There’s an old joke that the world is divided into two types of people: those who dichotomise everything and those who don’t. But seriously, when it comes to attitudes on aging, the world really does seem to be divided into people who are determined to make it to at least 100 (including my mother, who at 93 is still living in her own home and intends to stay there until she’s carried out in a box), and those who are so averse to the whole idea of getting really elderly, that they’d literally rather die than reach advanced old age. For many people in that latter category, the major factor that puts them off wanting to live into their eighties, nineties and beyond, is the fear of cognitive decline and dementia. After all, who wants to live long enough to celebrate their one hundredth birthday if they’re too far gone to recognise any of the guests?
And yet, we’ve all encountered individuals who remain in remarkably good cognitive condition, all the way to the very end of their long lives. I had the great privilege of attending a public talk given by Eric Storm, dubbed ‘the man who lived in three centuries’, just a few months shy of his death, which sadly occurred only nine days before his 104th birthday. Unlike Joe Biden, Eric really was sharp as a tack. He spoke without notes, recounting events from decades ago as lucidly as he discussed current affairs. And he was still making money on the stock market (most of which he gifted to charity) almost right up to his death.1
How do people like Eric manage to stay sharp right up until the end of their long lives, when so many people lose their marbles at much younger ages? Without doubt, there are many factors that influence cognitive health at advanced age. But a large-scale dietary trial called DIRECT-PLUS has illuminated connections between food and brain health that should be grabbing the attention of anyone who wants to retain mental fitness into old age.
DIRECT-PLUS (a somewhat tortured acronym for Dietary Intervention RandomizEd Controlled Trial PoLyphenols Unprocessed Study) recruited participants from a rather unique setting: workers at the Nuclear Research Center Negev2, in Dimona, Israel. The Dimona research centre is an isolated workplace in the Negev Desert, which provides lunch to all employees and also has on-site medical facilities and a fitness centre.3 The researchers were specifically looking for metabolically unhealthy participants with abdominal adiposity (indicated by waist circumference over 102 cm for men, and over 88 cm for women) and/or dyslipidemia (elevated triglycerides and/or low HDL cholesterol). They found 294 such individuals, and randomly allocated them to one of three different interventions:
A physical activity (PA+HDG) group which received free gym memberships, a workout program and education sessions to encourage moderate-intensity physical activity (aerobic activity plus strength training), along with general guidelines on healthy eating;
A physical activity plus Mediterranean diet (PA+MED) group which received the same program as the PA+HDG group in addition to nutrition sessions which instructed participants to adopt a traditional Mediterranean diet “rich in vegetables and legumes and low in red meat, with poultry and fish replacing beef and lamb”. Participants were also supplied with a free daily allowance of 28 g walnuts.
A physical activity plus Mediterranean diet plus greens group (PA+green-MED) which received the same intervention as group 1, the 28 g of walnuts per day, and instructions to adopt a Mediterranean diet even lower in poultry, and red and processed meat, and higher in fish, than group 2. In addition, they were asked to drink three to four cups of green tea per day, and to incorporate 100 g of frozen cubes of Mankai (Wolffia globosa, also known as duckweed, a high-fibre and high-protein aquatic plant consumed in southeast Asia) into a green smoothie, to be used as partial replacement for animal protein at dinner. Both green tea and Mankai are particularly rich in plant compounds known as polyphenols (found in abundance in fruits, vegetables, wholegrains, legumes, nuts, herbs and spices), which have been suggested to play key roles in the health benefits associated with the Mediterranean diet.
All participants received lunches conforming to their dietary assignment, in their workplace cafeteria. Each group received a similar number of group sessions and level of personal guidance during the trial, in order to minimise one of the major sources of bias that often besets lifestyle intervention trials - namely, that the mere fact of being enrolled in a study, and receiving attention from research staff, tends to improve participants’ outcomes.
The researchers constructed these three interventions to test a hypothesis: if the well-established health benefits of the Mediterranean diet are at least partially attributable to its high polyphenol content and relatively low saturated fat content, would boosting the intake of polyphenols even higher, and restricting saturated fat intake even more, yield superior results in halting or even reversing the progression of cardiometabolic conditions that tend to worsen with age - including metabolic syndrome and dementia?
Many findings from this study have previously been published, including the following:
In participants with abdominal obesity and/or dyslipidaemia, after six months on their assigned program, the PA+MED and PA+green-MED groups lost a similar amount of weight, and both groups lost more than the PA + health dietary guidelines group (PA+green-MED -6.2 kg; PA+MED -5.4 kg, PA+HDG -1.5 kg). However, the PA+green-MED had a greater reduction in waist circumference (indicating more visceral fat loss), low-density lipoprotein cholesterol (LDL-C), diastolic blood pressure, homeostatic model assessment for insulin resistance (HOMA) - a marker of insulin sensitivity - and high-sensitivity C-reactive protein (hs-CRP), an inflammatory marker, than either of the other groups.
The PA+green-MED group lost 38.9 per cent of their intrahepatic fat (i.e. fat in their livers) - almost double the amount lost by the PA+MED group, which lost 19.6 per cent of their liver fat and more than three times as much as the PA+HDG group which lost 12.2 per cent.
Intrahepatic fat loss was independently associated with increased intake of Mankai and walnuts, decreased red/processed meat consumption, increased serum folate and adipokines/lipids biomarkers, and with changes in microbiome composition (beta-diversity) and several specific bacteria.The PA+green-MED group also had more than double the loss of visceral adipose tissue (VAT) compared to the PA+MED group, losing 14.1 per cent of their VAT vs 6 per cent in the PA+ MED group and 4.2 per cent in the PA+HDG group, independent of age, sex, waist circumference, or weight loss. In other words, the green-MED diet preferentially maximised reduction of the most dangerous type of fat - the deep belly fat that wraps around and intrudes into the abdominal and pelvic organs. The major determinants of VAT loss were higher dietary consumption of green tea, walnuts, and duckweed, lower red meat intake, and higher total plasma and urine polyphenols.
In a comparison of fasting levels of ghrelin (a hormone associated with hunger; low fasting levels are associated with obesity and metabolic syndrome), the PA+green-MED group had the greatest increase in ghrelin levels (10.5 per cent, compared to 1.3 per cent in the PA+HDG group and 5.4 per cent in the PA+MED group). Increases in fasting ghrelin level were associated with decreased insulin resistance and visceral fat, even after adjusting for relative weight loss.
The PA+green-MED group had the most significant change in gut microbiome composition at the end of the weight loss phase. Specific microbial taxa that increased in this group had previously been found to be in abundance in the gut microbiota of lean individuals. Greater adherence to the green-MED diet (i.e. more polyphenol-rich plants and less red and processed meat) was linked to both larger shifts in the gut microbiome and better cardiometabolic outcomes, including weight loss, blood pressure and insulin sensitivity.
Weight regain after weight loss is common. To explore the potential for autologous faecal microbial transplants (aFMT) in limiting weight regain, after six months of weight loss, faecal samples were taken from participants and processed for use as autologous faecal microbial transplants during the follow-up phase - that is, participants were randomised to receive either their own faecal samples, turned into ‘crapsules’, over the course of the next six months, or a placebo. The PA+green-MED group that received autologous faecal microbial transplants had significantly less weight regain than any of the other groups, and they also had superior results in terms of waist circumference, fasting insulin levels and insulin sensitivity.
In summary, the green-MED diet induced changes in the gut microbiome during the weight loss phase, which helped participants avoid regaining weight, and losing all the metabolic benefits associated with weight loss.
Given the well-established correlation between poor metabolic health and greater risk of cognitive decline, a logical step for the DIRECT-PLUS research team was to measure the impact of each intervention on brain aging. Our brains naturally atrophy (decrease in volume) as we get older, but those with the greatest loss of brain volume experience the most significant deterioration in cognitive function. Previous research found that people with a high degree of adherence to a Mediterranean diet pattern had reduced brain atrophy, such that their brain volumes were like those of people five years younger than them. Could the green-MED diet achieve even better results?
Participants in the DIRECT-PLUS trial underwent brain MRI scans at baseline, and after 18 months on their assigned intervention. Predictably, individuals over the age of 50 had more brain atrophy at the 18 month mark than younger participants. However, age-associated adverse changes in brain volume (namely, a decrease in hippocampal occupancy score [HOC], an index of the size of the hippocampus region of the brain which plays a vital role in memory and learning; and an increase in the lateral ventricle volume [LVV] expansion score, a proxy for brain tissue loss) were attenuated in participants assigned to either version of the Mediterranean diet, with the best outcomes in the green-MED group. When looking at the figures below, keep in mind that healthier brain aging means less reduction in HOC (or even an increase in HOC) and less increase in LVV:
Those whose insulin sensitivity had improved the most over the course of the study, whose blood pressure and LDL cholesterol had declined the most, and who had lost the most weight and waist circumference, had the least brain atrophy. Greater intake of Mankai, green tea, and walnuts and less red and processed meat consumption were all significantly and independently associated with reduced brain atrophy; in fact, people who consumed the most Mankai had a slight increase in HOC.
The latest publication by the DIRECT-PLUS team contains an analysis of the participants’ proteomes (i.e. the set of proteins expressed in their bodies), before and after the 18-month diet and exercise intervention. At baseline, they found that higher levels of two proteins, Galectin-9 (Gal-9) and Decorin (DCN), were associated with accelerated brain aging.
Gal-9 induces the release of proinflammatory cytokines, both throughout the body and in the brain, leading to increased production of cytokines such as interleukin-6 (IL-6) which is known to exacerbate neurodegeneration in Alzheimer’s disease. Higher levels of DCN in cerebrospinal fluid are associated with the early stages of amyloid-beta (Aβ) pathology, which plays a central role in the development of Alzheimer’s.
By the end of the trial, Gal-9 had significantly decreased among individuals whose brains had aged the least, while DCN significantly increased among those whose brains aged the most. Participants assigned to the green-MED diet significantly decreased Gal-9 compared to their own baseline measures, and compared to the healthy diet guidelines group. Changes in DCN levels failed to reach statistical significance:
Both drinking four cups of green tea per day, and eating seven portions of walnuts per week, were significantly associated with a reduction in Gal-9 levels.
The green road to better metabolic function and brain health
Let’s pull together all the published results from the DIRECT-PLUS trial: If you want better metabolic health - a smaller waistline, less liver and visceral fat, higher insulin sensitivity, lower LDL cholesterol and blood pressure - along with a gut microbiome that promotes leaner body composition, and you want to slow down brain aging so that you can make it to old age with all your marbles intact, you should be:
Drinking more green tea.
Eating walnuts every day.
Eating plenty of green vegetables. You’re unlikely to be able to buy Mankai at your local supermarket, but there are plenty of other leafy greens that you can incorporate into meals. Research on the Mediterranean-DASH Diet Intervention for Neurodegenerative Delay (MIND diet) score has established that a high intake of green leafy vegetables is effective at slowing down cognitive aging.
Eating less red and processed meats, and replacing them with legumes, nuts or fish.
Of course, it’s up to you whether you want to put the effort into making the diet and lifestyle changes that will help you preserve your physical and cognitive function into advanced old age. But if you could have five, or ten, or even fifteen or twenty additional trips around the sun, in great physical shape and fully compos mentis, so that you could spend more time with your loved ones and enjoy more of everything this wonderful planet has to offer, wouldn’t it be worth it? Personally, I think so.
For information on my private practice, please visit Empower Total Health. I am a Certified Lifestyle Medicine Practitioner, with an ND, GDCouns, BHSc(Hons) and Fellowship of the Australasian Society of Lifestyle Medicine.
Eric had made a great fortune as a stockbroker when he was far too young to spend his money wisely. Consequently, in his own words, he had eaten enough rich food to sink a battleship, and drunk enough booze to refloat it. A near-fatal heart attack at the age of 34 precipitated Eric’s Road to Damascus conversion to healthy living. He co-founded the Natural Health Society of NSW and was one of its major financial benefactors until his death.
Renamed the Shimon Peres Negev Nuclear Research Center in 2018, after the former Israeli prime minister, serial war criminal, and key figure in the development of Israel’s secret nuclear program - see Note 3.
It’s also the location of Israel’s undeclared nuclear weapons program. Israel is the only country in West Asia which possesses nuclear weapons, but it has not signed or ratified the Treaty on the Prohibition of Nuclear Weapons and has not accepted IAEA safeguards on its key facilities, including the Dimona plant. When Mordechai Vanunu blew the whistle on Israel’s nuclear weapons program in 1986, the Mossad (Israel’s national intelligence agency) used a honeypot scheme to lure him to Rome, then kidnapped him and illegally transported him back to Israel. He was convicted for espionage and leaking classified information, and sentenced to 18 years in prison, of which he served over 11 1/2 years in solitary confinement in a 3 x 2 metre cell. After his release, he was forbidden to leave Israel and is still banned from using the internet or mobile phones. I hope you appreciate the irony of a secretly nuclear-armed state that outrageously violates the rights of whistleblowers like Vanunu, supplying ‘cooked’ intelligence to launch an unprovoked attack on Iran’s nuclear facilities on the pretext that if that country developed nuclear weapons, it would be a threat to stability in the region. Pot, meet kettle.
Amazing amount of RESEARCH! THANK YOU SO MUCH FOR ALL !!
Loved this, so inspiring. Lucky indeed to have heard Eric and witness his ability. He paid back his bad habits in spades to us all.