Alzheimers Disease

Several clinical trials have found that acetyl-L-carnitine supplementation delays the progression of Alzheimer’s disease,¹ improves memory,^2,3,4 and enhances overall performance in some people with Alzheimer’s disease.^5,6 However, in one double-blind trial, people who received acetyl-L-carnitine (1 gram three times per day) deteriorated at the same rate as those given a placebo.⁷ Overall, however, most short-term studies have shown clinical benefits, and most long-term studies (one year) have shown a reduction in the rate of deterioration.⁸ A typical supplemental amount is 1 gram taken three times per day.

An extract made from the leaves of the Ginkgo biloba tree is an approved treatment for early-stage Alzheimer’s disease in Europe. While not a cure, Ginkgo biloba extract may improve memory and quality of life and slow progression in the early stages of the disease. In addition, several double-blind trials have shown that ginkgo is helpful for people in early stages of Alzheimer’s disease, as well as for those experiencing another form of dementia known as multi-infarct dementia.^{9,10,11,12,13} Ginkgo has been found to be nearly as effective against Alzheimer's disease as donepezil, a prescription drug used to treat the condition.¹⁴ One trial reported no effect of ginkgo supplementation in the treatment of Alzheimer’s disease, vascular dementia or age-associated memory impairment.¹⁵ However, the results of this trial have been criticized, since analysis of the results does not separate those patients with Alzheimer’s disease or vascular dementia from those with age-associated memory impairment. A comparison of placebo-controlled trials of ginkgo for Alzheimer’s disease concluded that the herb compared favorably with two prescription drugs, donepezil and tacrine, commonly used to treat the condition.¹⁶ Research studies have used 120 to 240 mg of ginkgo, standardized to contain 6% terpene lactones and 24% flavone glycosides per day, generally divided into two or three portions. Ginkgo may need to be taken for six to eight weeks before desired actions are noticed. Ginkgo was not effective for preventing Alzheimer's disease in elderly volunteers with normal cognitive function or in those with mild cognitive impairment.¹⁷

Huperzine A is a substance found in huperzia (Huperzia serrata), a Chinese medicinal herb. In a placebo-controlled trial, 58% of people with Alzheimer’s disease had significant improvement in memory and mental and behavioral function after taking 200 mcg of huperzine A twice per day for eight weeks—a statistically significant improvement compared to the 36% who responded to placebo.¹⁸ Another double-blind trial using injected huperzine A confirmed a positive effect in people with dementia, including, but not limited to, Alzheimer’s disease.¹⁹ Yet another double-blind trial found that huperzine A, given at levels of 100 to 150 mcg two to three times per day for four to six weeks, was more effective at improving minor memory loss associated with age-related cognitive decline than the drug piracetam.²⁰ This study found that huperzine A was not effective in relieving symptoms of Alzheimer’s disease. Clearly, more research is needed before the usefulness of huperzine A for Alzheimer’s disease is confirmed.

In a double-blind trial, supplementation with an extract of lemon balm (Melissa officinalis) for 16 weeks significantly improved cognitive function and significantly reduced agitation, compared with a placebo, in people with Alzheimer's disease.²¹ The amount of lemon balm used was 60 drops per day of a 1:1 tincture, standardized to contain at least 500 mcg per ml of citral.

In a double-blind trial, supplementation with prolonged-release melatonin (2 mg each night for 24 weeks) significantly improved cognitive function and sleep quality, compared with a placebo, in patients with Alzheimer's disease.²² The beneficial effect of melatonin was more pronounced in patients who were suffering from insomnia than in those who were not, suggesting that poor sleep quality contributes to impaired cognitive function in people with Alzheimer's disease.

Lesser periwinkle contains the alkaloid vincamine. Supplementation with a semi-synthetic derivative of vincamine, known as vinpocentine, showed no benefit for people with Alzheimer’s disease in a preliminary study,²³ but vincamine itself was shown to be beneficial in a later double-blind trial.²⁴

In a double-blind study of people with Alzheimer’s disease, supplementing with sage for four months resulted in a significant improvement in cognitive function, compared with a placebo.²⁵ The amount of sage used was 60 drops per day of a 1:1 tincture. Although it is not known for sure how sage improves cognitive function, it appears to have an effect on acetylcholine, one of the chemical messengers (neurotransmitters) in the brain.

Vitamin B1 is involved in nerve transmission in parts of the brain (called cholinergic neurons) that deteriorate in Alzheimer’s disease.^26,27 The activity of vitamin B1-dependent enzymes has been found to be lower in the brains of people with Alzheimer’s disease.²⁸ It has therefore been suggested that vitamin B1 supplementation could slow the progression of Alzheimer’s disease. Two double-blind trials have reported small but significant improvements of mental function in people with Alzheimer’s disease who took 3 grams a day of vitamin B1, compared to those who took placebo.^29,30 However, another double-blind trial using the same amount for a year found no effect on mental function.³¹

In a preliminary study, people who used antioxidant supplements (vitamin C or vitamin E) had a lower risk of Alzheimer’s disease compared with people who did not take antioxidants.³² Other preliminary research shows that higher blood levels of vitamin E correlate with better brain functioning in middle-aged and older adults.³³ The possible protective effect of antioxidants may be explained by the observation that oxidative damage appears to play a role in the development of dementia.³⁴ Large amounts of supplemental vitamin E may slow the progression of Alzheimer’s disease. A double-blind trial found that 2,000 IU of vitamin E per day for two years extended the length of time people with moderate Alzheimer’s disease were able to continue caring for themselves (e.g., bathing, dressing, and other necessary daily functions), compared with people taking a placebo.³⁵ Another double-blind study found that 2,000 IU per day of vitamin E taken for an average of 2.3 years slowed the rate of decline in people with mild-to-moderate Alzheimer's disease.³⁶

Animal studies have found the Ayurvedic herb bacopa has constituents that enhance several aspects of mental function and learning ability.^38,39,40 A controlled study found that a syrup containing an extract of dried bacopa herb given to children improved several measures of mental performance.⁴¹ A double-blind trial in adults found that a standardized extract of bacopa (300 mg per day for people weighing under 200 lbs and 450 per day for people over 200 lbs) improved only one out of several measures of memory function after three months.⁴² Another double-blind trial lasting twelve weeks found 300 mg per day of bacopa improved four out of fifteen measures of learning, memory, and other mental functions in adults.⁴³ A third double-blind study found no effects on mental function in a group of healthy adults given 300 mg of standardized bacopa and tested two hours later. Bacopa has not been tested on people with memory problems.⁴⁴

In a preliminary report, two people with a hereditary form of Alzheimer’s disease received daily: coenzyme Q10 (60 mg), iron (150 mg of sodium ferrous citrate), and vitamin B6 (180 mg). Mental status improved in both patients, and one became almost normal after six months.⁴⁵

Most,^46,47,48,49 but not all,^50,51 studies have found that people with Alzheimer’s disease have lower blood DHEA (dehydroepiandrosterone) levels than do people without the condition. Emerging evidence suggests a possible benefit of DHEA supplementation in people with Alzheimer’s disease. In one double-blind trial, participants who took 50 mg twice daily for six months had significantly better mental performance at the three-month mark than those taking placebo. At six months, statistically significant differences between the two groups were not seen, but results still favored DHEA.⁵² In another clinical trial, massive amounts of DHEA (1,600 mg per day for four weeks) failed to improve mental function or mood in elderly people with or without Alzheimer’s disease.⁵³ It is likely that the amount of DHEA used in this trial was far in excess of an appropriate amount, illustrating that more is not always better.

DMAE (2-dimethylaminoethanol) may increase levels of the brain neurotransmitter acetylcholine. In one preliminary trial, people with senile dementia were given DMAE supplements of 600 mg three times per day for four weeks. The participants did not show any changes in memory, though some did show positive behavior changes.⁵⁴ However, a subsequent double-blind trial found no significant benefit from DMAE supplementation in people with Alzheimer’s disease.⁵⁵

In a double-blind trial, supplementing with the fatty acids present in fish oil (0.6 grams per day of EPA and 1.7 grams per day of DHA) for six months was not beneficial in people with Alzheimer's disease. However, in the subgroup of people with very mild cognitive impairment, supplementation with these fatty acids slowed the rate of cognitive decline compared with a placebo.⁵⁶

Some researchers have found an association between Alzheimer’s disease and deficiencies of vitamin B12 and folic acid;^57,58 however, other researchers consider such deficiencies to be of only minor importance.⁵⁹ In a study of elderly Canadians, those with low blood levels of folate were more likely to have dementia of all types, including Alzheimer’s disease, than those with higher levels of folate.⁶⁰ Little is known about whether supplementation with either vitamin would significantly help people with this disease. Nonetheless, it makes sense for people with Alzheimer’s disease to be medically tested for vitamin B12 and folate deficiencies and to be treated if they are deficient.

A double-blind trial of 20 to 25 grams per day of lecithin failed to produce improvements in mental function in people with Alzheimer’s disease.⁶¹ However, there were improvements in a subgroup of people who did not fully comply with the program, suggesting that lower amounts of lecithin may possibly be helpful. Lecithin supplementation has also been studied in combination with a cholinesterase inhibitor drug called tacrine, with predominantly negative results.^62,63,64,65

A small, preliminary trial showed that oral NADH (10 mg per day) improved mental function in people with Alzheimer’s disease.⁶⁶ Further studies are necessary to confirm these early results.

Phosphatidylserine (PS), which is related to lecithin, is a naturally occurring compound present in the brain. Although it is not a cure, 100 mg of PS taken three times per day has been shown to improve mental function, such as the ability to remember names and to recall the location of frequently misplaced objects, in people with Alzheimer’s disease.⁶⁷ However, subsequent studies have not validated these results. In one double-blind trial, only the most seriously impaired participants received benefits from taking PS; people with moderate Alzheimer’s disease did not experience significant improvements in cognitive function.⁶⁸ In another double-blind trial, people with Alzheimer’s disease who took 300 mg of PS per day for eight weeks had better improvement in overall well-being than those who took placebo, but there were no significant differences in mental function tests.⁶⁹ In another double-blind trial, 200 mg of PS taken twice daily produced short-term improvements in mental function (after six to eight weeks), but these effects faded toward the end of the six-month study period.⁷⁰

The PS used in these studies was obtained from bovine brain phospholipids. A plant source of PS is also available. However, the chemical structure of the plant form of PS differs from the bovine form. In a preliminary study, plant-derived PS was no more effective than a placebo at improving the memory of elderly people.⁷¹ Soy-derived PS was also ineffective in a double-blind study of elderly people with age-related cognitive decline.⁷²

Some researchers have found an association between Alzheimer’s disease and deficiencies of vitamin B12 and folic acid;^74,75 however, other researchers consider such deficiencies to be of only minor importance.⁷⁶ In a study of elderly Canadians, those with low blood levels of folate were more likely to have dementia of all types, including Alzheimer’s disease, than those with higher levels of folate.⁷⁷ Little is known about whether supplementation with either vitamin would significantly help people with this disease. Nonetheless, it makes sense for people with Alzheimer’s disease to be medically tested for vitamin B12 and folate deficiencies and to be treated if they are deficient.