Thursday, September 22, 2022
HomeAlzheimerFolic Acid And Alzheimer's

Folic Acid And Alzheimer’s

Effect Of Serum Folate And Vitamin B

Cure in sight for Alzheimers?

In our Cox proportional hazards models, the association of plasma tHcy and dementia or AD risk was independent of B vitamin concentrations. However, even after adjustment for tHcy and all the study covariates, low folate concentrations were independently related to dementia and AD risk . The cumulative incidence of dementia by quartiles of folate concentrations is shown in . Compared with the top folate quartile, adjusted HRs for dementia were 2.22 for the bottom quartile, 1.83 for the lower second, and 1.16 for the third . The corresponding adjusted HRs for AD were 2.04 for the bottom folate quartile, 1.30 for the lower second, and 0.66 for the third . By contrast, adjusted HRs relating low vitamin B-12 concentrations to risk of developing dementia or AD were not statistically significant. Results did not change when the analyses were performed with B vitamins used as log-transformed continuous variables .

Population And Study Design

The current study data are derived from electronic health records held at Meuhedet Healthcare Services , which provides healthcare services with national coverage to 14% of the total population of Israel as detailed elsewhere.

A prospective birth cohort study design was applied . The eligible sample consisted of Israeli citizens from across the nation, aged 6075 years in 2013, without pre-existing dementia for at least 10 years before serum folate measurements began. Individuals with pre-existing dementia were excluded from this study. All study participants were selected by their physician to be screened for serum concentrations of folate and had a least one serum folate blood test reported.

Effect Of Folic Acid Supplementation On Levels Of Sam And Sam/sah

Folate is an essential vitamin that is involved in various biochemical reactions including the SAM metabolic cycle . There is an inverse relationship between folic acid and SAM concentrations throughout the one-carbon cycle. In this trial, daily use of folic acid supplements increased plasma SAM and SAM/SAH concentrations in elderly individuals with AD. SAM itself appears to be altered in some neurological disorders, including AD . For example, Trolin and coworkers treated patients with AD with vitamin B12, SAM, and folate for 6 months, causing a significant decrease in Hcy levels , while Bottiglieri et al. noted that oral SAM treatment for 4 to 8 months was associated with a significant increase in CSF SAM, indicating that oral SAM does cross the blood-brain barrier.

Read Also: Does Medicare Cover Alzheimer’s Testing

Quality Evaluation And Data Extraction

The Newcastle-Ottawa Scale was used to assess the quality and risk of bias . Studies with a NOS score of 6 or more were included for the meta-analysis. All discrepancies were resolved by discussion with a third author.

Two authors independently extracted the following data from all articles: first author’s name, publication year, country of survey, number of cases and controls, mean age of participants, the mean and standard deviation of folate or odds ratio or risk ratio or hazard ratio and their 95% confidence intervals .

The standardized mean difference is used as a summary statistic in meta-analysis when the studies all assess the same outcome, but measure it in a variety of ways. The SMD expresses the size of the intervention effect in each study relative to the between-participant variability in outcome measurements observed in that study . In the current study, SMD was used to calculate differences of mean folate levels between people who did and did not suffer from AD. SMD and corresponding 95% CIs of plasma/serum folate were calculated based on the sample size, mean, and SD. Median and range were also used to estimate mean and SD . 95% CI was transformed from SD through the formula as follows: 95% CI = mean ± 1.96 SD. The 25th and 75th percentiles were transformed to SD through the following formula: SD = Norm IQR = ×0.7413 . SMD < 0 represents a folate level that is lower in the AD group compared with that in the control group.

Is Folic Acid Bad For You

Scientists: B12, B16, and Folic Acid May Slow or Mitigate Alzheimers ...

Is Folic Acid for Alzheimers Safe?

Folic acid is safe and non toxic, and should not have any side effects in healthy people taking a suitable dosage. Large quantities of folic acid have, however, been linked to zinc and iron deficiencies. Increasing folic acid intake may be unsafe if youre taking antibiotics, especially medications containing Tetracycline as folic acid may affect the bodys ability to absorb this. On the whole, however, folic acid is very safe for otherwise healthy individuals.

Want to know whether folic acid is right for you? Where your ancestors really come from? How to lose weight faster? Or which exercises or supplements would help you reach your goals? Vitagene provides actionable intelligence about your ancestry, health traits, and helps you create healthy, lasting change in your life with a diet, exercise, and supplement recommendations based on your DNA, lifestyle, family history, and goals.

Don’t Miss: What Foods Help Prevent Dementia

It’s Possible That Folate Deficiency Could Make Neurons Vulnerable To Oxidative Damage Which In Turn Might Speed Up Brain Cell Aging And Damage

All Israeli women of childbearing age are advised by their personal physician or gynecologist to take a 400-microgram pill of folic acid daily.

The recommendation is even more urgent for women who hope to get pregnant or have just conceived, in which case they should take the pill until the end of the first trimester.

Low levels of the B vitamin in early pregnancy are believed to be the cause of more than half of babies born with neural tube disorders such as spina bifida a devastating condition in which there is incomplete closing of the spine and the membranes around the spinal cord during early development in pregnancy.

More than 80 countries use either mandatory or voluntary fortification of certain foods with folic acid to cut the rate of NTDs. Israel is one of those that recommend it strongly, but it does not require it by law.

Folic acid, which is converted by the body into folate, was discovered about 80 years ago and is on the World Health Organizations List of Essential Medicines. It is the 89th most commonly prescribed medication in the US, as it is in Israel

Folate, not produced by the human body, is necessary for producing DNA and RNA and metabolizing amino acids necessary for cell division.

The new study was carried out by University of Haifa psychiatric epidemiologist Dr. Anat Rotstein, who is currently a postdoctoral scholar at the Zuckerman Stem Leadership Program of the Icahn School of Medicine at Mount Sinai Medical Center in New York, and Prof.

Sufficient Intake Of Folate Reduces The Risk For Ad: Results From Cohort Studies

Eleven cohort studies published from 2005 to 2009 were included in the meta-analysis . Sample size ranged from 192 to 727. All studies were conducted in the USA.

Table 4. Summary of studies regarding the association between folate intake and the risk of AD in 11 cohort studies.

All the 11 cohort studies were included in the meta-analysis to examine the association between folate intake and AD in the elderly. The combined RR was 0.50 . As the recommended daily allowance of folate is 400 g, a daily intake of 400 g of folate was used as the cut-off to define the two subgroups . When the daily intake of folate was < 400 g, the combined RR and HR were 1.15 and 0.9 , respectively . When the daily intake of folate was equal to or higher than 400 g, the combined RR and HR were 0.44 and 0.76 , respectively . It indicated that sufficient folate intake is a protective factor for AD, which significantly reduces the risk for AD.

Figure 5. Meta-analysis for the associations between daily intake of folate and the risk of AD in the general population. Combined RR of AD with insufficient and sufficient folate intake, respectively Combined HR of AD with sufficient folate intake Funnel plot for publication bias of insufficient folate intake Funnel plot for publication bias of sufficient folate intake Funnel plot for publication bias of sufficient folate intake .

Read Also: Does Jack Nicholson Have Alzheimer’s

Folate Defiency/possible Deficiency Is Associated With The Risk For Ad: Results From Case

Fifteen case-control studies involving 971 AD patients and 1,059 controls were included in the meta-analysis . The sample size ranged from 27 to 181. Eight studies were conducted in European countries and seven studies were conducted in Asian countries.

Table 2. Summary of studies regarding the association between folate level and the risk of AD in 14 case-control studies.

The combined OR was 0.96 with 95% CI . According to the level of plasma/serum folate, all individuals were further divided into two subgroups, folate deficiency/possible deficiency group and normal group with folate level < 13.5 and 13.5 nmol/L, respectively . In the folate deficiency/possible deficiency group, the combined OR was 1.94 . However, the combined OR was 0.86 in the normal group . The above data indicated that folate deficiency/possible deficiency is correlated with AD risk. It suggested that folate deficiency/possible deficiency may increase the risk for AD.

Figure 3. Meta-analysis for the associations between folate levels and risk of AD. Combined folate OR of AD patients Combined OR in the folate deficiency/possible deficiency group and normal group Funnel plot for publication bias of AD vs. control Funnel plot for publication bias of the folate deficiency/possible deficiency group Funnel plot for publication bias of the normal folate group.

Measurement Of Biochemical Parameters

Study shows connection between vitamin deficiency and dementia

Serum folate and vitamin B12 levels were measured using an automated immunoassay analyzer . Plasma levels of Hcy, SAM, and SAH were analyzed via high-performance liquid chromatography , as described by Poirier et al. , and quantified relative to standards obtained from Sigma Chemical Co. . AD gene-related mRNAs were analyzed using real-time polymerase chain reaction . The interassay coefficients of variation ranged from 3 to 10%, within an appropriate range unlikely to induce statistical errors.

A40, A42, IL-6, and TNF in the patients’ blood were quantified with a standard ELISA kit . Briefly, frozen samples were sequentially extracted via a two-step extraction process . After sonication, the samples were centrifuged at 100,000g for 1h at 4°C, and the supernatant was decanted. The serum was then sonicated with the formic acid solution. A40, A42, IL-6, and TNF were quantified separately, using an ELISA kit specific for each amyloid fragment in accordance with the manufacturer’s instructions.

Don’t Miss: Does Terry Bradshaw Have Dementia

Assessment Of Peripheral Inflammatory Cytokine And Folate Levels

Blood samples were aseptically collected at the baseline, six-, and twelve-month assessments by venipuncture after a 10-to-12-h overnight fast. The concentrations of folate and vitamin B12 were determined on the same day using the AbbottArchitect-i2000SR automated chemiluminescence immunoassay system and its supporting kit . Additionally, the serum Hcy concentrations were determined with a Hitachi 7180 automatic biochemistry analyzer using the enzymatic conversion method. The kit was supplied by Beijing Strong Biotechnologies, Inc. . The serum levels of IL-6, TNF-, A-40, and A-42 were measured with a high-sensitivity sandwich ELISA kit . All measurements were performed in duplicate, and the average values were used in the statistical analyses.

Vitamin B12 And Folate In Relation To The Development Of Alzheimers Disease

  • Daniele Fricke

We read with interest the article by Wang et al. on the association of low serum levels of vitamin B12 and folate with Alzheimer’s disease occurrence. We think that it is difficult to establish a clinical diagnosis of AD in patients with deficiency of vitamin B12 or folate. ADin this situation could be hardly differentiated from other kinds of dementia particularly from dementia associated with B12 deficiency and vascular dementia.

Cobalamin is a co-factor in several metabolic pathways and its deficiency may be associated with dementia. The authors have controlled the hemoglobin levels. Nevertheless the dementia caused by vitamin B12 deficiency may not be accompanied by anemia. Dementia maybe the sole manifestation of cobalamin deficiency. The most important pathway in the nervous system that is adversely affected by cbalamin deficiency involves the conversion of homocysteine to methionine. Demyelination clearly plays a major role in the neuropathogensis of cobalamin deficiency and cognitive changes can occur as a result of central demyelination. Furthermore,it was recently showed that high levels of homocystein are associated with poor word recall in the elderly. High homocysteinemia can be caused by deficiencies of folate or vitamin B12.

We think that the relation between vitamin B12 and folate and the development of Alzheimer’s disease is still not yet established.


Also Check: Melatonin Side Effects In Elderly With Dementia

Study Quality And Data Extraction

Two reviewers independently assessed the included studies. The extracted data included the name of the first author, publication year, the ethnicity of samples, the number of subjects, gender distribution, mean age, mean follow-up duration, mean and SD of Hcy and folate levels for patients and controls, source and detection method used for Hcy and folate analyses, categories of plasma Hcy, and multivariable-adjusted effects . Different Hcy and folate concentration measurement units were converted to a standard format .

The Newcastle-Ottawa Scale was used to assess the quality of the included studies. The NOS contains three domains covering four, two, and three points. The total NOS score ranged from zero to nine stars, and six to nine points were considered high quality. All the selected articles scored six or more stars in this system .

All the included studies were approved by ethics committees and conducted according to the Code of Ethics of the World Medical Association . All the participants of the included studies provided written informed consent.

Folic Acid Supplementation Significantly Improved Cognitive Function By Regulating Peripheral Inflammatory Cytokines

How Can Folic Acid Impact Your Alzheimer

In this trial, folic acid supplementation beneficially affected global cognitive function, specifically participants performance on the Information and Digit Span tasks. The Information test is a valid indicator of long-term memory, whereas the Digit Span test examines attention/short-term memory,. Participants allocated to the folic acid supplementation group performed significantly better on the Information and Digit Span subtests than individuals allocated to the conventional-treatment group. Poor performance on memory tests is a main characteristic of the cognitive deficits in patients with MCI. Furthermore, memory decline has been associated with hippocampal lesions and AD. The hippocampus is located in the temporal lobe and plays important roles in the consolidation of information from short-term to long-term memory. Deterioration of the hippocampus precedes and leads to memory impairment in late adulthood,. In a recent clinical trial of individuals with mild cognitive impairment, treatment with B-vitamins appears to slow cognitive decline, total brain atrophy, and regional brain atrophy. Clinical trials to test this hypothesis are warranted.

You May Like: Is Nancy Pelosi Suffering From Dementia

Study Design And Participants

This study is a single-center randomized controlled trial with an intent-to-treat paradigm that seeks to investigate the effects of a twelve-month folic acid supplement intervention on cognition and peripheral inflammatory cytokine levels in older adults with MCI. Participants were enrolled between March 2013 and April 2013, based on the following criteria: 1) age 65+ 2) absence of terminal illness or mental disorders 3) not using any nutritional supplementation known to interfere with nutrition status, folate metabolism, or cognitive function in the three months prior to recruitment and 4) not living in a nursing home or being on a waiting list for a nursing home. Using random cluster sampling, six geographically convenient communities with a high proportion of older residents who were all native Chinese speakers were selected from the Binhai New District, Tianjin, China. Of the 4215 selected individuals, 2816 agreed to participate, but only 2317 individuals who met the inclusion criteria participated in the clinical, physical and neuropsychological examinations.

The study was conducted in compliance with the ethical principles of the Declaration of Helsinki and was approved by the medical ethics committee of Tianjin Medical University, China. Each subject provided written informed consent prior to study entry. This trial has been registered on May 4th 2013 with trial number ChiCTR-TRC-13003227 .

Effect Of Ad Diagnostic Criteria

To exclude that the association between plasma tHcy and AD resulted from inclusion of subjects who might have vascular dementia rather than AD, all analyses were repeated after the exclusion of 9 subjects with possible AD, who also had clinical or brain imaging evidence of relevant cerebrovascular disease . The HR for hyperhomocysteinemia remained essentially unchanged at 2.26 . The corresponding HR for each 1-SD increase in log-transformed baseline tHcy concentrations was 1.56 .

You May Like: What Is The Difference Between Old Age Forgetfulness And Dementia

Vitamin Deficiency Is Treatable And May Help Reverse Cognitive Decline

A January 2019 study in the International journal of molecular sciences emphasizes the importance of supplementing vitamin B12 , vitamin B9 , vitamin B6 in early stages of late-onset Alzheimers disease. This research lead by the Institute for Academic Medicine Houston Methodist Research Institute also noted that 20% of people over 70 and 40% of people over age 80 are are vitamin B12 deficient.

Researchers reporting in the Journal of the American Medical Association say Vitamin B12, folate, and sulfur amino acids may be modifiable risk factors for structural brain changes that precede clinical dementia and that that both vitamin B12 and total homocysteine concentrations may be related to accelerated aging of the brain.

A July 2020 study added to this by saying: recent advances in epigenetic research have enabled the development of epigenetic clocks, which have greatly enhanced our ability to investigate molecular processes that contribute to aging and age-related disease. These biomarkers offer the potential to measure the effect of environmental exposures linked to dynamic changes in DNA methylation, including nutrients, as factors in age-related disease. They also offer a compelling insight into how imbalances in the supply of nutrients, particularly B-vitamins may influence epigenetic age

There are many causes of Alzheimers Disease Vitamin deficiency is part of the puzzle


Most Popular