The Metabolic Matrix: Re-engineering ultraprocessed foods to feed the gut, protect the liver, and support the brain.
The Metabolic Matrix methods article (Harlan et al., 2023) proposes three key pillars – Support the Brain, Protect the Liver, and Feed the Gut – and serves as a novel guide to reengineering ultraprocessed foods in favor of improving metabolic health. The liver is a vital organ which plays a critical role in metabolism and in the storage, secretion, and detoxification of internal and external substances (Mega et al., 2021). There are 1-3 million xenobiotics, i.e., chemical substances, foreign to plant and animal life which gain access to the human body during the lifespan, and which may prove to be toxic. The liver plays a key role in preventing toxic liver damage from many of these substances and nutrition, is hypothesised to protect from a multitude of injuries which may lead to chronic liver disease and cirrhosis (Mega et al., 2021). The component Protect the Liver is detailed in our recently published methods paper and focused on 5 elements related to metabolic health namely: (i) reducing fructose and (ii) total sugar intake, (iii) ensuring adequate hydration, (v) minimising environmental toxins and (vi) reducing glycemic load.
This section aims to address questions concerning why our scientific team specifically selected the concept of protecting the liver.
Other sections of the website address the other two elements of the triage, Feed the Gut and Support the Brain.
The premature development of chronic disease may include non-alcoholic fatty liver disease which has risen exponentially throughout both the developed and developing world. In fact, NAFLD affects around 35% of North Americans alone (Le et al., 2022) and approximately 80% of individuals with metabolic syndrome (Bence & Birnbaum, 2021). A key driver is insulin resistance independent of aging. Non-alcoholic fatty liver disease (NAFLD) is a build-up of fat which can cause abnormal enlargement of the liver. In many cases there are no obvious symptoms of NAFLD. However, when symptoms are present, the patient can experience weight loss, fatigue, yellowing of the skin and eyes, pain in the upper right abdomen, fluid and swelling in the stomach and legs. Anyone experiencing any of these symptoms is advised to visit a doctor as soon as possible for examination. Individuals with NAFLD are at increased risk of obesity, type 2 diabetes (T2D), cardiovascular disease (CVD), and premature death (Wang et al., 2021).
The precise causes of NAFLD are inconclusive although there are some robust risk factors. These include a poor lifestyle (e.g., unhealthy eating patterns and sedentary behaviour), obesity, type 2 diabetes, and metabolic syndrome. Genes, diet, specific health conditions and the digestive system all play a role and interact together. Biomarkers can be assessed by your general health care practitioner and include high cholesterol, high triglycerides, excess consumption of fructose and altered gut microbiome. Excess sugar is thought to be a major mediator in the development of NAFLD (Jensen et al., 2018). Often when NAFLD is suspected, a general health care provider will look for physical signs of insulin resistance which may include darker skin patches over part of the body such as knuckles, knees, and elbows as well as signs of cirrhosis such as ascites and/or muscle loss. NAFLD is typically diagnosed when elevated levels of liver enzymes are discovered typically via a blood test.
There are several tests which are used to assess excess fat in the liver including an ultrasound and a transient elastography which measures stiffness in the liver. The more pronounced the stiffness the great the scarring. In some case a biopsy of the liver is conducted and examined in a laboratory for inflammation and scarring. It is critical that the liver is assessed for cirrhosis which hinders the ability of the liver to complete its function. Cirrhosis cannot be reversed but it must be slowed down or stopped to avoid complete liver failure. The only option for liver failure is a liver transplant. In addition, untreated cirrhosis may lead to liver cancer.
In a healthy person, the liver serves to remove toxins from the body. It creates a type of bile made from protein which metabolises fat into fatty acids which are then digested.
It is important to improve your lifestyle when living with NAFLD. This includes eating a nutrient-dense diet rich in polyunsaturated fatty acids from healthy assortment of whole grains, legumes, fish, olive oils, nut, seeds, fruits, and green, leafy vegetables. Exercising on a regular basis, calorie (food portion) reduction and losing weight if overweight. It is important to avoid alcohol intake and avoid added sugars, refined carbohydrates, saturated fat, processed foods, and industrially produced seed oils. Adopting a healthier lifestyle can also help manage and in some instances, reverse, other metabolic symptoms such as obesity, high blood pressure, cholesterol levels and type 2 diabetes.
There are a range of healthy foods and nutrients which may help prevent and manage NAFLD. Some of these include omega-3 fatty acids from wild fish and seafood (e.g., wild Alaskan salmon, sardines, Rainbow trout, mackerel) which may help reduce liver fat, elevate protective HDL cholesterol and reduce triglycerides (Lu et al., 2016; Scorletti & Byrne, 2013). Omega-3 fatty acids also reduce inflammation (DiNicolantonio & O’Keefe, 2018) and everyone should be eating an least 2 portion of oily fish every week. Omega-3 fish oil is thought to help maintain insulin signalling in the brain, ameliorate NAFLD and decrease risk of metabolic syndrome (Simopoulos, 2013).
Other nutrients which are thought to be protective in liver health including specific vitamins such as Vitamins B, C, D and E. The antioxidant, Vitamin E which can be sourced from sunflower seeds (20 mg of Vitamin E per 100 grams of sunflower seeds) is particularly beneficial to individuals with NAFLD (El Hadi et al., 2018; Sato et al., 2015). High fiber foods such as oats are also considered beneficial for individuals with NAFLD and may help reduce high triglycerides (Rosqvist et al., 2020).
Nuts and seeds may help lower inflammation, reduce oxidative stress and lower levels of insulin resistance (Zhang et al., 2019). Other foods which are thought to specifically modify the trajectory of NAFLD include coffee, tea, red wine, avocado and olive oil. All these foods may be helpful in terms of weight loss and a reduction in body weight is linked to a reduction in haptic inflammation of steatosis (fatty liver disease) (Gupta et al., 2015). The active ingredient in turmeric is called curcumin and supplementation is thought potentially useful to reduce biomarkers of liver damage in patients with NALFD. For example, there are 2 enzymes called serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) which are elevated in patients with fatty liver disease. Supplementation with turmeric (the bright orange root which is available in powdered form) has been found in recent meta-analytic studies to help decrease levels of both AST and ALT in patients with NAFLD (Goodarzi et al., 2019).
More recently, a study published in the journal, Nature found that higher yoghurt consumption was negatively correlated with the presence of newly diagnosed NAFLD, possibly due to the presence and delivery of abundant probiotics (live cultures) to the gastrointestinal tract (Zhang et al., 2020).
Garlic is considered to be beneficial to overall human health and in particular its consumption in linked to reduced body weight, reductions in liver fat and has been negatively associated with NAFLD in Chinese men (Sangouni et al., 2020; Soleimani et al., 2020).
Which Foods to Avoid
The Metabolic Matrix is a framework and guide for metabolic health and disease prevention. There are specific foods and beverages which should be avoided especially in the case of NAFLD. These include alcohol, sweetened beverages, added sugar (excess sugar results in the accumulation of fat in the liver), processed, refined, and fried foods (Zhang et al., 2022), added salt (da Silva Ferreira et al., 2023), red and processed meats (Rahimi-Sakak et al., 2022) and white pasta, bread and rice.
Role of Fructose and Sugar in NAFLD
Recent evidence has suggested that excess dietary sugar from either sucrose and/or high-fructose corn syrup (HFCS) increases risk for NAFLD (Jensen et al., 2018). This association is indeed a key area of research focus and the relationship is thought to be driven not by the fructose molecule itself, but via the accumulation of fat in the liver by the simultaneous blocking of fatty acid oxidation and the activation of lipogenesis (Lanaspa, Cicerchi, et al., 2012; Lanaspa, Sanchez-Lozada, et al., 2012). Additionally, poor gut health including alterations to gut permeability, endotoxins and microbiome all play a role. Current dietary recommendations are to significantly lower and restrict sugar and total fructose intake
Ensuring Healthy Hydration
It has long been known that the liver cells require adequate hydration to function normally and that deviation from hydration changes rapidly within minutes under the influence of hormones, nutrition, oxidative stress and iso-osmotic concentration (Häussinger et al., 1997). Water is critical for nutrient transport throughout the body and dehydration can result in reduced liver function. Water helps dissolve fats and soluble fiber, prevent constipation, reduces the burden on the kidneys and helps the liver remove waste from the body. A recent study reported that plain drinking water (as opposed to soft drinks and other sweetened beverages) may be protective against the development of NAFLD (Wang et al., 2021).
There are a range of environmental risk factors implicated in liver disease (Sarin et al., 2020). Some of these include cigarette smoking, alcohol consumption and viral infections such as hepatitis B and C (Melaram, 2021). Recent research interest has focused on the role of specific environmental toxins such as pesticides, aflatoxins (e.g., fungal contamination in dried foods, spices, tree nuts etc) and microcystins (i.e., these are highly toxic caused by various strains of certain fresh water cyanobacteria and found in the environment) in liver disease (Melaram, 2021). Minimising environmental toxins which includes random ingredient testing by a reputable organization is critical to reduce toxic exposure.
Reducing glycemic load
Both the dietary glycaemic Index (GI) and glycaemic load (GL) has been hypothesised as a robust predictor of NAFLD progression (Perumpail et al., 2017; Zelber-Sagi et al., 2016). Increasing research, including several meta-analytic and systematic reviews have reported evidence to suggest that reducing glycemic load may reduce liver disease and hepatic liver mass especially in adult patients with NAFLD (Parker & Kim, 2019) and children (Mager et al., 2015). In a small study of 17 obese children with fatty liver disease, participants were randomly allocated to receive an experimental low gylcemic load or conventional low-fat diet for 6 months. The authors found that moderate weight loss on either a low-GL or low-fat diet produced clinically meaningful improvement in liver fat within 6 months (Ramon-Krauel et al., 2013). Additional research is warranted to assess whether these results can be replicated in larger cohorts of both children and adults with NAFLD.
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