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The role of diet in the development of MGUS, smoldering myeloma and multiple myeloma

A 2018 study done in Reykjavic, Iceland found that intake of fruit at least three times per week during adolescence was associated with lower risk of MGUS when compared to lower fruit consumption. Intake of fruit at least three times per week during the late life period was associated with decreased risk of progressing from MGUS to multiple myeloma (MM). Studies such as this suggest that diet might alter the risk of developing MGUS and progression to MM.

The possible causes of multiple myeloma and its precursor diseases (MGUS and SMM) are many and most have, at present, not been definitively established. Thus it is difficult to advise on prevention strategies. Most established risk factors are not modifiable. In fact, obesity is considered the first and only modifiable risk factor for MM. Obesity, which is characterized by higher amounts of fatty tissue, is associated with higher levels of proinflammatory compounds in the body – called cytokines (such as c-reactive protein [crp]) and endogenous growth factors (such as insulin-like growth factor-1 [IFG-1] and interleukin -6 [IL-6]). These are measured in the blood. New research shows that inflammation and endogenous growth factors, such as these mentioned, play an important role in the development of MM. Even in lean individuals, research is showing that there is a strong positive association between inflammatory or insulinemic diets and MM risk.

In studies of the association between dietary pattern and multiple myeloma incidence, it has been observed that diets that lead to high insulin (a hormone which allows your body to use sugar) secretion, insulin resistance and high biomarkers of inflammation may cause or contribute to the development of MM. Plausible biological mechanisms link diet and MM, for example, inflammation and endogenous growth factors are important in MM cell growth, proliferation and survival and they promote a physiologic environment favourable to disease progression.

The study of dietary pattern as a risk factor has advantages over the study of individual foods or nutrients because dietary pattern accounts for additive, interactive, or synergistic effects of multiple foods and nutrients and makes it easier to advise on clinical and public health recommendations.

Clinical research studies have shown that adherence to healthier dietary patterns show lower levels of biomarkers of inflammation (e.g., CRP, IL-6) and insulin response (e.g., fasting insulin), while adherence to unhealthy dietary patterns show higher biomarkers of inflammation and insulin response. The research findings suggest that dietary patterns may play a role in the development and progression of multiple myeloma.

There are a number of dietary patterns (also called diet quality indices which are mathematical algorithms) that have been developed to evaluate the healthfulness of individual diets. Below is a summary of the dietary patterns, both healthy and unhealthy:

Healthy eating patterns:

AHEI – alternate healthy eating index

This dietary pattern is associated with a lower risk of many chronic illnesses -diabetes, cardiovascular disease and cancer - in both men and women. A higher AHEI diet score reflects a high intake of whole grains, polyunsaturated fatty acids (such as sunflower seeds and salmon), nuts and long chain omega-3 fats (such as edamame, seaweed and kidney beans) and low intakes of red/processed meats, refined grains and sugar sweetened drinks.

aMED – alternate Mediterranean diet

aMED is a plant based way of eating based on the traditional cuisine of countries bordering the Mediterranean Sea. The aMED diet was created to help balance cholesterol levels through the inclusion of healthy fatty acids (healthy fats are a mainstay of the Mediterranean diet) from sources such as nuts, fish, and olive oil. While there is no single definition of the Mediterranean diet, it is typically high in vegetables, fruits, whole grains, beans, nut and seeds, and olive oil; weekly intake of fish, poultry, beans and eggs; moderate portions of dairy products; limited intake of red meat. Fatty fish — such as mackerel, herring, sardines, albacore tuna, salmon and lake trout -are important in the Mediterranean diet.

Other important elements of the Mediterranean diet are sharing meals with family and friends, enjoying a glass of red wine and being physically active.

DASH – dietary approaches to stop hypertension

Dash is an eating plan that is based on research studies sponsored by the National Heart, Lung, and Blood Institute (NHLBI). These studies showed that DASH lowers high blood pressure and improves levels of cholesterol. The diet is simple: Eat more fruits, vegetables, and low-fat dairy foods, cut back on foods that are high in saturated fat, cholesterol, and trans fats, eat more whole-grain foods, fish, poultry, and nuts , limit sodium, sweets, sugary drinks, and red meats. In research studies, people who were on the DASH diet lowered their blood pressure within 2 weeks.

PRUDENT dietary pattern

The “Prudent” dietary pattern is characterized by a high intake of fruit, vegetables, fish, and whole grain cereals.

Unhealthy eating patterns

Other dietary patterns are indicative of unhealthy dietary choices. These include the “Western” pattern diet, EDIH (empirical dietary index for hyperinsulinemia), EDIP (empirical dietary inflammatory pattern), EDIR (empirical dietary index for insulin resistance).

The Western Pattern Diet (WPD) - also known as the Standard American Diet (SAD) is a modern-day style diet that mostly contains high amounts of processed foods, red meat, high-fat dairy products, high-sugar foods, and pre-packaged foods, that increase the risk of chronic illness.

EDIH (empirical dietary index for hyperinsulinemia) - was derived to identify food groups that most contribute to hyperinsulinemia (using the triglyceride to HDL cholesterol ratio as a marker). This includes red meat, processed meat, cream soups, margarine, butter, French fries, sugar-sweetened beverages, poultry and eggs. The resulting nutrient profile is rich in total and saturated fat, cholesterol and total protein, and low in fibre and total carbohydrates.

EDIP – (The empirical dietary inflammatory pattern) score was derived to identify food groups most predictive of 3 markers of inflammation (interleukin-6, C-reactive protein, and tumor necrosis factor-alpha receptor).

Foods to avoid on an anti-inflammatory diet are: processed foods, foods with added sugar or salt, unhealthful oils, processed carbs which are present in white bread, white pasta, and many baked goods, processed snack foods, such as chips and crackers, premade desserts, such as cookies, candy, and ice cream, excess alcohol.

EDIR (empirical dietary index for insulin resistance) was derived to identify food groups most predictive of hyperinsulinemia (measure in the blood by C-peptide; C-peptide and the hormone insulin are created from a larger molecule called proinsulin and stored in the beta cells of the pancreas. When insulin is released into the bloodstream to help transport glucose into the body's cells (to be used for energy), equal amounts of C-peptide also are released. This makes C-peptide useful as a marker of insulin production.). The C-peptide dietary pattern is characterized by higher meat, non-fatty fish, sweetened beverage intake, high fat dairy, and lower coffee and whole grains intake.

Higher EDIH, EDIR, and EDIP scores have been found to be strong predictors of inflammation, insulin resistance and hyperinsulinemia and these dietary patterns have been shown to influence chronic disease development and outcome. Such diseases include cardiovascular disease, diabetes, dementia, various cancers including colorectal cancer and other cancers of the gastrointestinal tract. Research is now showing that these dietary patterns are also playing a role in the development of multiple myeloma.

In addition to playing a role in the development of MM, studies with MM patients having healthier prediagnosis (which includes patients with MGUS/SMM) dietary patterns had superior survival to those with less healthy diets regardless of the year of MM diagnosis. Specifically, higher prediagnosis AHEI, aMED, DASH and Prudent pattern scores and lower prediagnosis Western pattern, EDIR and EDIH scores were significantly associated with lower MM-specific and all-cause mortality in MM patients. These findings provide evidence that healthy prediagnosis dietary habits may offer survival benefits among MM patients even in the era of more advanced therapies which have emerged for MM treatment in the past two decades. These dietary patterns complement these advanced therapies.

The above shows that there is a relationship between diet and the risk of MM, and also a relationship between diet and prognosis of patients with MM.

Taken together with our curcumin studies which have shown that this supplement may stabilise or improve markers of disease progression, MGUS/SMM patients can now be proactive in managing their disease. A change in diet together with evidence based supplements can slow or stop disease progression. Such is the interest in dietary change and the potential role of curcumin in slowing this disease, that 2 new clinical trials are currently being undertaken in MGUS/SMM patients:

1: Clinical trial number NCT04920084 – the NUTRIVENTION study conducted by Dr Urvi Shah from Memorial Sloan Kettering Cancer Centre.

2: Clinical trial number NCT04731844 – a curcumin plus piperine study conducted by Dr Peter Van Veldhuizen from the University of Rochester.

The results from both these studies are eagerly awaited!!

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