In this post, I link to and excerpt from Supplemental thiamine as a practical, potential way to prevent Alzheimer’s disease from commencing [PubMed Abstract] [Full-Text HTML] [Full-Text PDF]. Alzheimers Dement (N Y). 2021; 7(1): e12199. Published online 2021 Jul 28. doi: 10.1002/trc2.12199
There are 78 similar articles in PubMed Central.
The above article has been cited by Association Between Blood Biochemical Factors Contributing to Cognitive Decline and B Vitamins in Patients With Alzheimer’s Disease. [PubMed Abstract] [Full-Text HTML] [Full-Text PDF].
Qian T, Zhao L, Pan X, Sang S, Xu Y, Wang C, Zhong C, Fei G, Cheng X.
Front Nutr. 2022 Feb 21;9:823573. doi: 10.3389/fnut.2022.823573. eCollection 2022. PMID: 35265656 Free PMC article.
All that follows is from Supplemental thiamine as a practical, potential way to prevent Alzheimer’s disease from commencing:
It is better to attempt stopping Alzheimer’s disease (AD) before it starts than trying to cure it after it has developed. A cerebral scan showing deposition of either amyloid or tau identifies those elderly persons whose cognition is currently normal but who are at risk of subsequent cognitive loss that may develop into AD. Synaptic hypometabolism is usually present in such at-risk persons. Although inadequate adenosine triphosphate (ATP) may cause synaptic hypometabolism, that may not be the entire cause because, in fact, measurements in some of the at-risk persons have shown normal ATP levels. Thiamine deficiency is often seen in elderly, ambulatory persons in whom thiamine levels correlate with Mini-Mental State Examination scores. Thiamine deficiency has many consequences including hypometabolism, mitochondrial depression, oxidative stress, lactic acidosis and cerebral acidosis, amyloid deposition, tau deposition, synaptic dysfunction and abnormal neuro-transmission, astrocyte function, and blood brain barrier integrity, all of which are features of AD. Although the clinical benefits of administering supplementary thiamine to patients with AD or mild cognitive impairment have been mixed, it is more likely to succeed at preventing the onset of cognitive loss if administered at an earlier time, when the number of aberrant biochemical pathways is far fewer. Providing a thiamine supplement to elderly persons who still have normal cognition but who have deposition of either amyloid or tau, may prevent subsequent cognitive loss and eventual dementia. A clinical trial is needed to validate that possibility.
RESEARCH IN CONTEXT
Can one thiamine tablet a day keep Alzheimer’s away? This article argues that it may do so. The multiple elements that contribute to pathogenesis of Alzheimer’s dementia include mitochondrial depression, increased ROS, lactic acidosis and cerebral acidosis of the brain, cerebral depositions of amyloid and tau, synaptic dysfunction, disturbed neurotransmission, cognitive impairments, and disturbances affecting astrocytes, endothelial cells, and the blood brain barrier. Most of those elements of Alzheimer’s pathogenesis are addressed by thiamine which, if used at a time when a middle-aged person still has normal cognition, may prevent those components of pathogenesis from developing. In brief: it is easier to prevent Alzheimer’s than to try to reverse it after it has developed. The data supporting the prophylactic use of thiamine are robust. In order to validate its use, a clinical trial is advocated that would enroll persons aged 65 or older who have evidence of depositions of amyloid or tau in their brains, and randomly assign them to take, for as long as 5 years, either thiamine 100 mgs daily or a matched placebo tablet.
4 LEVELS OF THIAMINE IN PERSONS WITH NORMAL COGNITION CORRELATE WITH MINI-MENTAL STATE EXAMINATION SCORES
Blood thiamine and thiamine diphosphate levels were measured in 611 non-demented individuals by Lu et al.11 Thiamine diphosphate concentration showed a weakly positive correlation with Mini-Mental State Examination (MMSE) score (r = 0.1492, P < .001). They further analyzed the MMSE scores divided according to thiamine diphosphate level. Based on a cut-off level of 99.48 nmol/L (which was the lower value found by the authors to distinguish AD from controls), participants with a high thiamine diphosphate level performed better in Recall, as well as Attention and Calculation, than those with low levels. Particularly relevant in the present context are data from patients with MCI because they are closer to persons who have normal cognition. For example, Håglin et al. compared 32 MCI patients to 43 controls; plasma thiamine was 9.3 nmol/L in MCI, 18% lower than the 11.4 nmol/L in controls (P = .028); and thiamine monophosphate was 2.06 nmol/L in MCI, 43.9% lower than the 3.67 in controls (P = .001).12
The data provided in this paragraph and in the paragraph concerning thiamine in established AD, demonstrate the important part played by thiamine in the cerebral process underpinning cognitive loss.
5 PREVALENCE OF THIAMINE DEFICIENCY IN ELDERLY POPULATIONS
As regards the effect of age, older persons often have more co-morbidities and use more medications than younger ones but evidence suggests that neither of these affect thiamine levels,13 although there is some evidence that diuretics may deplete thiamine.14 The relevance of geographic locale and age is seen in a Belgian group of outpatients that had 10.5% of thiamine deficiency as assessed by the TPP TK method,15 while an English group, mean age 77.7, free from disease and taking no medication, had a thiamine level measured in RBC by HPLC that was 25.8% higher than in the healthy young controls having a mean age of 26 years, although it was 67.7% lower in a group of institutionalized elderlies of mean age 82.8 years.16 That study took the important precaution of excluding anyone who had used vitamin supplements in the past month or who drank > 7 units of alcohol per week. In New Zealand, Wilkinson et al. measured thiamine levels by HPLC in 221 ambulatory persons, mean age 76; their thiamine level was 32.1% lower than in the 100 healthy controls of mean age 41.5 years,13 and a subgroup of 39 with no active medical problems and taking no medications had a mean thiamine level that was almost identical to that in the 182 with comorbidities. For a list of nine commonly used medications, the thiamine pyrophosphate levels were similar between those taking and those not taking each medicine; unsurprisingly, the thiamine level for those not taking multivitamins was 24.2% lower than for those taking them. In brief: even using a more accurate laboratory method, elderly patients have been found to have either increased or decreased thiamine levels and as a result, it is uncertain what effect age has on thiamine levels.
6 THIAMINE DEFICIENCY CAUSES MITOCHONDRIAL DEPRESSION
Most of the enzyme deficiencies associated with thiamine deficiency and described in the text of this article, derive from mitochondrial function and, therefore, reflect its depressed function. That is also shown by studies of isolated mitochondria. Neuroblastoma cells grown in a thiamine deficient medium had at least 25% of mitochondria that were swollen and translucent by electron microscopy.17
7 CONSEQUENCES OF INCREASED REACTIVE OXYGEN SPECIES IN THIAMINE DEFICIENCY
Oxidative stress occurs if reactive oxygen species (ROS) reach abnormally high concentrations that impair redox-sensitive signaling pathways, causing calcium efflux from the endoplasmic reticulum (ER) and depressing mitochondrial function that could manifest as hypometabolism in the 18F-FDG scan. Thiamine’s importance for oxidative stress is because it is a cofactor for both α-ketoglutarate dehydrogenase and transketolase, thus reducing generation of NADH and limiting the actions of both the respiratory chain and antioxidant enzymes. . . . Thus, oxidative stress is a factor that might produce synaptic dysfunction in ways besides deficiency of ATP.
8 LACTIC ACIDOSIS AND KETOACIDOSIS IN THE BRAIN
Lactate can contribute up to ≈60% to oxidative brain metabolism, with glucose providing the rest. The neuronal monocarboxylate transporter is proton-coupled, therefore its increased use for lactate production may result in intracellular acidification. Reports of patients having both thiamine deficiency and cerebral acidosis are mostly from cases in the past when supplementary thiamine for individuals undergoing hemodialysis was unavailable and consequently, many of them had profound thiamine deficiency and became severely symptomatic. Administration of thiamine reduced their lactate levels and gave a statistically significant decrease in mortality.25 Thiamine deficiency, which is common in the general population especially in the elderly, is therefore a risk factor for cerebral acidosis.
9 THIAMINE AND THE CEREBRAL DEPOSITION OF AMYLOID
Thiamine deficiency also contributes to amyloid deposition.
10 THIAMINE AND CEREBRAL DEPOSITION OF TAU
Hyperphosphorylation of tau causing dystrophic neurites occurs when thiamine is deficient, and is lessened when that deficiency is corrected. Thus, thiamine-deficient mice had dystrophic neurites containing hyperphosphorylated tau30, 32 and the observations, already mentioned, by Sang et al., of mice with thiamine deficiency caused by TPK knockdown, showed that in addition to amyloid deposition they also had hyperphosphorylated tau.31 Zhang et al. showed that correcting thiamine deficiency reduced the numbers of cells containing hyperphosphorylated tau.4
11 THIAMINE AND SYNAPTIC DYSFUNCTION