While a diet high in vegetables, fruits and dietary fiber, as well as dietary intake of lutein, zeaxanthin, zinc and polyunsaturated fatty acids including linoleic acid may decrease the risk of Non-Hodgkin Lymphoma, following a diet high in animal protein, fats and dairy products may increase the risk of Non-Hodgkin Lymphomas such as Diffuse Large B Cell Lymphoma (DLBCL). Different studies found Vitamin D insufficiency as a key factor for clinical failures in Non-Hodgkin lymphoma patients, indicating that the use of Vitamin D supplements in these patients with Vitamin D deficiency may be a potential strategy to improve treatment/clinical outcomes, though clinical studies are needed to confirm the same. Also, while the intake of Selenium and Vitamin C supplements may have certain benefits in Non-Hodgkin lymphoma patients undergoing cancer treatment, dietary intake of nitrate and nitrite may not help.
What is Lymphoma?
Lymphoma is the cancer of the lymphatic system that begins in lymphocytes, the infection-fighting white blood cells in the immune system. The lymphatic system includes the spleen, thymus, bone marrow, lymph nodes, adenoids and tonsils, and lymphocytes. There are more than 90 different subtypes of lymphomas.
Cancers of the lymphatic system are traditionally classified into two.
- Hodgkin’s lymphoma
- Non-Hodgkin’s lymphoma
Among these, Non-Hodgkin Lymphoma is the most prevalent.
A lymphoma is classified as Hodgkin’s lymphoma if there is a presence of an abnormal cell called the Reed-Sternberg cell. The Reed-Sternberg cell is a B cell/B lymphocyte that has become cancerous. If the Reed-Sternberg cell is not present, the lymphoma is classified as Non-Hodgkin Lymphoma.
In this blog, we will be focussing on studies associated with diet and nutrition for Non Hodgkin’s Lymphoma.
More about Non-Hodgkin Lymphoma (NHL)
According to the American Cancer Society, Non-Hodgkin Lymphoma (NHL) accounts for 4% of all the cancers in the United States and around 80% of all lymphomas. Although NHL is commonly diagnosed in adults, children can get it too.
The most common symptoms of NHL are abdominal pain or swelling, chest pain, coughing, difficulty in breathing, swollen lymph nodes, fatigue, fever, night sweats and weight loss.
Different Types of NHL
The type of Non-Hodgkin Lymphoma depends on various factors including :
- Type of lymphocyte affected (B cells or T cells)
- How quickly the cancerous cells grow and spread
Examples of some of the different types of Non-Hodgkin Lymphoma include:
- B-Cell Chronic Lymphocytic Leukemia/Small Lymphocytic Leukemia
- Lymphoplasmacytic Lymphoma
- Mantle Cell Lymphoma
- Follicular Lymphoma
- Marginal Zone B-Cell Lymphoma
- Diffuse Large B-Cell Lymphoma (DLBCL)
- Burkitt’s Lymphoma
- Burkitt’s Like Lymphoma
- Precursor B or T-Cell Lymphoblastic Lymphoma/Leukemia
- Sezary-Mycosis-fungoides T cell lymphomas
Based on the rate at which Non-Hodgkin lymphoma grows and spreads, it can either be aggressive or indolent.
Treatment for Non-Hodgkin Lymphoma
There are various types of treatments used for Non-Hodgkin Lymphoma including Radiation therapy, Chemotherapy, Immunotherapy, Targeted therapy, Plasmapheresis, Surgery and Stem cell transplantation. To decide on the treatment for Non-Hodgkin Lymphoma, it is important to find out the exact type of lymphoma, along with the stage of the cancer. However, in fast-growing lymphomas like Burkitt lymphoma, the details of the stage may be less important when deciding on the treatment.
Diet for Non-Hodgkin Lymphoma
Over the recent decades, the incidence of Non-Hodgkin lymphoma (NHL) has significantly increased. Diet may also play a key role in increasing or reducing the risk of Non-Hodgkin lymphoma and may also improve or worsen the cancer treatments and treatment side effects in NHL patients. To evaluate the association of various dietary components with the risk of Non-Hodgkin lymphoma and treatment outcomes, several observational and clinical studies have been performed by researchers across the world. Let us now zoom in to some of these clinical and observational studies.
Studies associated with Diet, Supplements and Nutritional Status in Non-Hodgkin Lymphoma Patients
Use of Selenium Supplements by Non-Hodgkin Lymphoma Patients Undergoing Chemo Treatment
Researchers from the Ain-Shams University in Cairo, Egypt evaluated data from 30 patients who were diagnosed with non-Hodgkin lymphoma to study the effect of the administration of high doses of selenium (sodium selenite) in these patients who were undergoing chemo treatment. The study found that 67% of the Non-Hodgkin lymphoma patients who received chemo treatment alone got an infection, however only 20% of the patients who received both chemo treatment and selenium supplements got an infection. (Asfour IA et al, Biol Trace Elem Res., 2006)
Impact of Vitamin D Status on Treatment Outcomes in Lymphoma Patients
Use of Vitamin D Supplements by Patients with Aggressive B-cell Lymphomas Undergoing Immunochemotherapy Treatment
In a study published in 2018, the researchers from the Università Cattolica del Sacro Cuore in Rome, Italy evaluated the impact of using Vitamin D3 supplements and 25-hydroxyvitamin D level normalization on event-free survival in patients with aggressive B-cell lymphomas who underwent R-CHOP treatment and had 25-hydroxyvitamin D deficiency. The researchers conducted the analysis in a cohort of 155 patients with aggressive B-cell lymphomas of whom 128 had diffuse large B-cell lymphoma (DLBCL). Of these, 25-hydroxyvitamin D levels were found to be deficient (<20 ng/mL) in 105 patients, insufficient (20-29 ng/mL) in 32 patients, and normal (≥30 ng/mL) in 18 patients. In 56% of 116 patients who received vitamin D3 (cholecalciferol) supplements, the levels of 25-hydroxyvitamin D were normalized. (Stefan Hohaus et al, Cancer Med., 2018)
The study found that B cell lymphoma patients with normalized 25-hydroxyvitamin D levels following use of Vitamin D3/cholecalciferol supplements showed better event-free survival than patients with persistently deficient 25-hydroxyvitamin D levels.
Association between Vitamin D Insufficiency and Clinical Failure in Follicular Lymphoma Patients
A clinical study done by the researchers from the Mayo Clinic – Rochester and University of Iowa in the United States investigated whether Vitamin D insufficiency was associated with adverse clinical outcomes among follicular lymphoma patients. For the analysis, the researchers used an observational cohort study which included a total of 642 Follicular lymphoma patients, with a mean age of 60 years at the time of diagnosis, who were enrolled between 2002 and 2012. After a mean follow-up of around 5 years, 297 patients faced disease progression or treatment failure, 78 patients died and 42 patients died due to lymphoma. (S I Tracy et al, Blood Cancer J., 2017)
The analysis of data from these lymphoma patients showed that Vitamin D insufficiency was associated with reduced event-free survival at 12 months, overall survival and lymphoma-specific survival of the full cohort of patients.
Association between Vitamin D Insufficiency and Clinical Outcomes in Chronic Lymphocytic Leukemia Patients
Another study done by the researchers from the Mayo Clinic in Rochester, US also evaluated the association of 25-hydroxyvitamin D serum levels with time-to-treatment and overall survival in 390 newly diagnosed Chronic Lymphocytic Leukemia patients who participated in a cohort study (tagged as the discovery cohort) and another cohort of 153 previously untreated patients who participated in an observational study (tagged as the validation cohort). (Tait D Shanafelt et al, Blood., 2011)
The study found that 119 CLL patients in the discovery cohort were 25-hydroxyvitamin D insufficient, with shorter time-to-treatment and overall survival after a median follow-up of 3 years. A similar trend was also found in 61 CLL patients in the validation cohort who were 25-hydroxyvitamin D insufficient. After a median follow-up of 9.9 years, time-to-treatment and overall survival were shorter for these 25(OH)D-insufficient patients. The study concluded that Vitamin D insufficiency was associated with shorter time-to-treatment and overall survival in Chronic Lymphocytic Leukemia patients. However, clinical studies are needed to confirm whether normalizing vitamin D levels by taking Vitamin D supplements in deficient CLL patients would improve their clinical outcomes.
Another recent study published in 2020 by the St. George University Hospital for Active Treatment in Bulgaria also analyzed data from 103 blood cancer patients and observed that the majority of the patients who were diagnosed with Non-Hodgkin lymphoma/diffuse large B-cell lymphoma (DLBCL), chronic lymphocytic leukemia and multiple myeloma had severe vitamin D deficiency. (Vasko Graklanov et al, J Int Med Res., 2020)
Findings from these studies indicate that using Vitamin D supplements in lymphoma patients with Vitamin D deficiency may be possibly beneficial in improving clinical outcomes.
Impact of Vitamin C Supplementation in Lymphoma Patients
Impact on Inflammation in B-Cell Lymphoma Patients
A study published in 2012 evaluated the impact of high dose intravenous Vitamin C on inflammation in 45 patients who were diagnosed with either prostate cancer, breast cancer, bladder cancer, pancreatic cancer, lung cancer, thyroid cancer, skin cancer or B-cell lymphoma. The cancer patients including lymphoma patients were administered with high doses of Vitamin C post their standard conventional treatment. (Mikirova N et al, J Transl Med. 2012)
The study found that intravenous Vitamin C significantly reduced the levels of markers which increase inflammation such as IL-1α, IL-2, IL-8, TNF-α, chemokine eotaxin and C-Reactive protein (CRP). The researchers also found that the decrease in CRP levels during Vitamin C treatment correlated with decrease in few tumor markers.
Vitamin C/Ascorbic Acid Supplementation in Relapsed B-cell Non-Hodgkin Lymphoma Patients
A phase I clinical trial done by the Tokai University School of Medicine in Japan evaluated the safety and dosage of intravenous l-ascorbic acid / Vitamin C in conjunction with chemotherapy for patients with relapsed B Cell Non-Hodgkin lymphoma. The study found that intravenous administration of Vitamin C/Ascorbic Acid at a whole body dose of 75 g may be safe and sufficient to achieve the required serum concentration. However, a phase II trial will be needed to assess the effectiveness of intravenous Vitamin C/Ascorbic Acid administration in relapsed/refractory lymphoma patients.(Hiroshi Kawada et al, Tokai J Exp Clin Med., 2014)
Association between Dietary Nitrate and Nitrite intake and Non-Hodgkin Lymphoma Survival
In a follow-up analysis of a population-based case-control study of Non-Hodgkin Lymphoma (NHL) in Connecticut women, the researchers from the University of Chicago in the US evaluated the association of dietary nitrate and nitrite intake with survival of NHL patients. The study did not find any association between nitrate or nitrite intake and NHL patient survival. (Briseis Aschebrook-Kilfoy et al, Nutr Cancer., 2012)
Studies associated with Diet and Risk of Non-Hodgkin Lymphoma
Association between Vegetables and Fruits Consumption and NHL
Green Leafy Vegetables and Citrus Fruits Intake and Non-Hodgkin Lymphoma survival in Connecticut women
A study done by the researchers from Yale University, New Haven in the United States evaluated the association between vegetable and fruit consumption and Non-Hodgkin Lymphoma survival in Connecticut women. The study used data from 568 female Non-Hodgkin Lymphoma patients who were diagnosed between 1996 and 2000 in Connecticut and was followed up for an average of 7.7 years. (Xuesong Han et al, Leuk Lymphoma., 2010)
The study found that those who reported a high intake of vegetables before diagnosis had a better overall survival among patients with Non-Hodgkin Lymphoma who survived longer than 6 months.The study highlighted that high intakes of green leafy vegetables and citrus fruits were associated with 29% and 27% reduced risk of death, respectively. Hence, increasing vegetable and citrus fruit consumption may help improve survival in NHL patients.
Impact of Vegetables and Fruits Intake on the Risk of Non-Hodgkin Lymphoma
Researchers from Soochow University in China did a meta-analysis of different observational studies obtained through literature search in the PubMed database from January 1966 to September 2012 to evaluate the association of intake of vegetables and fruits with the risk of Non-Hodgkin Lymphoma. The analysis of case-control, cohort and all studies found a 25%, 10% and 19% reduced risk of Non-Hodgkin Lymphoma, respectively, in those with very high vegetable intake compared to those with low intake of vegetables. This impact was significant in diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma, but not small lymphocytic lymphoma/chronic lymphocytic leukemia. When they analyzed the impact of intake of both fruits and vegetables together, they found a 22% reduced risk of NHL. Based on the findings from this study, the researchers concluded that the consumption of vegetables alone or both vegetables and fruits, may significantly reduce the risk of NHL. (Guo-Chong Chen et al, Int J Cancer., 2013)
Impact of Dietary intake of Lutein, Zeaxanthin, Zinc and Vegetable Consumption on the Risk of Non-Hodgkin Lymphoma
A study done in 2006 by the researchers from the Mayo Clinic College of Medicine in Rochester, US evaluated the association of intake of vegetables and nutrients involved in antioxidant activities with the risk of Non-Hodgkin Lymphoma. The study used data from 1321 Non-Hodgkin Lymphoma cases and 1057 control subjects aged 20-74 y who were enrolled in a National Cancer Institute-Surveillance, Epidemiology, and End Results population-based case-control study between 1998 and 2000. (Linda E Kelemen et al, Am J Clin Nutr., 2006)
The study found those who had a higher number of weekly servings of all vegetables, green leafy vegetables and cruciferous vegetables were associated with a 42%, 41% and 38% reduced risk of Non-Hodgkin Lymphoma, respectively. The study also found that higher daily intakes of lutein and zeaxanthin, and zinc were associated with a 46% and 42% reduced risk of Non-Hodgkin Lymphoma respectively.
Association between Polyunsaturated fatty acids, Linoleic acid and Vitamin D intake and NHL Risk
Researchers from the Centro di Riferimento Oncologico in Italy evaluated the association between linoleic acid, vitamin D and other nutrient intakes and the risk of non-Hodgkin lymphoma, based on data from a hospital-based case-control study which was conducted in Italy between 1999 and 2002, involving 190 Non-Hodgkin Lymphoma cases who were aged between 18 and 84 years. (J Polesel et al, Ann Oncol., 2006)
They found that those who followed a diet rich in polyunsaturated fatty acids, linoleic acid (a type of polyunsaturated fatty acid) and vitamin D had a 40% reduced risk of developing Non-Hodgkin Lymphoma compared to those who consumed lower amounts of these items in their diet.
They also observed that the protective effect for linoleic acid and vitamin D was stronger in women than for men. Also, while increased intake of Linoleic acid was associated with a reduced risk of follicular and diffuse large B-cell lymphoma (DLBCL), the protective effect of vitamin D was more significant for follicular subtypes.
Dairy Product Consumption and the Risk of NHL
Researchers from the Medical College of Qingdao University in China did a meta-analysis of studies from 16 articles to evaluate the association between dairy product consumption and the risk of Non-Hodgkin Lymphoma. Data for the study was obtained through literature search in PubMed, Web of Science and Embase for relevant articles published up to October 2015. The study found that the risk of Non-Hodgkin Lymphoma increased by 5% and 6% for every 200 g/day increment of dairy product and milk consumption, respectively. The researchers found significant associations between the consumption of total dairy product and milk and an increased risk of diffuse large B-cell lymphoma (DLBCL).They concluded that dairy product consumption, but not yogurt, may increase the risk of NHL. (Jia Wang et al, Nutrients., 2016)
High Consumption of Proteins, Fats and Sweets and the Risk of Non-Hodgkin Lymphoma
Analysis of dietary data from a case control study including 170 Non-Hodgkin Lymphoma cases and 190 controls, by the Mashhad University of Medical Science in Iran found that those who consumed very high amounts of proteins, fats and sweets were associated with a significantly increased Non-Hodgkin Lymphoma risk. Conversely, those who consumed high amounts of vegetables and fruits were associated with a reduced risk of Non-Hodgkin Lymphoma. (Zahra Mozaheb et al, Pan Afr Med J., 2012)
This was consistent with the data published in a review done by the National Cancer Institute, Rockville in 2006. The review highlighted that while obesity and fat intake, especially saturated or animal fat, may increase the risk of Non-Hodgkin Lymphoma, intake of whole-grains and vegetables may decrease the risk. (Amanda J Cross et al, Leuk Lymphoma. 2006)
Another study done by the University of Hawaii in the US evaluated the association between dietary patterns and the risk of Non-Hodgkin Lymphoma in a Multiethnic Cohort, which included more than 215,000 Caucasians, African-Americans, Japanese-Americans, Native Hawaiians, and Latinos who were aged between 45 and 75. A total of 939 Non-Hodgkin Lymphoma cases were identified after a mean follow-up period of 10 years. The study found that Caucasian women who followed a diet rich in Vegetables had a 44% reduced risk and men who followed a diet rich in Fat and Meat had a 5 fold higher risk of follicular lymphoma. (Eva Erber et al, Leuk Lymphoma., 2009)
Association between foods with high glycemic load and risk of Non-Hodgkin Lymphoma
Evaluation of dietary data from 190 Non-Hodgkin Lymphoma patients with a mean age of 58 years and 484 patients with a mean age of 63 years with acute non-neoplastic conditions, in a multi-center case-control study by the researchers from the Centro di Riferimento Oncologico in Italy, found that very high intake of rice and pasta increased the glycemic levels (potential to increase blood sugar) and was associated with an increased risk of developing Non-Hodgkin Lymphoma. Conversely, following a diet rich in vegetables and fruits may reduce the risk of Non-Hodgkin Lymphoma. (Renato Talamini et al, Int J Cancer., 2006)
Findings from these studies suggest that intake of a diet high in vegetables (especially green leafy vegetables) and fruits (such as citrus fruits) and dietary fiber, and dietary intake of lutein, zeaxanthin, zinc and polyunsaturated fatty acids including linoleic acid may significantly decrease the risk of Non-Hodgkin Lymphoma. However, intake of diets high in animal protein, fats and dairy products may be associated with an increased risk of NHL such as Diffuse Large B Cell Lymphoma (DLBCL). Different studies also indicated that using Vitamin D supplements in Non-Hodgkin lymphoma patients with Vitamin D deficiency may be possibly beneficial in improving treatment/clinical outcomes. Also, while intake of Selenium and Vitamin C supplements may have certain benefits such as reducing infection and inflammation respectively, in Non-Hodgkin lymphoma patients undergoing cancer treatment, including nitrate and nitrite supplements in the diet may not be beneficial for these lymphoma patients.
Cancer patients often have to deal with different chemotherapy side effects which affect their quality of life and look out for alternative therapies for cancer. Taking the right nutrition and supplements based on scientific considerations (avoiding guesswork and random selection) is the best natural remedy for cancer and treatment related side-effects.