Chapter 128
Is There a Threshold Effect?
No one other than Dr. Casimir Funk coined the term “vitamins.” In 1912, in a groundbreaking paper, he discussed the idea that complex compounds exist that our body cannot make itself, so we must obtain them through food. By the middle of the 20th century, all the vitamins had been discovered and isolated, but it wasn’t until the 1960s that it was recognized that certain fats are also crucial, including omega-3 fatty acids, which are concentrated in foods such as flaxseed and walnuts. Our body can convert these into the long-chain omega-3 fatty acids DHA and EPA, which we also find preformed in algae or fish.
The fact that it took so long, under sometimes extreme circumstances, to demonstrate the importance of omega-3 fatty acids (see.nf/essentialfats) shows how hard it is to develop an obvious omega-3 deficiency. Of course, the amount needed to prevent a deficiency is not necessarily what is best for health, as we see with scurvy. For the general population, there appears to be no cognitive benefit of long-chain omega-3 supplementation, but might it help those who don’t eat fish?
Consider the famous study Multidomain Alzheimer Preventive Trial, in which more than 1000 older adults with memory problems were randomized for three years to receive DHA and EPA (in fish oil) or a placebo. Overall, DHA and EPA had no significant effect on the rate of cognitive decline. However, most participants ate fish and thus were already consuming preformed DHA and EPA in their diets. Perhaps there is a threshold for protection, and they were all already above it from the start. The fact that no benefit was found in such studies of the general population does not yet mean a final verdict on the role of long-chain omega-3 fatty acids in brain health. That would be like giving half of these people oranges, finding no difference in scurvy rates (zero in both groups), and concluding that vitamin C plays no role in scurvy.
Couldn’t one go back to the data from the study above and examine only what happens among those who eat little fish (inferred retrospectively from their low blood levels of long-chain omega-3 fatty acids)? That’s exactly what the researchers did, and they found that, at least on one measure of executive function, deterioration in the fish oil group was significantly less than in the placebo group.
With post-hoc analyses, however, one must always be cautious, so the results should be viewed as exploratory rather than probative. Still, this could explain why clinical trials of long-chain omega-3 fatty acids so often fail. Perhaps it’s because they don’t focus on the people who stand to benefit the most—namely, those who start out with low levels.
Omega-3 Supplements
So should people who don’t eat fish take DHA and EPA for optimal brain health? I explore this question in see.nf/dhabrain. I’ll jump straight to the study results: A randomized, placebo-controlled double-blind trial in cognitively intact older adults found that after about six months of supplementation with long-chain omega-3 fatty acids, there was both a significant improvement in executive function and significantly less brain shrinkage than with placebo. In cognitively impaired older adults, a similar twelve-month study with algae-based DHA showed a significant improvement in cognitive function (including overall IQ) and in hippocampal volume—that’s where memory resides—but not in the placebo group. Adequate intake of the long-chain omega-3 fatty acids EPA and DHA could therefore be important for maintaining brain function and structure. But what does “adequate” mean, and how do we get there?
As I describe in the video, people who don’t eat fish tend to fall below a tentatively assumed omega-3 threshold that can be reached by taking 250 milligrams of a mixture of contaminant-free EPA and DHA from algae. Technically speaking, ALA is the only truly essential omega-3, the plant-based, short-chain omega-3, because we can make DHA and EPA from it. However, the efficiency of this conversion varies and may decline with age. So while most DHA supplementation studies have not been able to halt cognitive decline in the general population, non-fish-eaters, until we know more, should consider a supplement of 100 to 300 milligrams of DHA daily.
Why Not Just Eat Fish?
The comprehensive investigation by the World Health Organization, which could not find any notable cognitive benefits from supplementation with long-chain omega-3 fatty acids, suggests that any potential benefit may be offset by the potential neurotoxic contamination of fish and fish oil products with heavy metals, organochlorines, polychlorinated biphenyls, and polycyclic aromatic hydrocarbons. This could be an explanation for studies in which higher fish intake was associated with worse cognitive function. Most such findings come from studies of children, but higher omega-3 levels are also associated with a greater degree of cognitive impairment and dementia in older adults.
Details on the current studies can be found at see.nf/fishbrain. Here is just one illuminating case report: A 91-year-old man with years of progressive memory loss was diagnosed with Alzheimer’s. Cognitive tests showed that he had dementia, and his friends and family assumed he was nearing the end of his life. A history revealed that he had eaten swordfish once or twice a week for several years, and he had markedly elevated mercury levels. However, when he avoided mercury-containing fish for ten months, his levels fell to normal, his memory recovered, and cognitive tests showed that he was no longer demented. So it appears he may not have had Alzheimer’s at all, but rather mercury poisoning from a few servings of contaminated fish per month.
A systematic review and meta-analysis of toxic metals and Alzheimer’s found that blood levels of mercury and another heavy metal, cadmium, were significantly higher in Alzheimer’s patients than in control subjects. Switching to a plant-based diet can cut cadmium (and lead) levels in half within just three months and reduce hair-sample mercury levels by 20 percent. But once you return to a normal omnivorous diet, heavy metal levels shoot back up. Whether that can explain data showing dementia rates two to three times lower among vegetarians is unclear. Blood mercury levels are related to Alzheimer’s risk, but brain mercury levels determined at autopsy do not correlate with brain pathology.
Maybe mercury is just a marker of fish consumption, and the real culprit is one of the other contaminants such as PCB, which can lodge in our bodies for decades. If so, what about purified fish oil? The methods used in manufacturing, such as distillation, leave substantial amounts of PCB and other contaminants in the product. So if you take salmon, herring, and tuna oil as recommended, you far exceed the allowable daily toxin dose. Fortunately, you can get the benefit without the harm by instead deriving DHA from algae, which is what fish rely on as well. So we can skip the fish in the middle and obtain DHA directly from the source at the bottom of the food chain.
BMAA in Seafood
The famous neurologist Oliver Sachs and his colleagues unraveled the nested puzzle of a mysterious disease that clustered on an exotic tropical island and seemed to consist of three neurodegenerative diseases at once: the Parkinson-ALS-dementia complex. The affected natives ate fruit bats, which ate the seeds of a tree fruit in which a neurotoxin called BMAA had accumulated from a blue-green alga that grows in the tree roots. As I document in see.nf/alsfish, BMAA drew worldwide attention when it was found in the brains of Florida residents who had died of Alzheimer’s, and in Florida seafood in similar amounts to those in the contaminated fruit bats.