Food Synergy Principle

Holistic Food synergy is one of the most important biological mechanism to restore general homeostasis and reach a long healthy lifespan.  In this page, I’ll first explain what food synergy is (Section A), then ill show its health effects (Section B) and conclude on the need to redefine nutrition science (Section C)

Section A

Food Synergy and Culinary Combination

Holistic Food Synergy involves multiple parameters, from non refined whole food, to food combination, to proper feeding of the microbiota, to timing, spacing of meals, caloric intake, nutrient-strong superfoods, purety of foods (free from chemicals, molds & harmful bacteria), food environment, origin of food (garden versus far away), genetic expression and more. The following analysis sums up its important in both health and longevity.

“ Reduced food intake, avoiding malnutrition, can ameliorate aging and aging-associated diseases in invertebrate model organisms, rodents, primates, and humans. Recent findings indicate that meal timing is crucial, with both intermittent fasting and adjusted diurnal rhythm of feeding improving health and function, in the absence of changes in overall intake. Lowered intake of particular nutrients rather than of overall calories is also key, with protein and specific amino acids playing prominent roles. Nutritional modulation of the microbiome can also be important, and there are long-term, including inter-generational, effects of diet. The metabolic, molecular, and cellular mechanisms that mediate both improvement in health during aging to diet and genetic variation in the response to diet are being identified. These new findings are opening the way to specific dietary and pharmacological interventions to recapture the full potential benefits of dietary restriction, which humans can find difficult to maintain voluntarily. (Source)

In this above-mentioned context, food combination is one of the most important aspects of nutrition. In effect, research has shown that the health benefits of certain food is greatly enhanced when coupled with a complementary food. This concept is defined as “food combition” and more recently as “food synergy”.  In this perspective, nutritional scientists have summed up one working definition of food synergy.

 “The concept of food synergy is based on the proposition that the interrelations between constituents in foods are significant. This significance is dependent on the balance between constituents within the food, how well the constituents survive digestion, and the extent to which they appear biologically active at the cellular level. Many examples are provided of superior effects of whole foods over their isolated constituents. The food synergy concept supports the idea of dietary variety and of selecting nutrient-rich foods”. (1) (Source)

In this light, we have reviewed the scientific literature to support the argument that holistic synergy-based foods rather than mono-diets, the American food pyramid,  dietary supplements etc, should be the priority if one desires optimization of health and longevity.

Section B

Benefits and Harm in different Food Combination

Superfood Synergy Benefits


Superfood element of Food Synergy

Superfoods are foods that stand out from the rest because of their unusually dense nutrient content. Superfoods generally have high amounts of antioxidants, vitamins, and minerals, for instance, and many also contain healthy fats, high-quality protein, and fiber. What superfoods don’t contain are added sugars, synthetic fats, and food additives, such as artificial colors and flavors.

Most any food that is heavily processed will not stand up to superfood criteria – but once you’re eating primarily whole foods—foods that are as close to their natural state as possible—then basically everything you eat is a “superfood.”

You need nutrients—all of them—and nutrients are found in abundance in fresh whole foods. That being said, certain superfoods can be combined with great synergy, which means that the whole is greater than the sum of its parts.

The following superfood combinations in particular, which were compiled by TIME,1 may be even healthier than eating the same foods on their own.

Superfood Combinations

1. Tomatoes + Olive Oil

Lycopene — a carotenoid antioxidant that gives fruits and vegetables like tomatoes and watermelon a pink or red color — is one of the key reasons why tomatoes are so good for you.

However, when you eat tomatoes with olive oil, the antioxidant activity of the lycopene is increased.2 Lycopene is a fat-soluble nutrient, which means eating it with some dietary fat is essential in order for it to be properly absorbed. But this doesn’t explain the whole picture.

When researchers combined tomatoes with sunflower oil, the activity of lycopene did not increase, which suggests there’s something especially beneficial about the olive oil.

If you’re a fan of tomato sauce, you’re in luck as well, as lycopene is one example of a nutrient that becomes more bioavailable when it’s cooked. Research shows that cooking tomatoes (such as in tomato sauce or tomato paste) increases the lycopene content that can be absorbed by your body.

It also increases the total antioxidant activity. So one of the healthiest ways to consume tomatoes may be in an organic tomato sauce, drizzled with organic olive oil.

2. Wild-Caught Salmon + Collard Greens

Vitamin D helps your body to absorb calcium. In fact, if you have a vitamin D deficiency, it can cause a defect in putting calcium into the collagen matrix in your skeleton, leading to aches and pains.

In addition to being rich in vitamin K and phytonutrients that may help lower oxidative stress, fight inflammation, and prevent cancer, collard greens are rich in calcium. Wild-caught Alaskan salmon, meanwhile, contains some vitamin D, so consuming them together could theoretically be beneficial.

Wild-caught Alaskan salmon is high in healthy omega-3 fats and low in hazardous contaminants, and has about 988 IUs of vitamin D per 3.5-ounce serving.

It’s important to note that farm-raised salmon does not have nearly this level of vitamin D, with only 245 IUs per 3.5-ounce serving.3

It is difficult, however, to get optimal levels of vitamin D from your diet alone, and a better solution is to get sensible exposure to the sun or a high-quality tanning bed.

This will ensure you have adequate vitamin D levels to absorb the dietary calcium you consume.

If you decide to take a vitamin D supplement, keep in mind that it will increase your body’s need for vitamin K2. So when supplementing with oral vitamin D3, you need to make sure you’re also increasing your K2 and magnesium intake.

The biological role of vitamin K2 is to help move calcium into the proper areas in your body, such as your bones and teeth. It also helps remove calcium from areas where it shouldn’t be, such as in your arteries and soft tissues.

So vitamin K2 deficiency is actually what produces the symptoms of vitamin D toxicity, which includes inappropriate calcification that can lead to hardening of your arteries. If you want a natural dietary source of vitamin K2, fermented vegetables made with Kinetic Culture will produce high levels of K2.

3. Broccoli + Tomatoes

In addition to lycopene, tomatoes are an excellent source of lutein, zeaxanthin, and vitamin C (which is most concentrated in the jelly-like substance that surrounds the seeds), as well as vitamins A, E, and the B vitamins, potassium, manganese, and phosphorus.

Broccoli, meanwhile, is rich in vitamin K, vitamin C, folate, fiber and cancer-fighting compounds like sulforaphane. When rats were fed diets containing 10 percent broccoli, they had a 42 percent decrease in the growth of prostate cancer tumors.

When they were fed a diet containing 10 percent tomatoes, the growth rate dropped by 34 percent.

But when the rats were fed a diet with 10 percent broccoli and 10 percent tomatoes combined, the tumor weights decreased by 52 percent.4 So add some steamed broccoli to your tomato sauce or some raw broccoli and chopped tomatoes to your salad to boost their health potential.

4. Green Tea + Black Pepper

Black pepper contains a substance called piperine, which not only gives it its pungent flavor, but also blocks the formation of new fat cells.5 When combined with capsaicin and other substances, black pepper was also found to burn as many calories as taking a 20-minute walk.6

As an aside, black pepper also increases the bioavailability of just about all other foods — herbs and other compounds included. Green tea, for instance, is recognized as an abundant source of epigallocatechin-3-gallate (EGCG), a catechin polyphenol shown to boost metabolism and protect against cancer.

Research shows that when EGCG is administered in combination with piperine, it increases the absorption of EGCG and helped it stay in the bloodstream longer. If the idea of sprinkling black pepper in your tea isn’t appealing, TIME suggests:7

“Use the pair to soak meat or seafood. ‘Brewed tea with garlic, ginger, and black pepper makes a perfect marinade,’ [Cynthia] Sass [RD, MPH] says.”

5. Turmeric + Black Pepper

Turmeric, the yellow-pigmented “curry spice” often used in Indian cuisine, contains curcumin, the polyphenol identified as its primary active component and which exhibits over 150 potentially therapeutic activities, which include antioxidant, anti-inflammatory, and anti-cancer properties.8

Black pepper or piperine is sometimes added to turmeric because it’s believed to “heat up” the digestive system, which may help increase absorption. According to Melissa Rifkin, RD, a bariatric dietitian at Montefiore Medical Center in New York City, “If you pair the turmeric with the piperine, it improves the bioavailability of curcumin by 1000 times.” 9

6. Brussels Sprouts + Olive Oil

Brussels sprouts contain sulfur-containing compounds called glucosinolates, which your body uses to make isothiocyanates. These activate cancer-fighting enzyme systems in your body. Brussels sprouts have been linked to the prevention of a number of cancers, including colon cancer,10 ovarian cancer,11 and others.

Brussels sprouts are also rich in vitamin K, with about 243 percent of the recommended daily value in one cup. Vitamin K is a fat-soluble nutrient, so eating Brussels sprouts along with a healthy fat like olive oil will help increase its absorption. Rich in monounsaturated fats, olive oil may help lower your risk of heart disease and may even benefit insulin levels and blood sugar control, helping to lower your risk of type 2 diabetes.

7. Kale + Almonds

Just one cup of kale will flood your body with disease-fighting vitamins K, E, A, and C, along with respectable amounts of manganese, copper, B vitamins, fiber, calcium, and potassium. With each serving of kale, you’ll also find more than 45 unique flavonoids, which have both antioxidant and anti-inflammatory benefits.12

Vitamins K, E and A are fat-soluble, which is where the almonds come in to help ensure proper absorption. Almonds contain healthy monounsaturated fat, although one of the healthiest aspects of almonds appears to be their skins, as they are rich in antioxidants including phenols, flavonoids, and phenolic acids, which are typically associated with vegetables and fruits.

A study in the Journal of Agricultural and Food Chemistry even revealed that a one-ounce serving of almonds has a similar amount of total polyphenols as a cup of steamed broccoli or green tea.13 Almonds pair well with kale, for example slivered almonds atop a kale salad. However, any nut will do. My personal favorites are macadamia nuts and pecans.

8. Dark Chocolate + Apples

Eating apples is associated with a lower risk of death from heart disease, an association that’s thought to be related to their content of antioxidant flavonoids,14 including the anti-inflammatory quercetin. Dark chocolate, which is rich in antioxidant catechins, has also been found to support heart health. In one study, the highest levels of chocolate consumption were associated with a 37 percent reduction in cardiovascular disease and a 29 percent reduction in stroke compared with the lowest levels.15 According to Rifkin:

“When paired, they [dark chocolate and apples] have been shown to help break up blood clots.”

A couple of caveats… because much of the antioxidant content of an apple is found in its peel, you’ll want to leave the peel on when you eat it. For this reason, look for organic apples, which will be free from pesticides and other chemicals. For chocolate, the closer your cocoa is to its natural raw state, the higher its nutritional value. Ideally, your chocolate or cocoa should be consumed raw (cacao). When selecting chocolate, you can optimize its nutritional punch by looking for higher cacao and lower sugar content.

In general, the darker the chocolate, the higher the cacao. However, cacao is fairly bitter, so the higher the percentage cacao, the more bitter it is (the flavanols are what make the chocolate bitter, so manufacturers often remove them. But, it’s those flavanols that are responsible for many of chocolate’s health benefits). To counteract the bitterness, most chocolate is sweetened, so it’s a matter of balancing nutritional benefit with palatability.

9. Garlic + Wild-Caught Alaskan Salmon

A study published in the American Journal of Nutrition found that in men with high cholesterol, those who consumed 900 milligrams of garlic and 12 grams of fish oil decreased LDL cholesterol by 9.5 percent.16 It’s thought that eating wild-caught salmon with garlic may offer similar benefits, although you probably won’t be eating it every day, which is where an animal-based omega-3 fat supplement like krill oil can be beneficial.

Still, garlic is rich in manganese, calcium, phosphorus, selenium, and vitamins B6 and C, so it’s beneficial for your bones as well as your thyroid. It’s thought that much of garlic’s therapeutic effect comes from its sulfur-containing compounds, such as allicin, which are also what give it its characteristic smell. Garlic also has antibacterial, antiviral, and anti-fungal properties, making it one food that’s beneficial to consume as often as you like.

10. Black Beans + Red Bell Pepper

Black beans are a good source of non-heme iron (the kind found in plants), which is more difficult for your body to absorb. Combining black beans with a vitamin-C-rich food, like red bell pepper, may increase the absorption of non-heme iron by six times. Some people, particularly men and post-menopausal women, may have problems with elevated iron levels. I recommend checking your iron levels regularly using a simple blood test called a serum ferritin test; your ferritin level should be between 20 and 80 ng/ml, and 40 to 60 is ideal. If your iron levels are elevated, donating blood is one of the best solutions.

There are other reasons to eat black beans and peppers outside of the iron, of course. Black beans are a good source of folate, dietary fiber, manganese, protein, magnesium, vitamin B1 (thiamin), phosphorus, and antioxidants. Bell peppers, aside from being rich in vitamin C, also contain vitamin K, thiamin, niacin, folate, magnesium, and copper, along with phenolic compounds and antioxidant carotenoids.

Red Wine + Almonds =

react-text: 583 Has anyone ever told you that red wine is good for you? Well it’s nothing but true. Red wine contains an active antioxidant called /react-text resveratrol react-text: 586 , which improves heart health and blood vessel lining. Resveratrol becomes increasingly beneficial to the body when consumed with vitamin E (almonds). The American Journal of Enology and Viticulture compared several types of wine from around the world and found that /react-text pinot noir wines had the highest resveratrol levels react-text: 589 . You might want to keep this in mind next time you reach for a glass of wine! /react-text


Mol Nutr Food Res. 2011 Aug;55(8):1169-76. doi: 10.1002/mnfr.201100117. Epub 2011 Jun 29.

Enhancing the bioavailability of resveratrol by combining it with piperine.

Johnson JJ1, Nihal M, Siddiqui IA, Scarlett CO, Bailey HH, Mukhtar H, Ahmad N.

Author information



Resveratrol (3,5,4′-trihydroxystilbene) is a phytoalexin shown to possess a multitude of health-promoting properties in pre-clinical studies. However, the poor in vivo bioavailability of resveratrol due to its rapid metabolism is being considered as a major obstacle in translating its effects in humans. In this study, we examined the hypothesis that piperine will enhance the pharmacokinetic parameters of resveratrol via inhibiting its glucuronidation, thereby slowing its elimination.


Employing a standardized LC/MS assay, we determined the effect of piperine co-administration with resveratrol on serum levels resveratrol and resveratrol-3-O-β-D-glucuronide in C57BL mice. Mice were administered resveratrol (100 mg/kg; oral gavage) or resveratrol (100 mg/kg; oral gavage)+piperine (10 mg/kg; oral gavage), and the serum levels of resveratrol and resveratrol-3-O-β-D-glucuronide were analyzed at different times. We found that the degree of exposure (i.e. AUC) to resveratrol was enhanced to 229% and the maximum serum concentration (C(max)) was increased to 1544% with the addition of piperine.


Our study demonstrated that piperine significantly improves the in vivo bioavailability of resveratrol. However, further detailed research is needed to study the mechanism of improved bioavailability of resveratrol via its combination with piperine as well as its effect on resveratrol metabolism.

Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KG

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Br J Nutr. 2014 Jul 28;112(2):203-13. doi: 10.1017/S0007114514000737. Epub 2014 May 7.

Effects of resveratrol alone or in combination with piperine on cerebral blood flow parameters and cognitive performance in human subjects: a randomised, double-blind, placebo-controlled, cross-over investigation.

Wightman EL1, Reay JL2, Haskell CF1, Williamson G3, Dew TP3, Kennedy DO1.

Author information


Previous research has shown that resveratrol can increase cerebral blood flow (CBF) in the absence of improved cognitive performance in healthy, young human subjects during the performance of cognitively demanding tasks. This lack of cognitive effects may be due to low bioavailability and, in turn, reduced bioefficacy of resveratrol in vivo. Piperine can alter polyphenol pharmacokinetics, but previous studies have not investigated whether this affects the efficacy of the target compound. Therefore, the objective of the present study was to ascertain whether co-supplementation of piperine with resveratrol affects the bioavailability and efficacy of resveratrol with regard to cognition and CBF. The present study utilised a randomised, double-blind, placebo-controlled, within-subjects design, where twenty-three adults were given placebo, trans-resveratrol (250 mg) and trans-resveratrol with 20 mg piperine on separate days at least a week apart. After a 40 min rest/absorption period, the participants performed a selection of cognitive tasks and CBF was assessed throughout the period, in the frontal cortex, using near-IR spectroscopy. The presence of resveratrol and its conjugates in the plasma was confirmed by liquid chromat

ography-MS analysis carried out following the administration of the same doses in a separate cohort (n 6). The results indicated that when co-supplemented, piperine and resveratrol significantly augmented CBF during task performance in comparison with placebo and resveratrol alone. Cognitive function, mood and blood pressure were not affected. The plasma concentrations of resveratrol and its metabolites were not significantly different between the treatments, which indicates that co-supplementation of piperine with resveratrol enhances the bioefficacy of resveratrol with regard to CBF effects, but not cognitive performance, and does this without altering bioavailability.


PMID: 24804871 DOI: 10.1017/S000711451400073


5 ounce wine glass 500 mcg resvera vs 20 mg pill min  and most 100 mg for dosage…




Reference and Precision Notes


1, 7, 9 TIME March 12, 2015

Free Radical Biology and Medicine Volume 29, Issue 10, 15 November 2000, Pages 1051–1055

Vital Choice February 26, 2007

Cancer Res January 15, 2007 67; 836

Biochem Pharmacol. 2012 Dec 1;84(11):1501-10.

University of Oklahoma, Public Affairs

GreenMedInfo, Curcumin Health Benefits: 160 Pharmacological Actions

10 arcinogenesis. 2003 Mar;24(3):491-5.

11 Mol Cancer. 2010 Mar 2;9:47.

12 Journal of Agricultural and Food Chemistry. 57(16):7401-7408.

13  J. Agric. Food Chem., 2006, 54 (14), pp 5027–5033

14 Lancet. 1993 Oct 23;342(8878):1007-11.

15 BMJ. 2011 Aug 26;343:d4488.

16 Am J Clin Nutr February 1997 vol. 65 no. 2 445-450

Cell. 2015 Mar 26;161(1):106-18. doi: 10.1016/j.cell.2015.02.020.   food synergy

EXTRA  to be inserted

General principles regarding Food Combination



Acid and Alkaline Enzymes

Let’s take a look at a protein and starch, like a beef burger with a bun.

Protein requires an acidic environment to digest and the digestive enzyme pepsin, while carbohydrates require an alkaline environment and the digestive enzyme, ptyalin (1).

Since beef and bread have opposite digestive requirements, eating them together at the same meal causes the body to release both acid and alkaline solutions.

Acid and alkaline solutions neutralize each other, which can slow down digestion and cause bloating or fatigue.

Improper food combinations can also “confuse” the body, by demanding the body to release several types of digestive enzymes at once. This can further slow down digestion, and cause the infamous post-meal sluggishness by using up even more of the body’s digestive energy.

Understanding food combining rules can also help support the health of your entire gut. When digestive function is slow, food has the opportunity to putrefy and ferment in your digestive tract, which can cause the release of toxins (2).

When food is poorly digested, undigested food particles can also end up in your bloodstream and cause food sensitivities.

Undigested food can also feed the “unfriendly” bacteria in your gut, such as yeast, which can result in digestive conditions like candida.

On the other hand, there are certain foods that combine well together, based on their digest requirements, which we’ll get into in just a moment.

So, what do you think— is food combining just a myth?

Let’s go into more detail about how food combining works, so you can decide for yourself.

How to Start Food Combining For Improved Digestion

These basic food combining rules go hand-in-hand with eating for energy, and are designed to help you steer clear of the discomfort you can feel from poor digestion.

1. Eat Fruit Alone

While there’s nothing better than having a fruity dessert after your meal, combining fruit with other foods is a recipe for digestive disaster. This is because fruit is a simple sugar that digests very rapidly, in roughly 20 to 30 minutes.

Since fruit digests faster than any other food, it’s best eaten alone.

Let’s say, for example, you decided to have a fruit salad with your eggs. Eggs are a protein, which can take between 3 to 4 hours to digest. Since the fruit only takes 20 to 30 minutes to digest, combining it with a protein will create a gastrointestinal (GI) tract traffic jam.

That’s why it’s also best to avoid eating fruit right after meals.

Most people aren’t bothered when they combine fruit with leafy greens or celery since they are mostly water.

But as a general rule, fruit is best eaten alone on an empty stomach so that it doesn’t have the chance to ferment.

Fermentation in your GI tract not only leaves you feeling gassy and bloated, but can also create a feast for unfriendly bacteria.

It’s still important to eat fruit even though it doesn’t combine well with other foods – it’s an excellent source of essential vitamins and minerals that we need for healthy cells, energy and digestive function.

Now, there are exceptions to every rule, including eating fruit alone.

Blending (think smoothies) “pre-digests” the ingredients, so fruit can be combined with other nutrients in smoothies, such as healthy fats from hemp hearts, chia seeds, avocado or plant protein.

So, why not get your daily fruit fix with a green smoothie each morning? One of my favorites is this Red Velvet Smoothie.

2. Pair Protein with Non-Starchy Vegetables

We’ve already covered the basics of protein digestion, so I’ll keep it short and sweet here.

As you now know, in order to be digested, protein needs an acidic environment, which is why it’s considered a bad food combination to eat protein with starches.

However, protein can be paired with leafy greens and other high-water-content vegetables, such as asparagus, peppers, celery or broccoli.

Since these vegetables are rich in their own enzymes, they don’t require an alkaline environment for digestion.

As a result, they don’t interfere with the acidic environment required by protein.

Good protein combinations include:

•Wild salmon + broccoli + green beans

•Organic chicken + sauteed kale + mashed cauliflower

•Organic ground turkey + sauteed bell peppers, onions and swiss chard

Now, we’ve mostly talked about animal protein, but the same food combining rules apply to plant proteins, such as beans and legumes.

While I don’t typically recommend including soy products in your diet, all plant proteins follow the same food combining rules as animal protein.

3. Pair Starches with Healthy Fats and Vegetables

Asian Quinoa Mason Jar Salad

Starches (like brown rice and quinoa), along with starchy vegetables (such as sweet potatoes and squash), need an alkaline environment for digestion.

For this reason, starches combine best when eaten together – for example, brown rice or quinoa and sweet potatoes. Since non-starchy vegetables and leafy greens are considered neutral, they can also combine well with starches.

But wait … aren’t beans and legumes considered a starch?

Beans and legumes are a trickier food to categorize under food combining rules because they contain both protein and starch, which in itself is an improper food combination.

But since they’re primarily considered a starch, it’s suggested beans and legumes digest best with vegetables and other starches, such as brown rice.

Proper food combining with starches would look like:

•Quinoa + avocado + ½ baked potato drizzled with organic butter

•Lentil soup with vegetable broth + mixed veggies

•Homemade yam fries + olive oil + parsley

•Brown rice bowl + veggies sauteed in coconut oil + vegetable broth

4. Leafy Greens and Non-Starchy Vegetables Go with Everything

As we covered earlier, leafy greens and non-starchy vegetables contain their own digestive enzymes, and can be paired with any food combination without causing a traffic jam in your GI tract.

Now, if you want to be methodical with your food combining, you could eat your  leafy greens first before moving on to the rest of your plate.

This is because leafy greens digest quicker than proteins, starches and fats. But unlike fruit, they aren’t high enough in natural sugars to create a major GI tract traffic jam.

So when in doubt about food combining rules, simply choose to eat a single macronutrient (a protein, starch or healthy fat) with a leafy green or non-starchy vegetable.

5. Drink Water Away From Meals

Another food combining rule for better digestion is to avoid drinking large sips of cold water with your meals.

Water can dilute your digestive fluids, which can slow down digestion. Instead, it’s best to have small sips of room temperature water with your meals, and focus on drinking the majority of your daily water intake away from meals.

You can support your overall digestive process by drinking a glass of lemon water roughly 20 minutes before a meal. Lemon contains ascorbic acid, which can help stimulate digestion.

If you want to take your digestive function to the next level, you may also want to add a teaspoon of apple cider vinegar to your lemon water, like with this Hawaiian Apple Cider Vinegar Drink.

Apple cider vinegar is so beneficial to digestion because it contains acetic acid.  Acetic acid mimics stomach acid, which is why it can help improve poor or weakened digestion. Acetic acid has also been shown to improve calcium and magnesium absorption (3).

6. Spices, Herbs and Citrus Are Neutral

Spices and herbs like ginger, garlic, turmeric, apple cider vinegar, mustard, curry powder – along with and citrus fruits such as lemon and lime – are all considered neutral. They form proper food combinations when paired with a protein, fruit, starch or healthy fat.

Any spice or herb can be used to jazz up your favorite recipes, such as ginger in your Detox Green Juices, or lemon and apple cider vinegar on your Detox Greens Salad.



Section C

Redefining Nutrition Science

Am J Clin Nutr. 2009 May;89(5):1543S-1548S. doi: 10.3945/ajcn.2009.26736B. Epub 2009 Mar 11.

Food synergy: an operational concept for understanding nutrition.

Jacobs DR Jr1, Gross MD, Tapsell LC.

Author information


Research and practice in nutrition relate to food and its constituents, often as supplements. In food, however, the biological constituents are coordinated. We propose that “thinking food first”‘ results in more effective nutrition research and policy. The concept of food synergy provides the necessary theoretical underpinning. The evidence for health benefit appears stronger when put together in a synergistic dietary pattern than for individual foods or food constituents. A review of dietary supplementation suggests that although supplements may be beneficial in states of insufficiency, the safe middle ground for consumption likely is food. Also, food provides a buffer during absorption. Constituents delivered by foods taken directly from their biological environment may have different effects from those formulated through technologic processing, but either way health benefits are likely to be determined by the total diet. The concept of food synergy is based on the proposition that the interrelations between constituents in foods are significant. This significance is dependent on the balance between constituents within the food, how well the constituents survive digestion, and the extent to which they appear biologically active at the cellular level. Many examples are provided of superior effects of whole foods over their isolated constituents. The food synergy concept supports the idea of dietary variety and of selecting nutrient-rich foods. The more we understand about our own biology and that of plants and animals, the better we will be able to discern the combinations of foods, rather than supplements, which best promote health.

Synergy within each Plant-Food

There are thousands of phytochemicals that will never make it onto the side of a cereal box, but may play a role in reducing the risk of chronic diseases—and that’s just the ones we know about. We know whole plant foods have consistently been found to be protective. And, so, it’s reasonable for scientists to try to find the “magic bullet” active ingredient to sell it in a pill.

But, “pills…simply cannot mimic this balanced natural combination of phytochemicals present in fruits and vegetables.”

When isolated out, the compound may lose its activity, or behave differently. The antioxidant and anticancer activities of plant foods is thought to derive from the additive or synergistic effects—meaning the whole may be greater than the sum of its parts. This helps explain why a pill simply cannot replace the complex interaction of phytochemicals present in whole plant foods.

As T. Colin Campbell has pointed out, more than a hundred trials “overwhelmingly show no long-term benefit of vitamin supplements, along with worrisome findings that certain [supplements] may even increase [risk] for diabetes, heart disease, and cancer.” 

Supplementation with fish oil appears useless or worse; yet, the science doesn’t seem to matter. People continue to buy it. “The public desire for quick fixes through pills…is overwhelming, especially when money can be made.”

Synergy between and among Plant Foods

Each plant has thousands of different phytochemicals, and each plant has a whole different phytonutrient profile. And so, there may be synergistic effects when consuming different foods together, as well. Just like eating beta-carotene in carrot form is more beneficial than in pill form, because of all the other compounds in the carrot that may synergize with the beta-carotene, when you dip that carrot in hummus, all of a sudden you have the thousands of carrot compounds mixing with the thousands of chickpea compounds. And, that’s what this study was all about. What happens if you mix different fruits, with different vegetables, with different beans?

Combining foods between different categories did indeed increase the likelihood of synergy. For example, here’s the antioxidant power of raspberries alone. And, here’s the antioxidant activity of adzuki beans alone. So, if there was strictly an additive effect, the expected combination would come up to here. But, the observed antioxidant power of the combination came out more than either eaten alone.

What about anticancer effects? What if you repeated this study, but this time tried dripping different combinations of foods on breast cancer cells growing in a petri dish? Sometimes, you can get the same synergistic effects.

Here’s what grapes can do to breast cancer cells—suppressing their growth about 30%. But, onions worked even better—cutting breast cancer growth in half. Now, if you added half of each together, right, you’d assume you’d get somewhere in the middle between the two; they’d average each other out. But, instead, the researchers got this—suppressing cancer cell growth by up to like 70%.

So, the whole plus the whole was greater than the sum of the whole parts. So, did they recommend people eat a variety of foods? Maybe, add some raisins along with some chopped red onion to your next salad?

Synergy among Plant and Animal Foods

Nutr Cancer. 2014;66(6):1077-82. doi: 10.1080/01635581.2014.927687. Epub 2014 Jul 18.

Untold nutrition.

Campbell TC1.

Author information


Nutrition is generally investigated, and findings interpreted, in reference to the activities of individual nutrients. Nutrient composition of foods, food labeling, food fortification, and nutrient recommendations are mostly founded on this assumption, a practice commonly known as reductionism. While such information on specifics is important and occasionally useful in practice, it ignores the coordinated, integrated and virtually symphonic nutrient activity (wholism) that occurs in vivo. With reductionism providing the framework, public confusion abounds and huge monetary and social costs are incurred. Two examples are briefly presented to illustrate, the long time misunderstandings (1) about saturated and total fat as causes of cancer and heart disease and (2) the emergence of the nutrient supplement industry. A new definition of the science of nutrition is urgently needed.

PMID: 25036857 DOI: 10.1080/01635581.2014.927687

[Indexed for MEDLINE]

Holism Versus Reductionism or Isolationism

Nutrition is generally investigated, and findings interpreted, in reference to the activities of individual nutrients. Nutrient composition of foods, food labeling, food fortification, and nutrient recommendations are mostly founded on this assumption, a practice commonly known as reductionism.

While such information on specifics is important and occasionally useful in practice, it ignores the coordinated, integrated and virtually symphonic nutrient activity (wholism) that occurs in vivo.

With reductionism providing the framework, public confusion abounds and huge monetary and social costs are incurred.

Two examples are briefly presented to illustrate, the long time misunderstandings (1) about saturated and total fat as causes of cancer and heart disease and (2) the emergence of the nutrient supplement industry.

A new definition of the science of nutrition is urgently needed.

Campbell TC. Untold nutrition. Nutr Cancer. 2014;66(6):1077-82.

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Am J Clin Nutr. 2003 Sep;78(3 Suppl):517S-520S.

Health benefits of fruit and vegetables are from additive and synergistic combinations of phytochemicals.

Liu RH1.

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Cardiovascular disease and cancer are ranked as the first and second leading causes of death in the United States and in most industrialized countries. Regular consumption of fruit and vegetables is associated with reduced risks of cancer, cardiovascular disease, stroke, Alzheimer disease, cataracts, and some of the functional declines associated with aging.

Prevention is a more effective strategy than is treatment of chronic diseases. Functional foods that contain significant amounts of bioactive components may provide desirable health benefits beyond basic nutrition and play important roles in the prevention of chronic diseases.

The key question is whether a purified phytochemical has the same health benefit as does the whole food or mixture of foods in which the phytochemical is present.

Our group found, for example, that the vitamin C in apples with skin accounts for only 0.4% of the total antioxidant activity, suggesting that most of the antioxidant activity of fruit and vegetables may come from phenolics and flavonoids in apples.

We propose that the additive and synergistic effects of phytochemicals in fruit and vegetables are responsible for their potent antioxidant and anticancer activities, and that the benefit of a diet rich in fruit and vegetables is attributed to the complex mixture of phytochemicals present in whole foods.


Liu RH. Health benefits of fruit and vegetables are from additive and synergistic combinations of phytochemicals. Am J Clin Nutr. 2003 Sep;78(3 Suppl):517S-520S.

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J Nutr. 2004 Dec;134(12 Suppl):3479S-3485S.

Potential synergy of phytochemicals in cancer prevention: mechanism of action.

Liu RH1.

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Epidemiological studies have consistently shown that regular consumption of fruits and vegetables is strongly associated with reduced risk of developing chronic diseases, such as cancer and cardiovascular disease. It is now widely believed that the actions of the antioxidant nutrients alone do not explain the observed health benefits of diets rich in fruits and vegetables, because taken alone, the individual antioxidants studied in clinical trials do not appear to have consistent preventive effects.

Work performed by our group and others has shown that fruits and vegetable phytochemical extracts exhibit strong antioxidant and antiproliferative activities and that the major part of total antioxidant activity is from the combination of phytochemicals. 

We proposed that the additive and synergistic effects of phytochemicals in fruits and vegetables are responsible for these potent antioxidant and anticancer activities and that the benefit of a diet rich in fruits and vegetables is attributed to the complex mixture of phytochemicals present in whole foods.

This explains why no single antioxidant can replace the combination of natural phytochemicals in fruits and vegetables to achieve the health benefits. The evidence suggests that antioxidants or bioactive compounds are best acquired through whole-food consumption, not from expensive dietary supplements.

We believe that a recommendation that consumers eat 5 to 10 servings of a wide variety of fruits and vegetables daily is an appropriate strategy for significantly reducing the risk of chronic diseases and to meet their nutrient requirements for optimum health.


Liu RH. Potential synergy of phytochemicals in cancer prevention: mechanism of action. J Nutr. 2004 Dec;134(12 Suppl):3479S-3485S.

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J Agric Food Chem. 2011 Feb 9;59(3):960-8. doi: 10.1021/jf1040977. Epub 2011 Jan 11.

Synergistic, additive, and antagonistic effects of food mixtures on total antioxidant capacities.

Wang S1, Meckling KA, Marcone MF, Kakuda Y, Tsao R.

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Different foods possess different bioactive compounds with varied antioxidant capacities. When foods are consumed together, the total antioxidant capacity of food mixtures may be modified via synergistic, additive, or antagonistic interactions among these components, which may in turn alter their physiological impacts.

The main objective of this study was to investigate these interactions and identify any synergistic combinations.

Eleven foods from three categories, including fruits (raspberry, blackberry, and apple), vegetables (broccoli, tomato, mushroom, and purple cauliflower), and legumes (soybean, adzuki bean, red kidney bean, and black bean) were combined in pairs.

Four assays (total phenolic content, ferric reducing antioxidant power, 2,2-diphenyl-1-picrylhydrazyl, radical scavenging capacity, and oxygen radical absorbance capacity) were used to evaluate the antioxidant capacities of individual foods and their combinations. The results indicated that within the same food category, 13, 68, and 21% of the combinations produced synergistic, additive, and antagonistic interactions, respectively, while the combinations produced 21, 54, and 25% synergistic, additive, and antagonistic effects, respectively, across food categories.

Combining specific foods across categories (e.g., fruit and legume) was more likely to result in synergistic antioxidant capacity than combinations within a food group.

Combining raspberry and adzuki bean extracts demonstrated synergistic interactions in all four chemical-based assays.

Compositional changes did not seem to have occurred in the mixture. Results in this study suggest the importance of strategically selecting foods or diets to maximum synergisms as well as to minimum antagonisms in antioxidant activity.

PMID: 21222468 DOI: 10.1021/jf1040977

Wang S, Meckling KA, Marcone MF, Kakuda Y, Tsao R. Synergistic, additive, and antagonistic effects of food mixtures on total antioxidant capacities. J Agric Food Chem. 2011 Feb 9;59(3):960-8.

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J Med Food. 2013 Dec;16(12):1138-45. doi: 10.1089/jmf.2013.0051.

Antioxidant capacity of food mixtures is not correlated with their antiproliferative activity against MCF-7 breast cancer cells.

Wang S1, Zhu F, Meckling KA, Marcone MF.

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Combining different foods may produce additive, synergistic, or antagonistic interactions that may modify certain physiological effects (i.e., anticancer properties). For investigating these interactions and potential synergetic combinations, thirteen foods from three categories, including fruits (raspberries, blackberries, apples, grapes), vegetables (broccoli, tomatoes, mushrooms, purple cauliflowers, onions), and legumes (soy beans, adzuki beans, red kidney beans, black beans), were evaluated for their inhibitory activity against MCF-7 breast cancer cells. Grape, onion, and adzuki bean showed maximal growth inhibition of MCF-7 from the fruit, vegetable, and legume groups, respectively. When these three foods were combined in pairs, unique interactions were observed that were not seen when individual extracts were used. Combining onion and grape resulted in a synergistic antiproliferative effect (APE) against MCF-7 compared with either onion or grape treatment alone. In contrast, combining grape and adzuki bean resulted in an antagonistic interaction. Additionally, four antioxidant assays (total phenolic contents, ferric reducing antioxidant power, 2,2-diphenyl-1-picrylhydrazyl, and oxygen radical absorbance capacity) were further used to evaluate the antioxidant capacities (AC) of individual foods and their combinations. Combining raspberry and adzuki bean extracts demonstrated synergistic AC in all four assays, but they did not show synergistic APE against the MCF-7 cells. Combining broccoli and soy produced antioxidant antagonism, but did not have an antagonistic APE against MCF-7. The synergistic or antagonistic AC of food mixtures did not correlate with the synergistic or antagonistic APE against MCF-7. Further investigation is to determine the mechanisms of these interactions and to predict and enhance the therapeutic benefits of foods and food components through strategic food combinations.

PMID: 24328703 DOI: 10.1089/jmf.2013.0051


Wang S, Zhu F, Meckling KA, Marcone MF. Antioxidant capacity of food mixtures is not correlated with their antiproliferative activity against MCF-7 breast cancer cells. J Med Food. 2013 Dec;16(12):1138-45.

Acute combined effects of olive oil and wine on pressure wave reflections: another beneficial influence of the Mediterranean diet antioxidants?

Papamichael, Christos Ma; Karatzi, Kalliopi Na,b; Papaioannou, Theodore Ga; Karatzis, Emmanouil Na; Katsichti, Paraskevia; Sideris, Vasilisa; Zakopoulos, Nikolaosa; Zampelas, Antonisc; Lekakis, John Pa

Journal of Hypertension: February 2008 – Volume 26 – Issue 2 – p 223–229

doi: 10.1097/HJH.0b013e3282f25b80

Original papers: Diet


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Objectives: Combined consumption of olive oil and wine is common in the Mediterranean diet, but there are no data concerning their synergistic haemodynamic response. We sought to determine the combined postprandial effects of wine and olive oil on wave reflections and central haemodynamics.

Methods: Fifteen healthy subjects consumed four standard meals on different days, containing 50 g of olive oil and 250 ml of wine, in a randomized cross-over study design. Two types of wine [red (R) and white (W)] and two types of olive oil [green (G) and refined (O) (rich and poor in antioxidants, respectively)] were used in all possible combinations (RO, RG, WO and WG). Applanation tonometry and aortic pulse wave analysis were performed when fasting and 1, 2 and 3 h postprandially. A second group of 15 healthy individuals matched for age, gender and body mass index served as the control group.

Results: All meals decreased AIx (RO and RG, P < 0.001; WO, P = 0.007; and WG, P = 0.039). The AIx reduction after RG, RO, WO and WG was significantly different from the respective AIx response of the control group. No difference was observed in the reduction of AIx between sessions, but a significantly earlier peak decrease in AIx, as well as a more prolonged decreasing effect, was observed after RG and RO consumption compared to WO and WG. Central systolic and diastolic pressures were diminished after all four combinations of wine and olive oil (P < 0.05).

Conclusions: Combined consumption of wine and olive oil provided beneficial postprandial effects on haemodynamics. These findings reveal an additional favourable effect of components of the Mediterranean diet on haemodynamics in the postprandial state.

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