Vitamins to Prevent Dementia

The excitement about Vitamin E has cooled as a couple larger scale prospective randomized studies have failed to find the potential benefits alluded to by epidemiological and small scale studies.  Indeed, there is the possibility that vitamin E supplements might even cause a small increase in the death rate.  The research on folate looks very good for at least mild preventive benefit.  I recommend 800 mcg daily for everyone (50 cents/mo.). B-6 might have cardiac side-effects and more research needs to be done.  B-12 is probably a good idea for adults over age 50.  I recommend 500 mcg every other day (50 cents / mo).  I would hold off on vitamin E supplements until more information is available from the death rate debate.  I would also encourage individual vitamin supplements over a multivitamin, since vitamin A definitely causes on increased rate of death.  Vitamin D and K look important, too.  I recommend 2000 units vitamin D ($1.20 per month via internet, e.g. papanature.com) and vitamin K(1) and (2) ($6/month).  The latter two are great for muscle and bone strength, too.  See my Recommendations for Healthy Living.

Multivitamins Helps Elderly Cognition: In a DB PC study of 96 elderly over 65 years old and treated for 1 year, those on multivitamin improved on every test of cognition except long-term memory. Newfoundland; Effect of vitamin and trace-element supplementation on cognitive function in elderly subjects. Chandra RK. Nutrition 2001 Sep;17(9):709-12

Alzheimer's: MMSE Higher with Higher Vitamin K and D: In a study of 200 women with AD (mean age 80) and 100 age-matched community dwelling controls, BMI was significantly lower in women with more severe AD (MMSE<16). Metacarpal BMD ( P <.02) and serum concentrations of vitamin K 1 (P <.03) and 25(OH)D 3 (P <.001) were lower in severe AD than in mild AD (MMSE>15). Serum levels of intact PTH and Glu OC in severely demented patients were higher than those with mild dementia ( P <.001). Serum PTH concentration correlated negatively with serum 25(OH)D 3 level (P =.016). Serum concentration of vitamin K 1 correlated positively with that of 25(OH)D 3 (P <.001) and MMSE score (P <.001), and negatively with Glu OC (P <.001). Vitamin K deficiency and osteopenia in elderly women with Alzheimer's disease. Sato Y, Honda Y, et al. Arch Phys Med Rehabil. 2005 Mar;86(3):576-81.

Beta-Carotene, Vitamin C and E, Flavonoids Not Linked to Dementia in Study: In the prospective Honolulu-Asia Aging Study of Japanese-American men ages 45-68 at the start with up to 34 years follow-up, when data from 2,459 men found 235 developed dementia (102 cases of Alzheimer's disease, 38 cases of Alzheimer's disease with contributing cerebrovascular disease, and 44 cases of vascular dementia). After adjustment for sociodemographic and lifestyle factors, cardiovascular risk factors, other dietary constituents, and apolipoprotein E e4, intakes of beta-carotene, flavonoids, and vitamins E and C were not associated with the risk of dementia. Midlife dietary intake of antioxidants and risk of late-life incident dementia: the Honolulu-Asia Aging Study. Laurin D, Masaki KH, Foley DJ, White LR, Launer LJ., National Institute on Aging. Am J Epidemiol. 2004 May 15;159(10):959-67

Vitamin B-1 Thiamine No Help in Small Alzheimer's Study:  In a very small 15-patient 1-year DB PC study of a huge 3 mg/day dose of thiamine, no measurable impact on Alzheimer's was detected. A trial of thiamine in Alzheimer's disease. Nolan KA, Black RS, Sheu KF, Langberg J, Blass JP. Arch Neurol. 1991 Jan;48(1):81-3

Vitamin C 500mg and E 400 IU Decreased Alzheimer's: In a study of 633 elderly over 65 years old and disease-free who were then followed 4.3 years, of those with adequate vitamin intake data, none of 27 with vitamin E 400 IU and none of 23 with vitamin C 500 mg had Alzheimers (p<.04, p<.10) but multivitamin made no difference (E 30 IU, C 60mg). MC Morris, Rush U, Alz Dis Assoc Disord ’98 12(3):121-6.

Vitamin C and E Decreased Dementia but not for Alzheimer's: 3,300 Japanese-American men in Hawaii followed for 26 years found that vitamin E and C appear to limit the amount of damage after stroke. Also, they may protect against age-related changes. Dementia doubles every 5-7 years after 65. Vascular dementia second most common after Alzheimer's. At follow-up, there were 47 Alzheimer's, 35 vascular dementia, 50 mixed, 254 low cognitive but not dementia and 2,999 no mental decline at ages 71-93. Participants taking both vitamins E and C at least weekly developed 88% less vascular dementia and 69% less mixed but no difference in Alzheimer's. They had a 75% better chance of better mental performance. Long-term use better. Neurol 3/28/00 U Hawaii.

Vitamin A, C, E Didn't Decrease Alzheimer's: A four year prospective study of 980 elderly who were free of dementia at the start and of whom 242 developed dementia found no benefit to carotene, vitamins C or vitamin E either by supplement or in the diet. Antioxidant vitamin intake and risk of Alzheimer disease. Luchsinger JA, Tang MX, Shea S, Mayeux R. Arch Neurol. 2003 Feb;60(2):203-8. Columbia University.  Ed: This was a very large and well designed study.  It's failure to find any benefit is fairly strong evidence against these supplements.

Vitamin K and D and Calcium Reduced Fractures by 86% in Alzheimer’s: Deficiency of vitamins D and K1 causes reduced bone mineral density (BMD) in female AD patients. In a DB PC 2-year study of 200 AD patients, those who received 45 mg menatetrenone (K-2), 1000 IU ergocalciferol (vitamin D) and 600 mg calcium daily for 2 years had BMD in the second metacarpals increased by 2.3% in the treated group and decreased by 5.2% in the untreated group (P < 0.0001). Serum levels of vitamin K2 and 25-hydroxyvitamin D increased by 284.9% and 147.9%, respectively, in the treated group. Twenty-two patients in the untreated group sustained nonvertebral fractures (15 with hip fractures, two fractures each at the distal forearm and the proximal femur, each one fracture at the proximal humerus, ribs, and pelvis), and three fractures (2 with hip fractures, one fracture at the proximal femur) occurred among the treated patients (P = 0.0003; odds ratio = 7.5). Menatetrenone and vitamin D2 with calcium supplements prevent nonvertebral fracture in elderly women with Alzheimer's disease. Sato Y, Kanoko T, et al. Japan . Bone. 2005 Jan;36(1):61-8.

Vitamin E Not as Good as Donepezil: A small 60 patient Italian DB PC study of AD using 2000 IU of vitamin E vs. 10 mg/d of donepezil found donepezil much more effective. Donepezil versus vitamin E in Alzheimer's disease: Part 2: mild versus moderate-severe Alzheimer's disease. Onofrj M, Thomas A, Luciano AL, Iacono D, Di Rollo A, D'Andreamatteo G, Di Iorio A. Clin Neuropharmacol. 2002 Jul-Aug;25(4):207-15

Vitamin E and Selegiline Help Moderate-Severe AD Slow Progression: A DB PC trial of 341 patients with moderate to severe AD given selegiline, placebo, Vitamin E, or both found those on vitamin E progressed 25% less rapidly after 2 years, delaying deterioration by 230 days. Selegiline, which also has anti-ox properties, also slowed decline 215 days. But the combination slowed progression only 145 days. Sano M, et al: A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer’s disease. NEJM ’97 336:1216-22

Vitamin E and Western Diet vs. Japanese Diet Protective: Vascular dementia in 8,000 Japanese in Honolulu. Vitamin E had an odds ratio for developing vascular dementia of OR 0.32. Neurol 7/99

Vitamin E + C in Food Found Protective: Two prospective non-randomized JAMA 6/26/02 studies report dietary but not supplement E were protective. A Chicago study of 7 years covering 819 adults at Rush found a 67% decrease in the highest vs. the lowest vitamin E quintile. A nine year Dutch study of over 5000 elderly over 55 years of age found vitamins E + C, flavonoids, beta-carotene in food protective.

Vitamin E Associated with Less Dementia in Rotterdam Study: An prospective epidemiologic study of 5,395 older adults. A high dietary intake of vitamins C and E was associated with a somewhat lower risk of dementia--OR = 0.82. Dietary intake of antioxidants and risk of Alzheimer disease. Engelhart MJ, Geerlings MI, Ruitenberg A, van Swieten JC, Hofman A, Witteman JC, Breteler MM. JAMA. 2002 Jun 26;287(24):3223-9

Vitamin E 400 IU Slows Cognitive Decline: 2,889 elderly with cognitive testing and 3 years follow-up found that those with the highest vitamin E intake from food or supplements had smallest decline, 36% less than those with the smallest intakes (7 IU. 18-22 IU recommended). Vit C and A were not associated with cognitive decline. Morris, Arch Neuro 02;59:1125, Rush

Vitamin E Meta-Analysis Found Only One Study: A meta-analysis in 2000 found only one study meeting inclusion criteria. That study of 341 elderly found fewer vitamin E supplemented elderly dying or institutionalized or deteriorating, but there were 3 times as many falls with vitamin E. Reviewers said not enough evidence to say of benefit. Vitamin E for Alzheimer's disease. Tabet N, Birks J, Grimley Evans J. Maudsley. Cochrane Database Syst Rev. 2000;(4):CD002854

B-6 Helped Elderly Memory in Very Small Study: A DB PC study of 76 men 70-79 years of age treated for 3 month with placebo or 10 mg/day of vitamin B-6 found no impact on mood. However, mental performance improved. Vitamin B-6 supplementation in elderly men: effects on mood, memory, performance and mental effort. Deijen JB, van der Beek EJ, Orlebeke JF, van den Berg H.

B6-12 May Help, Homocysteine Increased in AD: A University of Oxford study found high blood homocysteine, which is associated with heart disease, was also more common in 76 Alzheimer’s patients. Robert Clarke Arch Neurol. 1/99. The upper tertile (third) had at least a 2-fold increase AD (highest tertile to lowest RR 4.5). Inverse correlation serum folate (lowest tertile to highest = RR 3.3) and B12 (lowest tertile to highest RR 4.3) and AD (Clarke Arch Neurol 11/98 55:1449-55). Homocysteine increases with age, in male, with smoking, and with creatinine.  Decreases in these vitamins may be related to hyperhomocysteinemia because they are required for metabolism of it. Homocysteine has direct neurotoxic effects. Polyvitamin treatment with B6, B12 and folate is effective in lowering homocysteine. Cereals in US fortified with folic acid since 1/1/98 to prevent neural tube defects but not enough to affect homocysteine. Arch Neurol 11/98 55:1407

Low Folate Linked to Cognitive Decline: Elevated homocysteine blood level is a risk factor for cognitive decline and Alzheimer disease. In a 7-year follow-up study of 499 high-functioning community-dwelling elderly ages 70-79, after adjusting for multiple covariates, including homocysteine, B-6, and B-12 levels, those in the bottom quartile of folate had a 1.6 fold increased risk (P =0.04) of being in the worst quartile of 7-year cognitive decline. Low folate levels largely accounted for a trend towards greater cognitive decline with elevated homocysteine level. The risk of developing cognitive decline might be reduced through dietary folate intake. Homocysteine versus the vitamins folate, B6, and B12 as predictors of cognitive function and decline in older high-functioning adults: MacArthur Studies of Successful Aging. Kado DM, Karlamangla AS, et al. University of California Los Angeles. Am J Med. 2005 Feb;118(2):161-7.

Folate Low in Dementia Study: In a study of 55 nondemented elderly, 81 mildly cognitively impaired, and 92 demented adults with AD (n = 74) or VaD (n = 18), those in the lowest folate tertile had a higher rate of mild cognitive impairment (OR: 3.1) and dementia (3.8). Hyperhomocysteinemia was associated with dementia (OR: 4.3) and AD (OR: 3.7). Homocysteine, folate, and vitamin B-12 in mild cognitive impairment, Alzheimer disease, and vascular dementia. Quadri P, Fragiacomo C, et al. Mendrisio, Switzerland. Am J Clin Nutr. 2004 Jul;80(1):114-22

Folate Decreases Atrophy: Previous studies suggested that low concentrations of folate in the blood are related to poor cognitive function, dementia, and Alzheimer disease-related neurodegeneration of the brain. Nutrients, lipoproteins, and nutritional markers were measured in the blood of 30 participants in the Nun Study from one convent who later died when they were 78-101 y old (mean: 91 y). At autopsy, several neuropathologic indicators of Alzheimer disease were determined, including the degree of atrophy of 3 lobes of the neocortex (frontal, temporal, and parietal) and the number of neocortical Alzheimer disease lesions (ie, senile plaques and neurofibrillary tangles) as assessed by a neuropathologist. The correlation between serum folate and the severity of atrophy of the neocortex was -0.40 (P = 0.03). Among a subset of 15 participants with significant numbers of Alzheimer disease lesions in the neocortex, the correlation between folate and atrophy was -0.80 (P = 0.0006). Atrophy may be specific to low folate because none of the 18 other nutrients, lipoproteins, or nutritional markers measured in the blood had significant negative correlations with atrophy. Snowdon DA, U Kentucky. Am J Clin Nutr 2000 Apr;71(4):993-8

Folate Deficiency Common in Spanish Elderly, Linked to Low MMSE: Functional and psychic deterioration in elderly people may be aggravated by folate deficiency. Ortega RM, Manas LR, et al. J Nutr 1996 Aug;126(8):1992-9: 177 elderly Spanish people. Folate deficiency is common in the Spanish population. In this study, 48.6% of the elderly subjects had folate intakes below recommended values (200 microg/day), 34.9% had serum concentrations < 14 nmol/L and 6.6% had <360 nmol/L erythrocyte folate. Activities of daily living were significantly better (indicating greater independence and capacity) when folate intake and serum or erythrocyte folate concentrations were adequate (i.e., folate intake no less than recommended, > or = 14 nmol/L serum folate or > or = 360 nmol/L erythrocyte folate). Subjects with adequate Mini-Mental State Exam results (> or = 28 points) had serum and erythrocyte folate concentrations significantly higher than those with less adequate results (<28 points).

Folate Helps Prevent Alzheimer's: From the Baltimore Longitudinal Study of Aging, 579 over 59 without Alzheimer's disease were followed for nine years.  Foods rich in folate include oranges, bananas, leafy green vegetables, asparagus, broccoli, liver, and many types of beans and peas, as well as fortified bread. During follow-up, 57 developed Alzheimer's disease. Those with a higher dietary intake of folate had a 60% lower rate of the disease compared to the lowest quartile. Older adults whose total folate intake (diet and supplement) equaled or exceeded the 400 microgram RDA reduced their chances of developing Alzheimer's disease by 55 percent. No association was seen between intakes of vitamin C, carotenoids, or vitamin B-12. Vitamin E and B-6 had no effect when controlling for folate. Maria Corrada, et al. University of California, Irvine. WebMD 8/15/05

Folate and B-12 Low in AD and FTD: In a study of AD (n=152) and FTD (n=28) patients, significantly negative correlations between levels of serum vitamin B12 and red cell folate and the degree of cognitive deterioration were found. In FTD patients, levels of vitamin B12 were also negatively correlated with both hallucinations (p=0.022) and diurnal rhythm disturbances (p=0.036). Correlations between cognitive, behavioural and psychological findings and levels of vitamin B12 and folate in patients with dementia. Engelborghs S, Vloeberghs E, et al. Antwerp, Belgium. Int J Geriatr Psychiatry. 2004 Apr;19(4):365-70

Folic Acid Without B-12 Dangerous in Elderly: In a study of 1,300 adults over 59, 23% had low B-12 levels. Within this group, those with the highest folic acid levels were 2.6 times as likely to show cognitive impairment as those with less as well as 3.1 times as common to have anemia. However, for those with normal B-12 levels, folic acid appeared to protect against cognitive impairment and had no relationship to anemia. Morris MS, et al. Tufts University. Amer J Clin Nutr 1/07.

Folic Acid Helped Prevent: In a DB PC study of 818 Dutch adults ages 50-70, those taking folic acid 800 mcg daily for three years had significantly better memories and were faster at processing information, similar to adults almost five years younger. Taking folic acid also led to a significant reduction in levels of homocysteine. Jane Durga, fet al. University of Wageningen, Netherlands. Lancet 1/19/07.

Folate Helps Prevent: From the Baltimore Longitudinal Study of Aging, 579 over 59 without Alzheimer's disease were followed for nine years.  Foods rich in folate include oranges, bananas, leafy green vegetables, asparagus, broccoli, liver, and many types of beans and peas, as well as fortified bread. During follow-up, 57 developed Alzheimer's disease. Those with a higher dietary intake of folate had a 60% lower rate of the disease compared to the lowest quartile. Older adults whose total folate intake (diet and supplement) equaled or exceeded the 400 microgram RDA reduced their chances of developing Alzheimer's disease by 55 percent. No association was seen between intakes of vitamin C, carotenoids, or vitamin B-12. Vitamin E and B-6 had no effect when controlling for folate. Maria Corrada, et al. University of California, Irvine. WebMD 8/15/05

Folic Acid: Alzheimer, Parkinson’s Affected by Folate: Recent epidemiological and experimental studies have linked folate deficiency and resultant increased homocysteine levels with several neurodegenerative conditions, including stroke, Alzheimer's disease and Parkinson's disease. Moreover, genetic and clinical data suggest roles for folate and homocysteine in the pathogenesis of psychiatric disorders. NIH. Folate and homocysteine metabolism in neural plasticity and neurodegenerative disorders. Mattson MP, Shea TB. Trends Neurosci 2003 Mar;26(3):137-46 

Folic Acid: Homocysteine Increased; B6-12 and Folate May Help: U Oxford found high blood homocysteine, which is associated with heart disease, was also more common in 76 Alzheimer’s patients. Robert Clarke Arch Neurol. 1/99. The upper tertile (upper third) in homocysteine had at least a 2-fold increase in Alzheimers (highest tertile to lowest RR 4.5). There were inverse correlations for serum folate (lowest tertile to highest = RR 3.3) and B12 (lowest tertile to highest RR 4.3) and Alzheimers (Clarke Arch Neurol 11/98 55:1449-55). Homocysteine increased with age, in male, with smoking, and with creatinine.  The decrease in these vitamins may be related to hyperhomocysteinemia because they are required for metabolizing it. Homocysteine has a direct neurotoxic effect. Polyvitamin treatment with B6, B12 and folate was effective in lowering homocysteine. Cereals in US have been fortified with folic acid since 1/1/98 to prevent neural tube defects but not enough to affect homocysteine. Arch Neurol 11/98 55:1407. 

Folate 2-5 mg and Similar Amount B-12 Recommended: Alzheimer's is up 300%, stroke 500%, and vascular dementia 500% in those in the upper quartile of the normal range of homocysteine in a case controlled study of 280 patients. Recommendation only speculative and by Tel Aviv researcher Gorzcyn on Science Daily 10/4/02. McIlroy, Univ Belfast, J Amer Heart Assoc 10/02. Ed: I favor folate 1 mg and B-12 500 mcg/day, i.e., not as much as this author, but more than the U.S. government's 100% Daily Value.

Mild B-12 Deficiency Common: Study of elderly Dutch found 23% of free-living 74-80-year-olds had mild deficiency. Only 1 of 25 with deficiency had an inadequate intake. 31% of elderly have atropic gastritis in U.S. and Netherlands. But this explained only 25% of the deficiency cases. In the U.S., 30-40% seniors take supplements and 14% in Netherlands. Article says higher B-12 in US cereal may be reason fewer in US have high methylmalonic acid levels (MMA). Only 8% with mild deficiency had anemia. Van Asselt, Am J Clin Nutr ’98;68:328-34 and editorial.

B-12 and Vitamin C deficiency More Common: 260 noninstitutional adults not on meds over 60 were studied. Those low on B-12 and/or vitamin C did worse on Halstead-Reitan or Wechsler Memory Test. Low folate or B-12 worse on Halstead-R. JAMA ’83;249:2917

Zinc May Help: Although zinc is found in plaques, 30 mg/day supplement to six patients increased membrane viscosity and four of the patients followed for 12 months had cognitive improvement. It may be premature to conclude that zinc is harmful. Potocnik, U Stellenbosch, S Afr Med J 9/97 87:1116. This area is still very unclear with conflicting research findings. Studies of zinc in Alzheimer's are not clear and zinc could be a cause of Alzheimer's. A chelator of copper and zinc appears to improve Alzheimer's.

Zinc Confers Some Protection Against Lead Toxicity in Rat Study: Indian J Physiol Pharmacol. 1995 Oct;39(4):377-82; 

Low B-12 and Folate Doubles AD: Hui-Xin Wang of the Stockholm Gerontology Research Center tested 400 non-demented people aged 75 and over in the Kungsholmen Project with 3 years follow-up. Those with low levels of B-12 or folate, defined as less than 150 picomoles per litre of blood (pmol/l) and 10 nanomoles per litre (nmol/l) respectively, were twice as likely to have been diagnosed with AD three years later. Neurol 5/01