustein, Preeti Shah, et. al., PLoS One 5(11), 2010.
31. The microbiota–gut–brain axis: learning from intestinal bacteria? Premysl Bercik, Gut, vol. 60, 2011.
32. The Relationship Between Intestinal Microbiota and the Central Nervous System in Normal Gastrointestinal Function and Disease. Stephen M. Collins, Premysl Bercik, GASTROENTEROLOGY 2009;136.