Week 7: B Vitamins and brain health
Recording:
If you missed the class, or want to hear the lesson again, join Dr. Minoo as she covers the essentials of B vitamins and how they relate to brain health.
After class notes
Our Wednesday evening class got into quite the discussion on vision, particularly exercises which might help you to train your vision. Here is a video which was suggested. Remember to always check with your doctor before trying any new activities.
Recent news article about Niacin:
Just in time for our topic, a warning about too much niacin and the risk to the heart. You can read about it here.
B Vitamins and Brain Health
This class will review the 8 B vitamins, their role in our body, good dietary sources, groups at risk of deficiency, and evidence of the possible role of each of the B vitamins and brain health.
This video provides a glimpse of our lesson, highlighting the B vitamins and the role in our health. She reminds us to remember BiG YESS to stay up on these important vitamins.
Vitamins
Vitamins are a group of organic compounds which are essential for normal physiological functioning but which are not made by the body and therefore have to be consumed through food or supplements. Vitamins can help make our bones strong, improve immune function, regulate hormones, assist with cellular metabolism, and much more. There are two main types of vitamins: fat soluble and water soluble.
Fat-soluble vitamins are vitamins A, D, E and K. Fat-soluble vitamins need fat from foods to be adequately absorbed. They do not need to be consumed daily, and excess is stored in the liver and fatty tissues. While it is difficult to get too many fat-soluble vitamins from food sources, if you take high doses of fat-soluble vitamin pills, the excess can have harmful side effects.
Water soluble vitamins are the 8 different types of B vitamins, as well as Vitamin C. Water soluble vitamins aren’t stored in the body in significant amounts and must be replenished daily. If your body has an excess of water-soluble vitamins from taking high doses of supplements, it is excreted via the urine.
B vitamins
B vitamins are typically synthesized by plants. The exception to this is vitamin B12, which is synthesized by bacteria, and is typically consumed from animal products. All B vitamins help the body convert food (carbohydrates) into fuel (glucose), which the body uses for energy. B vitamins also help the body use fats and protein. B vitamins are also needed for red blood cell formation, eyes, digestion, nervous system, hormone and cholesterol production, cardiovascular health and brain health.
Homocysteine and B12, B6 and Folate (B9)
Homocysteine is an amino acid. Vitamins B12, B6 and B9 (folate) break down homocysteine to create other amino acids your body need:
● Methionine, an essential amino acid and antioxidant that synthesizes (creates) proteins.
● Cysteine, a nonessential amino acid synthesized from methionine that reduces inflammation, increases communication between immune cells and increases liver health.
Elevated homocysteine levels increase your risk of dementia, heart disease and stroke
Excess homocysteine may damage the lining of your arteries (blood vessels that carry oxygen-rich blood throughout your body). High levels of homocysteine can also lead to blood clots or blood vessel blockages. Artery damage or blood clots significantly raise your risk of heart attack.
Some conditions, disorders and other factors interfere with breaking down homocysteine and leave you with high homocysteine levels.
You may have too much homocysteine in your blood if you have:
● Deficiencies in vitamins B12, B6 or folate.
● Heart disease.
● Rare inherited diseases, such as homocystinuria (when your body can’t process methionine).
● Aging.
● Being male.
● Excessive alcohol use.
● Smoking.
Video: This excellent video is probably designed for professionals, but there is a lot of information on homocysteine, the link to vitamin B, and some practical information to discuss with your doctor.
This image depicts the factors influencing homocysteine in the body (left) and the possible affects (on the right). There is more information on this website.
What are the risks of high homocysteine levels?
Without treatment, elevated homocysteine levels can lead to severe health complications. Too much homocysteine increases your risk for:
● Blood clots.
● Dementia.
● Heart attack.
● Heart disease.
● Osteoporosis.
● Stroke.
What does the research say? The results are mixed.
(Dangour et al., 2015, Jerneren et al., 2015, van der Zwaluw et al., 2014, Zhang et al., 2017; Smith et al., 2018; Rutjes et al., 2018; Gil Martinez et al., 2022; Wang et al., 2022)
Observational studies have shown associations between elevated homocysteine levels and the incidence of both Alzheimer’s disease and dementia. Scientists think that elevated homocysteine levels may have a negative effect on the brain for a few reasons, including cerebrovascular ischemia leading to neuronal cell death and inhibition of methylation reactions.
However, evidence from RCTs suggest that vitamin B12 supplementation alone or with folic acid, vitamin B6, or both for 1 to 2 years does not improve cognitive function in older adults with or without dementia, mild cognitive impairment, or Alzheimer’s disease, even though supplementation lowers homocysteine levels. In addition, a review that included 14 studies with 27,882 participants, most of whom were age 60 years or older, compared folic acid, vitamin B12, vitamin B6, or a combination of these supplements to placebo. The supplements had little to no effect on global cognitive function when administered for up to 5 years and appeared to have no impact when administered for 5 to 10 years.
Some researchers have noted, however, that when researchers took baseline homocysteine and B-vitamin status into account, B-vitamin supplementation slowed cognitive decline in individuals at high risk of cognitive decline.
The findings of a recent systematic review published in February 2022 suggest that supplementation of B Complex vitamins, especially folic acid, may have a positive effect on delaying and preventing the risk of cognitive decline. In a recent meta-analysis published in April 2022, a total of 95 studies with 46,175 participants (25 RCTs, 20 cohort studies, and 50 cross-sectional studies) were included to investigate whether B vitamin supplementation can reduce the risk of cognitive decline and incident dementia. This meta-analysis included studies that measured cognitive function by using the Mini-Mental State Examination and the results suggest that B vitamins are associated with slowing cognitive decline, especially in populations who received early intervention and intervention of long duration. The analysis also found that higher intake of dietary folate, but not B12 or B6, is associated with a reduced risk of dementia in the non-dementia aged population.
There are many factors that affect our ability to get adequate nutrition (including B vitamins) as we age:
● Some vitamins and minerals, like Vitamin B12, are not absorbed as efficiently in older adults.
● Appetite may decrease as we get older, due to things like medication interactions, less physical activity, or depression.
● The ability to cook and prepare nutritious meals may be affected by conditions like poor vision or arthritis.
● Physical conditions like heart disease, diabetes, or cancer may change dietary needs.
● Chewing, swallowing, or digestive disorders may inhibit the ability to eat certain foods.
● Metabolism may slow, resulting in fewer calorie needs per day
Despite these changes, older adults still need adequate B vitamins daily for the brain and body to function properly. Choosing nutrient dense foods like fruits, vegetables, lean proteins, legumes, nuts, seeds, and whole grains is an optimal way to get the fuel we need. Let’s take a look at each of the B vitamins and the role that they play in our bodies and brain health.
Vitamin B6 (Pyridoxine)
Vitamin B6 in coenzyme forms performs a wide variety of functions in the body and is involved in more than 100 enzyme reactions, mostly with protein metabolism. Vitamin B6 also plays a role in cognitive development through the biosynthesis of neurotransmitters and in maintaining normal levels of homocysteine, an amino acid in the blood. Vitamin B6 is involved in gluconeogenesis and glycogenolysis, immune function, and hemoglobin formation.
Vitamin B6 is found naturally in many foods and is added to other foods, such as:
● Poultry, fish, and organ meats, which are all rich in vitamin B6
● Potatoes and other starchy vegetables, which are some of the major sources of vitamin B6 for Americans
● Fruit (other than citrus), which are also among the major sources of vitamin B6 for Americans
Certain groups of people are more at risk of vitamin B6 deficiency:
● People whose kidneys do not work properly, including people who are on kidney dialysis and those who have had a kidney transplant
● People with autoimmune disorders, which cause their immune system to mistakenly attack their own healthy tissues, for example, people with rheumatoid arthritis, celiac disease, Crohn’s disease, ulcerative colitis, or inflammatory bowel disease
● People with alcohol dependence
Foods high in B6 (source)
B6 and Cognitive function
(Riggs et al., 1996; Malouf et al., 2003)
(Riggs et al., 1996; Malouf et al., 2003)
Several studies have demonstrated an association between vitamin B6 and brain function in older adults. For example, an analysis of data from the Boston Normative Aging Study found associations between higher serum vitamin B6 concentrations and better memory test scores in 70 men aged 54–81 years.
However, a review of high quality research found no evidence that short-term vitamin B6 supplementation (for 5–12 weeks) improves cognitive function or mood in the two studies that the authors evaluated. The review did find some evidence that daily vitamin B6 supplements (20 mg) can affect biochemical indices of vitamin B6 status in healthy older men, but these changes had no overall impact on cognition.
More evidence is needed to determine whether vitamin B6 supplements might help prevent or treat cognitive decline in older adults.
Folate (B9)
Vitamin B9 plays a role in brain health, nerve function and the production of red blood cells. Specifically, your body needs folate to make DNA and other genetic material. Your body also needs folate for your cells to divide.
Folate is naturally present in:
● Beef liver
● Vegetables (especially asparagus, brussels sprouts, and dark green leafy vegetables such as spinach and mustard greens)
● Fruits and fruit juices (especially oranges and orange juice)
● Nuts, beans, and peas (such as peanuts, black-eyed peas, and kidney beans)
Folic acid is added to the following foods:
● Enriched bread, flour, cornmeal, pasta, and rice
● Fortified breakfast cereals
● Fortified corn masa flour (used to make corn tortillas and tamales, for example)
Most people in the United States get enough folate. However, certain groups are more at risk of folate deficiency:
● Teen girls age 14–18 years, women age 19–30 years, and non-Hispanic black women
● People with alcohol use disorder
● People with disorders that lower nutrient absorption (such as celiac disease and inflammatory bowel disease)
● People with an MTHFR gene variant
Food containing folate
Foods fortified with folic acid
Folate and Depression
(Huang, et al., 2018, Gougeon et al., 2016)
(Huang, et al., 2018, Gougeon et al., 2016)
Low folate status has been linked to depression and poor response to antidepressants in some, but not all, studies. The possible mechanisms are unclear but might be related to folate’s role in methylation in the brain, neurotransmitter synthesis, and homocysteine metabolism. However, other factors linked to depression, such as nutrition (low dietary intake) and alcohol use disorder, might also contribute to the observed association between low folate status and depression.
An analysis of 2005–2006 NHANES data found that higher serum concentrations of folate were associated with a lower prevalence of depression in 2,791 adults age 20 or older. The association was statistically significant in females, but not in males. However, another analysis showed no associations between folate intakes from both food and dietary supplements and depression among 1,368 healthy Canadians age 67–84 years.
Additional research is needed to fully understand the association between folate status and depression. Although limited evidence suggests that supplementation with certain forms and doses of folate might be a helpful adjuvant treatment for depressive disorders, more research is needed to confirm these findings.
Vitamin B12 (Cobalamin)
Vitamin B12 helps keep brain cells, nerve cells, and blood cells healthy. Vitamin B12 is required for the development, myelination, and function of the central nervous system; healthy red blood cell formation; and DNA synthesis. Vitamin B12 functions as a cofactor for an enzyme that catalyzes the conversion of homocysteine to the essential amino acid methionine. Methionine is required for the synthesis of DNA, RNA, proteins, and lipids.
Vitamin B12 is found in a wide variety of animal foods. Plant foods have no vitamin B12 unless they are fortified. Here are some foods with B12:
● Fish, meat, poultry, eggs, milk, and other dairy products contain vitamin B12.
● Clams, oysters, and beef liver are some of the best sources of vitamin B12.
● Some breakfast cereals, nutritional yeasts, and other food products are fortified with vitamin B12.
The body absorbs vitamin B12 from food in a two-step process. First, hydrochloric acid in the stomach separates vitamin B12 from the protein that it’s attached to. Second, the freed vitamin B12 then combines with a protein made by the stomach, called intrinsic factor, and the body absorbs them together.
Vitamin B12 in dietary supplements isn’t attached to protein and doesn’t require the first step. However, B12 in supplements does need to combine with intrinsic factor to be absorbed.
What happens if I don’t get enough vitamin B12?
If you have a vitamin B12 deficiency, you may feel tired or weak. You might also have pale skin, heart palpitations, loss of appetite, weight loss, and infertility. Your hands and feet might become numb or tingly, a sign of nerve problems. Other symptoms of vitamin B12 deficiency include problems with balance, depression, confusion, dementia, poor memory, and soreness of the mouth or tongue.
Certain groups of people may not get enough vitamin B12 or have trouble absorbing it:
● People with an autoimmune disease called atrophic gastritis might not absorb enough vitamin B12 because they make too little hydrochloric acid and intrinsic factor in their stomach.
● People with pernicious anemia do not make the intrinsic factor needed to absorb vitamin B12.
● People who have had some types of stomach or intestinal surgery might not make enough hydrochloric acid and intrinsic factor to absorb vitamin B12.
● People with disorders of the stomach and small intestine, such as celiac disease or Crohn’s disease, might not absorb enough vitamin B12.
● People who eat little or no animal foods, such as vegetarians and vegans, might not get enough vitamin B12 from their diets. Only animal foods have vitamin B12 naturally.
● Many older adults don’t have enough hydrochloric acid in their stomach to absorb the vitamin B12 that’s naturally present in food. People over 50 should get most of their vitamin B12 from fortified foods or dietary supplements because, in most cases, their bodies can absorb vitamin B12 from these sources.
B12 and dementia or cognitive function (O’Leary et al., 2012)
According to a systematic review of 35 prospective cohort studies in 14,325 participants aged 47 to 101 years followed for an average of 5.4 years, the evidence does not support a role for low vitamin B12 in the development of cognitive impairment or dementia. Additional clinical trials are needed to better understand the effects of vitamin B12 supplementation on cognitive function and cognitive decline.
Thiamin (B1)
According to a systematic review of 35 prospective cohort studies in 14,325 participants aged 47 to 101 years followed for an average of 5.4 years, the evidence does not support a role for low vitamin B12 in the development of cognitive impairment or dementia. Additional clinical trials are needed to better understand the effects of vitamin B12 supplementation on cognitive function and cognitive decline.
Thiamine (B1)
This vitamin plays a critical role in energy metabolism and, therefore, in the growth, development, and function of cells.
Thiamin is found naturally in many foods and is added to some fortified foods such as:
● Whole grains and fortified bread, cereal, pasta, and rice
● Meat (especially pork) and fish
● Legumes (such as black beans and soybeans), seeds, and nuts
Heating foods containing thiamine can reduce their thiamin content. For example, bread has less thiamin than its raw ingredients. Because thiamin is water soluble, a significant amount of the vitamin is lost when cooking water is thrown out. Processing also alters thiamine levels in foods; for example, unless white rice is enriched with thiamin, it has significantly less the amount of thiamin in brown rice.
Thiamine deficiency can cause loss of weight and appetite, confusion, memory loss, muscle weakness, and heart problems. A more common example of thiamin deficiency in the United States is Wernicke-Korsakoff syndrome, which mostly affects people with alcoholism. It causes tingling and numbness in the hands and feet, severe memory loss, disorientation, and confusion.
The following groups are among those at risk of thiamine deficiency.
● People living with alcohol dependence
● People living with HIV/AIDS
● People living with diabetes
● Older adults: possible reasons include overall low dietary intakes (may be due to factors mentioned above), a combination of chronic diseases, concomitant use of multiple medications, and low absorption of thiamin as a natural result of aging.
Thiamine and Alzheimer’s disease
(Gibson et al., 2013, Gibson et al., 1988, O’Rourke et al., 1990, Butterworth et al., 1990)
(Gibson et al., 2013, Gibson et al., 1988, O’Rourke et al., 1990, Butterworth et al., 1990)
According to animal studies, thiamin deficiency might play a role in the development of Alzheimer’s disease. For example, thiamin deficiency produces oxidative stress in neurons, death of neurons, loss of memory, plaque formation, and changes in glucose metabolism—these are all markers of Alzheimer’s disease. Autopsy studies have shown that transketolase and other thiamin-dependent enzymes have decreased activity in the brains of people with Alzheimer’s disease.
Few studies have assessed the prevalence of thiamin deficiency in people with Alzheimer’s disease. One of these studies found that 13% of 150 patients with cognitive impairment and acute-onset behavioral disturbances were considered thiamin deficient based on plasma levels. Larger, well-designed studies are needed to determine whether thiamin supplements are beneficial for Alzheimer’s disease.
Riboflavin (B2)
This vitamin is an essential component of two major coenzymes, flavin mononucleotide (FMN; also known as riboflavin-5’-phosphate) and flavin adenine dinucleotide (FAD). These coenzymes play major roles in energy production; cellular function, growth, and development; and metabolism of fats, drugs, and steroids.
B2 is found naturally in some foods and is added to many fortified foods, such as:
● Eggs, organ meats (such as kidneys and liver), lean meats, and milk
● Some vegetables (such as mushrooms and spinach)
● Fortified cereals, bread, and grain products
Most people in the United States get enough riboflavin from the foods they eat and deficiencies are very rare. However, certain groups of people are more likely than others to have trouble getting enough riboflavin:
● Athletes who are vegetarians (especially strict vegetarians who avoid dairy foods and eggs).
● Pregnant women and breastfeeding women and their babies.
● People who are vegan.
● People who do not eat dairy foods.
● People with a genetic disorder called riboflavin transporter deficiency.
Riboflavin and Migraines
(Schoenen et al., 1998; Thompson et al., 2017)
Riboflavin works to reduce oxidative stress and inflammation of nerves, which are contributors to migraine headaches. The vitamin is also needed for normal mitochondrial activities; migraines are sometimes caused by mitochondrial abnormalities in the brain. A few small-scale studies found some positive results with a modest reduction of frequency of migraines; however, more research is needed.
Niacin (B3)
Niacin helps turn the food you eat into the energy you need. Niacin is important for the development and function of the cells in your body. All tissues in the body convert absorbed niacin into its main metabolically active form, the coenzyme nicotinamide adenine dinucleotide (NAD). More than 400 enzymes require NAD to catalyze reactions in the body, which is more than for any other vitamin-derived coenzyme. NAD is also converted into another active form, the coenzyme nicotinamide adenine dinucleotide phosphate (NADP), in all tissues except skeletal muscle.
NAD and NADP are required in many metabolic processes in cells. NAD is primarily involved in catabolic reactions that transfer the potential energy in carbohydrates, fats, and proteins to adenosine triphosphate (ATP), the cell’s primary energy source.
Niacin is found naturally in many foods and is added to some foods, such as:
● Animal foods, such as poultry, beef, pork, and fish
● Some types of nuts, legumes, and grains
● Enriched and fortified foods, such as many breads and cereals
Most dietary niacin is in the form of nicotinic acid and nicotinamide, but some foods contain small amounts of NAD and NADP. The body also converts some tryptophan, an amino acid in protein, to NAD, so tryptophan is considered a dietary source of niacin.
Essential Amino Acid: Tryptophan
Tryptophan is an essential amino acid that cannot be produced by the human body and must be obtained through your diet. Tryptophan can be found in many protein-based foods and dietary proteins including meats, dairy, fruits, and seeds.
Tryptophan plays a role in the production of:
● Serotonin; a mood stabilizer
● Melatonin; which helps regulate sleep patterns
● Niacin or vitamin B3; converts food to energy at the cellular level
● Nicotinamide*
*Nicotinamide acts similarly to niacin but has a different molecular structure.
Niacin deficiency is very rare in the United States. However, some people are more likely than others to have trouble getting enough niacin:
● Undernourished people with AIDS, alcohol use disorder, anorexia, inflammatory bowel disease, or liver cirrhosis
● People whose diet has too little iron, riboflavin, or vitamin B6; these nutrients are needed to convert tryptophan to niacin
● People with Hartnup disease, a rare genetic disorder
● People with carcinoid syndrome, a condition in which slow-growing tumors develop in the gastrointestinal tract
Vitamin B3 has received a lot of attention recently because a derivative of B3 can be converted to a coenzyme called NAD+, which has been linked to anti-aging. Although NAD+ levels in the body naturally decrease with age, there is little evidence that NAD+ supplementation has anti-aging benefits.
Pantothenic acid (B5)
Vitamin B5 helps in making red blood cells, as well as sex and stress-related hormones produced in the adrenal glands. Vitamin B5 is also important in maintaining a healthy digestive tract, and it helps the body use other vitamins, particularly B2 (also called riboflavin). Vitamin B5 is also needed to make cholesterol, which is part of every cell.
B5 is naturally present in almost all foods and is also added to some foods, such as:
● Beef, poultry, seafood, and organ meats
● Eggs and milk
● Vegetables such as mushrooms (especially shiitakes), avocados, potatoes, and broccoli
● Whole grains, such as whole wheat, brown rice, and oats
● Peanuts, sunflower seeds, and chickpeas
Because some pantothenic acid is present in almost all foods, deficiency is rare except in people with severe malnutrition.
Biotin (B7)
Your body uses biotin to metabolize carbohydrates, fats, and protein. It also helps to regulate signals sent by cells and the activity of genes.
Many foods contain some biotin, including the following:
● Meat, fish, eggs, and organ meats (such as liver)
● Seeds and nuts
● Certain vegetables (such as sweet potatoes, spinach, and broccoli)
Biotin deficiency is very rare in the United States. However, certain groups of people may be at risk for deficiency:
● People with a rare genetic disorder called biotinidase deficiency
● People with alcohol dependence
● Pregnant and breastfeeding women
Biotin is often recommended for strengthening hair and nails, and it's found in many cosmetic products for hair and skin. However, the National Institutes of Health reports that there is insufficient data to support recommending supplementation.
Summary
Older adults need adequate B-vitamins daily for the brain and body to function properly. It’s best to get these nutrients from foods first, and supplement when necessary due to a nutrient deficiency. Choosing nutrient dense foods like fruits, vegetables, lean proteins, legumes, nuts, seeds, and whole grains is an optimal way to get the B vitamins we need. More research is needed to better understand the effect of each of the B vitamin status and/or supplementation on brain health. The best way to determine if you need a B vitamin supplement is to be evaluated by your physician.
References
NIH Consumer Fact Sheets
Thiamine (B1): https://ods.od.nih.gov/factsheets/Thiamin-Consumer/
Riboflavin (B2): https://ods.od.nih.gov/factsheets/Riboflavin-Consumer/
Niacin (B3): https://ods.od.nih.gov/factsheets/Niacin-Consumer/
Pantothenic acid (B5): https://ods.od.nih.gov/factsheets/PantothenicAcid-Consumer/
Vitamin B6: https://ods.od.nih.gov/factsheets/VitaminB6-Consumer/
Biotin (B7): https://ods.od.nih.gov/factsheets/Biotin-Consumer/
Folate or Folic Acid (B9): https://ods.od.nih.gov/factsheets/Folate-Consumer
Peer-reviewed research
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Tao L, Liu K, Chen S, Yu H, An Y, Wang Y, Zhang X, Wang Y, Qin Z, Xiao R. Dietary Intake of Riboflavin and Unsaturated Fatty Acid Can Improve the Multi-Domain Cognitive Function in Middle-Aged and Elderly Populations: A 2-Year Prospective Cohort Study. Front Aging Neurosci. 2019 Aug 29;11:226. doi: 10.3389/fnagi.2019.00226. PMID: 31555120; PMCID: PMC6727035.
Wang Z, Zhu W, Xing Y, Jia J, Tang Y. B vitamins and prevention of cognitive decline and incident dementia: a systematic review and meta-analysis. Nutr Rev. 2022 Mar 10;80(4):931-949. doi: 10.1093/nutrit/nuab057. PMID: 34432056.
Marashly ET, Bohlega SA. Riboflavin Has Neuroprotective Potential: Focus on Parkinson's Disease and Migraine. Front Neurol. 2017 Jul 20;8:333. doi: 10.3389/fneur.2017.00333. PMID: 28775706; PMCID: PMC5517396.
Smith AD, Refsum H, Bottiglieri T, Fenech M, Hooshmand B, McCaddon A, Miller JW, Rosenberg IH, Obeid R. Homocysteine and Dementia: An International Consensus Statement. J Alzheimers Dis. 2018;62(2):561-570. doi: 10.3233/JAD-171042. PMID: 29480200; PMCID: PMC5836397.
Gil Martínez V, Avedillo Salas A, Santander Ballestín S. Vitamin Supplementation and Dementia: A Systematic Review. Nutrients. 2022 Feb 28;14(5):1033. doi: 10.3390/nu14051033. PMID: 35268010; PMCID: PMC8912288.
Dangour AD, Allen E, Clarke R, Elbourne D, Fletcher AE, Letley L, et al. Effects of vitamin B-12 supplementation on neurologic and cognitive function in older people: A randomized controlled trial. Am J Clin Nutr 2015;102:639-47.
Jernerén F, Elshorbagy AK, Oulhaj A, Smith SM, Refsum H, Smith AD. Brain atrophy in cognitively impaired elderly: the importance of long-chain ω-3 fatty acids and B vitamin status in a randomized controlled trial. Am J Clin Nutr 2015;102:215-21.
van der Zwaluw NL, Dhonukshe-Rutten RA, van Wijngaarden JP, Brouwer-Brolsma EM, van de Rest O, In ’t Veld PH, et al. Results of 2-year vitamin B treatment on cognitive performance: Secondary data from an RCT. Neurology 2014;83:2158-66.
Zhang DM, Ye JX, Mu JS, Cui XP. Efficacy of vitamin B supplementation on cognition in elderly patients with cognitive-related diseases. J Geriatr Psychiatry Neurol 2017;30:50-9.
Rutjes AW, Denton DA, Di Nisio M, Chong LY, Abraham RP, Al-Assaf AS, et al. Vitamin and mineral supplementation for maintaining cognitive function in cognitively healthy people in mid and late life. Cochrane Database Syst Rev 2018;12:CD011906.
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Malouf R, Grimley Evans J. The effect of vitamin B6 on cognition. Cochrane Database Syst Rev 2003:CD004393.
Riggs KM, Spiro A, 3rd, Tucker K, Rush D. Relations of vitamin B-12, vitamin B-6, folate, and homocysteine to cognitive performance in the Normative Aging Study. Am J Clin Nutr 1996;63:306-14.
Malouf R, Grimley Evans J. The effect of vitamin B6 on cognition. Cochrane Database Syst Rev 2003:CD004393.
Huang X, Fan Y, Han X, et al. Association between serum vitamin levels and depression in U.S. adults 20 years or older based on National Health and Nutrition Examination Survey 2005-2006. Int J Environ Res Public Health 2018;15.
Gougeon L, Payette H, Morais JA, et al. Intakes of folate, vitamin B6 and B12 and risk of depression in community-dwelling older adults: the Quebec Longitudinal Study on Nutrition and Aging. Eur J Clin Nutr 2016;70:380-5.
Huang X, Fan Y, Han X, et al. Association between serum vitamin levels and depression in U.S. adults 20 years or older based on National Health and Nutrition Examination Survey 2005-2006. Int J Environ Res Public Health 2018;15.
Gougeon L, Payette H, Morais JA, et al. Intakes of folate, vitamin B6 and B12 and risk of depression in community-dwelling older adults: the Quebec Longitudinal Study on Nutrition and Aging. Eur J Clin Nutr 2016;70:380-5.
Gibson GE, Hirsch JA, Cirio RT, Jordan BD, Fonzetti P, Elder J. Abnormal thiamine-dependent processes in Alzheimer’s Disease. Lessons from diabetes. Mol Cell Neurosci 2013;55:17-25. [PubMed abstract]
Gibson GE, Sheu KF, Blass JP, Baker A, Carlson KC, Harding B, et al. Reduced activities of thiamine-dependent enzymes in the brains and peripheral tissues of patients with Alzheimer’s disease. Arch Neurol 1988;45:836-40. [PubMed abstract]
Butterworth RF, Besnard AM. Thiamine-dependent enzyme changes in temporal cortex of patients with Alzheimer’s disease. Metab Brain Dis 1990;5:179-84. [PubMed abstract]
O’Rourke NP, Bunker VW, Thomas AJ, Finglas PM, Bailey AL, Clayton BE. Thiamine Status of Healthy and Institutionalized Elderly Subjects: Analysis of Dietary Intake and Biochemical Indices. Age Ageing 1990;19:325-9. [PubMed abstract]
Schoenen J, Jacquy J, Lenaerts M. Effectiveness of high‐dose riboflavin in migraine prophylaxis A randomized controlled trial. Neurology. 1998 Feb 1;50(2):466-70.
Thompson DF, Saluja HS. Prophylaxis of migraine headaches with riboflavin: a systematic review. Journal of clinical pharmacy and therapeutics. 2017 Aug;42(4):394-403.