Epidemiological studies and diet composition
The link between nutrition and health is supported by different kinds of studies:
Epidemiological studies provide so-called “ecological correlation” or a correlation between traditional food habits and health events at the population level. These “ecological correlation” studies describe a link between a geographical situation, a food tradition there, and the health of the population practicing that tradition.
For instance, the famous “seven countries study” in the sixties compared cardiovascular outcomes in comparable populations of 5 European countries, from Greece to Finland, plus Japan and the USA. Results emphasized the cardiovascular benefits of the “Mediterranean Diet” characterized by a high level of fruits, cheese, vegetables, fish, olive oil and wine.
Following these “ecological correlation” study results (a negative correlation between “all cause mortality” and vegetable consumption, or between fish and “cardiovascular mortality”, for instance), nutrition scientists raise hypotheses, try to demonstrate them with new trials, and describe more precisely the role of various nutrients.
The Mediterranean diet study, for instance, revealed the role of antioxidants and fibers from vegetables and the role of Omega 3 Fatty acids from fish and terrestrial sources like purslane and grass fed animals (rabbits, geese, sheep, goats, snails all typical of Mediterranean diet) in maintaining human health.
Today more than 50.000 scientific peer reviewed articles are dedicated to the link between immunity, inflammation and nutrition. A wealth of mechanistic and clinical data show that vitamins, including vitamins A, B6, B9, folate, B12, C, D, and E, trace elements, including zinc, iron, selenium, magnesium, and copper and the omega-3 fatty acids play important and complementary roles in supporting the immune system.
Epidemiological studies and “civilization diseases”
Modern epidemiology also describes a lot of “non-transmissible but epidemic” diseases such as obesity, diabetes, cancer, depression or neuro-degenerative and cardiovascular diseases. This group is called “civilization diseases”, or more precisely “low grade inflammatory diseases”.
“Food is our first Medicine” said Hippocrates, the Greek ancestor of all physicians, 2600 years ago. But food quality is not only based on the particular foods in our diet. It is also based on how that food is produced. That very much affects its nutritional composition.
Indeed, the quantity of immunity-affecting nutrients per amount of food product varies considerably according the way plants and animals are produced.
For instance, compliance with the main components of the Mediterranean diet (such as fruits & vegetables) is always positively associated with longevity, whereas the consumption of dairy products is negatively associated with longevity in some countries like Holland, but positively in Switzerland and some other mountain countries.
Epidemiologist call it “the Alpine paradox” and explain it with the fact that cheeses come from cows eating grass leaves (rich in Omega 3, see below) in mountain countries, and grain diets (rich in Omega 6) in lowlands areas with intensive crop production methods.
In the Mediterranean diet, vegetables and fruits are especially important because they provide the vitamins and antioxidants for approximately half of our dietary needs. But the variation in antioxidant content among those foods can vary from 1 to 100 for the same plant.
Antioxidants, omega 3s and other vitamins are nutrients necessary to our immunity. We need them, but their presence in basic food is linked to the way farmers produce the plants and animals from which we derive these nutrients.
The most impressive example is probably the impact of the Omega 6 – Omega 3 ratio in feed and food for our health.
Omega 3 and Omega 6: A documented and important example of the “Ecological correlation”
In the last half century, the physiological and biochemical effects of polyunsaturated fatty acids (PUFAs) Omega 6 and Omega 3 have been thoroughly investigated and are now better understood.
PUFAs are divided in two big families, Omega 6s and Omega 3s, that play antagonist roles in the inflammation process. And inflammation is the first step of the innate immunity process.Numerous biochemical explanations describe the biological pathways of inflammation. Inflammation is a biological defence response against physical, biological or infectious trauma to the body’s cells. It involves a whole series of processes whose purpose is:
– amplification or “promotion” phase,
– then to restore the affected tissues and homeostasis (equilibrium) in its reduction or “resolution” phase.
Omega 6s are involved in the pro-inflammatory process (promotion) while Omega 3s are involved in anti-inflammatory process (resolution). The recommended ratio between Omega 6s and Omega 3s on our plates for this purpose is 4. That is, four times as much Omega 6 as Omega 3.
Biochemistry means “Chemistry of Life” and sometimes the chemistry of life tells stories full of meaning. Omega 3 and Omega 6 precursors are only synthesized by plants, for example. Without plant synthesis, we would have no Omega 3s and no Omega 6s. But plants produce them primarily as short chain molecules, and animals have the enzymes to link them up and produce more long chain Omega 3s and long chain Omega 6s, which are very active and essential to our metabolism.
Omega 6s come mainly from grain or seeds, like corn or soybeans, while Omega 3s come primarily from leaves (together with B-9) such as grass, clover and alfalfa, as well as from algae and also from unusual and minor seeds like Flax or Chia.
So the Omega 6 and Omega 3 balance in the food chain is not only necessary to avoid inflammation dysfunction, is not only a biochemical ratio, but also a sum of good balances from the soil (crop rotation, diversity) to the animals’ diet and our plates (vegetal – animal balance).
Vegetable oils like corn oil, sunflower oil or soybean oil provide mostly Omega 6s. Palm oil provides mainly saturated fat, but also Omega 6. While olive oil and rapeseed (canola) oil provide mainly mono-unsaturated fatty acids.
The majority of the lipids consumed by humans in the western diet come from animals. If animals are fed with the universal corn-soy system, then milk, eggs, meats, cold cuts and even fish will become sources of (pro-inflammatory) Omega 6.
If animals are fed with grass, alfalfa and flax in soil, or on an algae based food chain in the ocean, then they will provide a lot of anti-inflammatory Omega 3.
This link between nutrition and health is key. The optimum recommended ratio is 4:1, or four Omega 6 for one Omega 3 in the diet.
Omega 6 / Omega 3 balance to resolve “low inflammatory civilization diseases”
– In Cardio Vascular (CV) diseases, Omega 6 favors platelet agregation, which is good for scarring but bad for fluid blood circulation, instead of Omega 3 action that favors blood fluidity, an important factor to prevent stroke and other vascular events.
– Omega 3s are the main component of brain and prevent neurologic troubles.
– Omega 6s favour cell development, including cancer cells, while Omega 3s limit them.
– Omega 6s favour inflammation, while Omega 3s limit them. (NB: Inflammation is a very important and positive function, but too much inflammation can be deleterious.)
– And Omega 6s help producing adipose cells to store energy as fat. (NB: This was an important function at the first stages of human evolution, but has become deleterious nowadays.)
Sources of Omega 6 (Corn/soy system) versus Omega 3 (rich plants)
Omega 3s (because of their particular multiple curvatures that play a role in the mobility of the cell’s membrane) are a massive component of the choroplasts in the plant leaves. Omega 6s are part of the energy storage of the seeds for germination.
So Omega 3s are abundant in spring, when leaves absorb solar enregy in the chloroplast. And Omege 6s are abundant at the end of summer, when plants put energy in the seed for the survival of the species. Only a very few plants (like flax and chia) have Omega 3s in their seeds.
From these facts, we can suggest:
– That Omega 3s present in all chroropyllic leaves are “spring and summer fatty acids”, the seasons of reproduction and birth while Omega 6s are “autumn fatty acids”, interesting to stimulate ingestion, store grain energy (lipogenesis) before winter times, and face various aggressions through the inflammation promotion process.
– The Meditarrenan area is an area of mountains and hills where leafy plants to feed men and animals are more abundant than grain. (See Mediterranean diet and its ecological positive correlation above)
Ailhaud & al. in 2006 showed that the breast milk balance for the Omega 6/Omega 3 ratio dropped from 5 to 22 between 1960 and 2000 due to changes in oil consumption in western countries, as well as changes in animal diets.
Hibbeln calculated the increase in soybean consumption and its consequences for Omega 6 (LA) in the USA in the 20th century. It is an impressive figure.
Figure 1: Soy consumption and LA (linoleic acid, main Omega 6 FA) consumption during the 20th century, USA
Disappearance is calculated from production data (here from various oleaginous seeds in the food chain) through both food and feed. Here we see that LA Omega 6 increased from 1.5% of the energy intake in the sixties, up to 8% of the total energy intake in 2000. LA is the precursor of all the Omega 6 family. This cannot be without consequences when we know the role of Omega 6 in inflammatory process.
Omega 6, Omega 3 and “Healthy eco-food barrier” during COVID-19 pandemic.
Covid-19 – The viral epidemic named Coronavirus-2019 disease (Covid-19) is responsible for symptomatic cases with fever, cough and sneezing. In most recent data, 10-15% of these symptomatic cases are complicated by severe pneumonia requiring hospitalization with a high risk of developing an Acute Respiratory Distress Syndrome (ARDS) that can lead the patient to the intensive care unit (ICU). Covid-19 general mortality rate is about 2% amongst symptomatic patients.
Up until now there has been no proven effective treatment/vaccine to heal/prevent the disease or to prevent its progression to a serious condition. The global burden of infection being high and worldwide, all kind of approaches deserve to be tested. Nutrition is of course one of the most promising approaches. It is interesting to emphasize that victims suffer from complications of inflammation. Specialists speak of an excessive “cytokine storm”. But, surprisingly, usual anti-inflammatory drugs are generally prohibited for the Covid-19 patients.
What happens when the coronavirus SARS-CoV-2 arrives ?
As soon as the virus enters the lung cell (pneumocyte), the mechanisms of innate immunity begin. Inflammation is the first step of the immune response. As seen above, the first phase of inflammation is called promotion phase and is driven by the Omega 6 Fatty-Acid (FA).
One of the Omega 6 FA family, called AA (Arachidonic Acid), stored in the cell membrane is then liberated (thanks to an enzyme named PLA2) and the inflammation process starts with oxygenase enzymes (like COX 1 and COX 2) which produce Omega 6 issued pro-inflammation mediators that lead to cytokine (protein of inflammation) production.
Omega 3 Fatty acids are also stored in the cell’s membrane (mainly EPA (EicosaPentaenoic Acid) and DHA (DocosaHexaenoic Acid), but, once they are liberated from the membrane (with the same PLA2 enzyme activity) they initiate, on the contrary (but through the same COX and LOX enzymes), an anti-inflammatory natural pathway.
In Figure 2 we see the two phases of inflammation. Dolor (Pain), Rubor (Redness) Calor (Heat) and Tumor (Swelling) were already described in the old Latin language by Roman Doctors twenty centuries ago. They are characteristic of the promotion phase. The body fight against aggressors, Promotion phase must happen very quickly: a question of seconds, minutes where Omega 6 stored in the attacked cell’s membrane are at the frontline as the first soldiers against aggression.
Then comes the resolution phase, after hours or sometimes days (when the battle is over and the aggressors killed), Omega 3s are active.
Too much promotion or not enough resolution and problems due to excess of inflammation appear. The tissues are repaired and they find their normal structure and role.
To have the good balance between promotion and resolution phases, the good ratio inside the membrane is supposed to be 4 Omega 6 for 1 Omega 3, or even less (3 to 1 ratio is sometimes recommended).
Anti-inflammatory drugs inactivate inflammation enzymes (PLA2, COX, LOX), so they inhibit pro-inflammatory processes (and leave the cell without defence against the virus) as well as anti-inflammatory pathways that stop or limit cytokine production.
So it is very important to have a good (low) Omega 6 / Omega 3 balance in each cell of our body. Omega 6 increased in the USA from 1.5% to 8% of total energy intake when Omega 3 remains stable or decreased. The changes in the fields (mainly due to the predominant corn-soy system) influence diet composition and unbalance the inflammation process. Harmony in the body is related with harmony and diversity in the fields.
From each piece of soil to each cell of our body
As mentioned above, Omega 6 and Omega 3 precursors are only synthesized by plants. If fields are full of Omega 6 rich plants like corn, sunflower, soybean, palm at the first step of the food chain, then our cells membrane will have a pro-inflammatory composition. On the contrary, if grass, alfalfa, clover, and other plants with leaves full of chloroplast (and some minor unusual seeds like flax), have their part, then the diversity in the soils will help to maintain a healthy membrane with less chemical input while our cells will have the good balance to regulate the pro- and anti- inflammatory pathways in our bodies.
Some pieces of the puzzle, (sometimes the link between science and health is like a police investigation, we need evidence from a lot of data)
ARDS (Acute Respiratory Distress Syndrome) and its lung oedema (build-up of fluid) are the worst consequences of the pro-inflammatory process that follows the viral Covid-19 infection.
A lot of human studies focused on the Omega 3 impact on ARDS. In these trials, fish oil rich in Omega 3s was used in enteral nutrition (passing through the intestine) as a treatment at high doses of Omega 3 (approximately 10 grams a day, which is 5 to 10 times more that the nutritional long term recommendation. In recent meta-analyses, it was found that this Omega 3 supplementation significantly reduced patients’ mortality by 36% as well as shortening duration of stay in the ICU and other data.
In animal studies, researchers used mice infested with bacteria and virus that were fed with standard diets or Omega 3 rich diets. The studies reported that dietary supplementation of Omega 3 PUFAs exert an overall beneficial effect. The survival rate increased significantly in the Omega 3 diet’s group and the microbial burden decreased. It was possible to measure in Omega 3-fed animals’ tissues a significant decrease of levels of pro-inflammatory cytokines.
Epidemiological data on Covid-19 are still to be discussed. Very preliminary observation comparing countries show that those with high fatty fish consumption have an optimal intake of omega-3 long chain PUFA of over 400 mg a day: Portugal (420), South Korea (450), Finland (470), Norway (500), Malaysia (700), Japan ( 760 ) and Iceland (900 ). These countries also have a very low number of victims related to the population: more than 4 times lower than the average of the other countries of the study (36 versus 175 deaths per million in June 2020).
Note that Omega 3 long chain PUFA consumption is estimated at 190 mg a day in the USA. Of course, no definitive conclusion can be drawn from this observation alone due to the large number of biases (linked to the varieties of social measures, the percentage of elderly people, the date of virus arrival, etc.) It is only a piece of the puzzle without any significance alone.
But… more than anything, in all western countries, the average consumption of Omega 3 is far below the recommendation of official guidelines when Omega 6 consumption is sufficient or excessive. Omega 3 consumption is often 3 to 4 times lower that the official recommendations. The breast milk Omega 6/Omega 3 ratio gives a value from 15 to 20 in western countries.
Co-morbidity factors for Covid-19 are always related to low-grade inflammatory diseases like obesity. Lack of Omega 3s is also linked to dysbiosis (imbalance) of gut microbiota. Gut microbiota influence health in protecting against pathogens and maintain gastrointestinal tract barrier integrity.
So, Human and Animal trials + consumption data + epidemiological data + Co-morbidity factors all together suggest that in case of an aggression such as a viral attack, the imbalance of our food chain fatty acids will be a very probable cause of an imbalance in our cells’ membrane composition that will cause an imbalance between pro- and anti- inflammatory pathways that can lead to cytokine storm, ARDS and even death.
May Omega 3 reduce COVID- 19 induced ARDS and save lives?
To move from hypothesis to evidence, we need dedicated human trials. Because there is a lot of scientific data to support this hypothesis about Omega 3s and COVID-19, trials are scheduled with the French research team to which I belong, including University biochemists and a University hospital physician for 2 trials: One with Covid-19 infected patients (secondary prevention) and another one with healthy but weak old people (primary prevention).
Conclusion and hopes…
For a new agriculture providing healthy foods with a good nutrient density: Back to “ecological correlation” and “Eco-Health”
We started with the so-called “ecological correlation” of the epidemiologists from last century. They found a relation between diet and health, then between diet, nutrients and health. It’s time now for a new paradigm, measuring the link between human health and the environment.
From diversity in the fields to balance in the cell’s membranes to prevent diseases because of an excess of inflammation, there is a connection that I discovered during my 45 year-long professional life. I started with concern about the soil’s health, promoting grass, lupine, horse beans, peas and flax. Then we measured that high Omega 3 (grass and flax) animal diets improve a cow’s fertility and reproductive data. Then we checked the impact of these Omega 3 diets on methane (a major ruminant Green House Gas) emission and we measured a large improvement. We measured also the nutritional value of animal products related to the quality of their feed, that led to my first clinical study, where we measured the impact of animal diets on human health.
Providing nutritious food that helps us through strengthening our immunity is a noble goal. Healthy food can protect us (as Hippocrates said). Microbial growth is absolutely dependent of their playing field, which is inside us.
This “One Health” or “Eco-Health” way is a narrow one, but it is also a beautiful one. Our human health is absolutely linked to animal health, planet health and soils health, mainly through a microbial link. Microbial life in the soils has an impact on animals and through them on food. It is not a marketing claim, it’s a patiently constructed scientific truth, and further research continues to make it stronger.
If you look at my publication list, you’ll find a lot of different topics about human health of course, but also animal health and the environment. We proved the impact of animal diet on human health. If farmers change from a corn-soy system to a grass fed + variety of seeds, we measured the impact on man’s insulin-resistance for instance, but also on a cow’s fertility, a soil’s organic matter, methane emission, etc.
For 25 years I was in the middle of a research movement with the other authors of those papers. Some had an interest in nutrition, others on the environment. It was not easy. If you say: “when animals are well fed, men will be healthier” everybody thinks it is evident. But the facts are sometimes difficult; the best is sometimes the enemy of the good. But when you find a measurable connection between a soil, an animal’s health and man’s health, it is fantastic. This is what I call “Eco-Health”.
Pierre Weill worked as a technical advisor for dairy farmers in Brittany, France. With some friends in 1992 he created and later became president of Valorex, a feed company that conducted trials linking animal feed with the nutritional quality of the resulting animal products. Their findings led to the founding in 2000 of the non-profit Bleu-Blanc-Coeur (BBC) to apply science to animal nutrition and sell high quality feed. Today BBC is active in 12 countries and represents 10% of French pigs, 7% of the country’s eggs and 5% of its milk.
We have omitted notes from this article for space reasons. Anyone wishing the original version of this article can get one by Emailing the editor for a copy. I will send it to you as a .docx attachment.
– Jack (TNF@nofa.org)