Take Alzheimer’s, which accounts for two thirds of dementia, as an example. There are only three genes that can cause Alzheimer’s (APP, PSEN1, PSEN2), and these account for considerably less than one in a hundred cases of Alzheimer’s.
There are, however, 76 other genes which appear to confer a very small additional risk. Taken together, estimates suggest that 75-85% of the risk can be predicted by combining these into a ‘polygenic’ risk score. The single greatest predictor is the presence of the ApoE4 variant of the ApoE gene, carried by about one in five people. It contributes about 5% to one’s risk for Alzheimer’s disease.[4,5]
Predicting risk and actually reducing risk with changes to diet and lifestyle are two different things. The predictive risk for Alzheimer’s of having a low intake of seafood and/or omega-3 fats is 22%, and so is having a low intake of B vitamins resulting in a high blood Homocysteine is an amino acid found in the blood. Elevated levels of homocysteine have been associated with narrowing and hardening of the arteries, an increased… level. Smoking confers a similar risk. These are example of things you can do something about that actually make a difference.
I decided to take a look at really good studies where people had done something different – better diet, more B vitamins, more omega-3 intake. Good studies always check for those gene variations that increase risk. The two most common are ApoE4 and, in relation to B vitamins, a ‘methylation’ gene called MTHFR677TT which cranks up risk for lots of diseases from Alzheimer’s to schizophrenia and BRCA for breast cancer.
In every study I’ve looked at, once the bright light of an improved diet or nutrient intake shines, the dim light of genes fades into insignificance. A good example of this is a recent study in China, involving 29,072 people of which 20% had the ApoE4 gene. Each participant had their diet and lifestyle assessed over the 10 year period of the study to see who would or wouldn’t develop cognitive decline or dementia.
The study showed that whether or not a person had the ApoE4 ‘Alzheimer’s gene’ made no difference to the positive reduction in risk achievable by simple diet and lifestyle changes. “These results provide an optimistic outlook, as they suggest that although genetic risk is not modifiable, a combination of more healthy lifestyle factors is associated with a slower rate of memory decline, regardless of the genetic risk,” wrote the study authors. Those with a healthy vs unhealthy diet were nine times less likely to develop dementia.
Another example was a study of older people with mild cognitive impairment, about a third of participants had the MTHFR variant that increases Alzheimer’s risk. But supplementing with B vitamins almost arrested further memory decline and slowed the rate of brain shrinkage by 52%,[8,9] reducing shrinkage of the Alzheimer’s areas of the brain by 9-fold. Whether a person did or didn’t have this ‘Alzheimer’s’ gene made no difference at all to the beneficial effect of the B vitamins. The same has been shown in other studies giving omega-3 to reduce cognitive decline.
A gene variant is more like a dimmer switch and can be ‘over-expressed’ or ‘down-regulated’ – turned up or dimmed down. That is why approximately half of women with the BRCA gene develop breast cancer and half don’t. The environment the gene is exposed to makes all the difference. In this case soya dampens down the BRCA gene, hence reducing risk, while dairy increases risk. ‘Adherence to healthy dietary patterns (vegan) was significantly associated with the downregulation of pro-metastatic (cancer) genes.’ concludes a recent study in the European Journal of Nutrition on women with the BRCA gene. (11)
Too often genes are blamed as drivers of disease even though the primary drivers are what you put in your mouth or how you live your life – both factors under our control. For example, DNA genetic testing can cause panic when an individual is informed they have gene variants that increase their disease risk. Over-emphazing the importance of genes discourages people from preventing their own disease by improving diet and lifestyle.
Also, take a look at my report Most Dementia is Driven by Diet Not Genes.
- Bekris LM, Yu CE, Bird TD, Tsuang DW. (2010) Genetics of Alzheimer disease. J Geriatr Psychiatry Neurol. 23:213-227. https://pubmed.ncbi.nlm.nih.gov/210451632.
- Bellenguez C, Küçük F, Jansen IE, et al. (2022) New insights into the genetic etiology of Alzheimer-s disease and related dementias. Nat Genet. 54:412-436. https://pubmed.ncbi.nlm.nih.gov/353799923.
- Escott-Price V, Myers AJ, Huentelman M, Hardy J. (2017) Polygenic risk score analysis of pathologically confirmed Alzheimer disease. Ann Neurol. 82:311-314. https://pubmed.ncbi.nlm.nih.gov/28727176
- Heininger K (2000), A unifying hypothesis of Alzheimer’s disease. III. Risk factors. Hum Psychopharmacol Clin Exp. 15:1-70. https://pubmed.ncbi.nlm.nih.gov/12404343
- Ridge PG, Mukherjee S, Crane PK, Kauwe JSK, (2013) Alzheimer’s Disease: Analyzing the Missing Heritability. PLoS One. 8(11): e79771. https://pubmed.ncbi.nlm.nih.gov/24244562
- Beydoun MA, Beydoun HA, Gamaldo AA, et al. (2014) Epidemiologic studies of modifiable factors associated with cognition and dementia: systematic review and meta-analysis. BMC Public Health. 14:643. https://pubmed.ncbi.nlm.nih.gov/24962204
- Jia J, Zhao T, Liu Z et al. (2023) Association between healthy lifestyle and memory decline in older adults: 10 year, population based, prospective cohort study. BMJ 380:e072691. https://pubmed.ncbi.nlm.nih.gov/36696990
- Smith AD, Smith SM, de Jager CA, et al. (2010) Homocysteine-lowering by B vitamins slows the rate of accelerated brain atrophy in mild cognitive impairment: a randomized controlled trial. PLoS One. 5(9):e12244. https://pubmed.ncbi.nlm.nih.gov/20838622
- Smith AD, Refsum H. (2016) Homocysteine, B vitamins, and cognitive impairment. Annu Rev Nutr. 36: 211-239. https://pubmed.ncbi.nlm.nih.gov/27431367
- Douaud G, Refsum H, de Jager CA, et al. (2013) Preventing Alzheimer’s disease-related gray matter atrophy by B-vitamin treatment. Proc Natl Acad Sci USA 110:9523-9528. https://pubmed.ncbi.nlm.nih.gov/23690582
- Foroutan-Ghaznavi M, Mazloomi SM, Montazeri V, Pirouzpanah S. Dietary patterns in association with the expression of pro-metastatic genes in primary breast cancer. Eur J Nutr. 2022 Sep;61(6):3267-3284. doi: 10.1007/s00394-022-02884-1. Epub 2022 Apr 28. PMID: 35484415.
16. Jernerén F, Elshorbagy AK, Oulhaj A, et al. (2015) Brain atrophy in cognitively impaired elderly: the importance of long-chain Omega-3 fatty acids are considered essential fatty acids – they cannot be made within the body so must be obtained from the diet. EPA and… and B vitamin status in a randomized controlled trial. Am J Clin Nutr. 102:215-221. https://pubmed.ncbi.nlm.nih.gov/25877495
- Oulhaj A, Jernerén F, Refsum H, et al. (2016) Omega-3 fatty acid status enhances the prevention of cognitive decline by B vitamins in Mild Cognitive Impairment. J Alzheimer’s Dis. 50:547-557. https://pubmed.ncbi.nlm.nih.gov/26757190
- van Soest, A.P.M., van de Rest, O., Witkamp, R.F. et al. (2022) DHA is short for Docosahexaenoic Acid. It is an essential omega-3 fatty acid found in fish such as salmon, mackerel and herring, and is often… status influences effects of B-vitamin supplementation on cognitive ageing: a post-hoc analysis of the B-proof trial. Eur J Nutr. 61:3731-3739. https://pubmed.ncbi.nlm.nih.gov/35704085
- Jernerén F, Cederholm T, Refsum H, et al. (2019) Homocysteine Status Modifies the Treatment Effect of Omega-3 Fatty Acids on Cognition in a Randomized Clinical Trial in Mild to Moderate Alzheimer’s Disease: The OmegAD Study. J Alzheimers Dis. 69:189-197. https://pubmed.ncbi.nlm.nih.gov/30958356